var bibbase_data = {"data":"<img src=\"//bibbase.org/img/ajax-loader.gif\" id=\"spinner\"\n  style=\"display: none;\" alt=\"Loading..\" />\n\n<div id=\"bibbase\">\n\n  <script type=\"text/javascript\">\n    var bibbase = {\n      params: {\"bib\":\"https://raw.githubusercontent.com/jansenjfa1/bibbase.github.io/master/highlights.bib\",\"group0\":\"keyword\",\"folding\":\"1\",\"nocache\":\"1\",\"jsonp\":\"1\",\"host\":\"bibbase.org\"},\n      data: [{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[\"van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Osch\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus\",\"journal\":\"Sci Rep\",\"volume\":\"6\",\"number\":\"1\",\"pages\":\"10\",\"issn\":\"2045-2322 (Electronic) 2045-2322 (Linking)\",\"abstract\":\"We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.\",\"doi\":\"10.1038/s41598-016-0003-6\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\",\"year\":\"2016\",\"keywords\":\"a) Type 2 Diabetes Mellitus, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN41,\\n   author = {Jansen, J. F. and van Bussel, F. C. and van de Haar, H. J. and van Osch, M. J. and Hofman, P. A. and van Boxtel, M. P. and van Oostenbrugge, R. J. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Backes, W. H.},\\n   title = {Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus},\\n   journal = {Sci Rep},\\n   volume = {6},\\n   number = {1},\\n   pages = {10},\\n   ISSN = {2045-2322 (Electronic)\\n2045-2322 (Linking)},\\n   Abstract = {We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.},\\n   DOI = {10.1038/s41598-016-0003-6},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27920431},\\n   year = {2016},\\n   keywords = {a) Type 2 Diabetes Mellitus, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\\n\",\"author_short\":[\"Jansen, J. F.\",\"van Bussel, F. C.\",\"van de Haar, H. J.\",\"van Osch, M. J.\",\"Hofman, P. A.\",\"van Boxtel, M. P.\",\"van Oostenbrugge, R. J.\",\"Schram, M. T.\",\"Stehouwer, C. D.\",\"Wildberger, J. E.\",\"Backes, W. H.\"],\"key\":\"RN41\",\"id\":\"RN41\",\"bibbaseid\":\"jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Puts\"],\"firstnames\":[\"N.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Edden\"],\"firstnames\":[\"R.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning\",\"journal\":\"Medicine (Baltimore)\",\"volume\":\"95\",\"number\":\"36\",\"pages\":\"e4803\",\"issn\":\"1536-5964 (Electronic) 0025-7974 (Linking)\",\"abstract\":\"Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.\",\"doi\":\"10.1097/MD.0000000000004803\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\",\"year\":\"2016\",\"keywords\":\"a) Type 2 Diabetes Mellitus, e) Neurotransmitter MR Spectroscopy\",\"bibtex\":\"@article{RN65,\\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and Puts, N. A. and Edden, R. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\\n   title = {Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning},\\n   journal = {Medicine (Baltimore)},\\n   volume = {95},\\n   number = {36},\\n   pages = {e4803},\\n   ISSN = {1536-5964 (Electronic)\\n0025-7974 (Linking)},\\n   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.},\\n   DOI = {10.1097/MD.0000000000004803},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27603392},\\n   year = {2016},\\n   keywords = {cognition, functional MRI, magnetic resonance imaging, multiparametric MRI, type 2 diabetes mellitus},\\n   keywords = {a) Type 2 Diabetes Mellitus, e) Neurotransmitter MR Spectroscopy},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Bussel, F. C.\",\"Backes, W. H.\",\"Hofman, P. A.\",\"Puts, N. A.\",\"Edden, R. A.\",\"van Boxtel, M. P.\",\"Schram, M. T.\",\"Stehouwer, C. D.\",\"Wildberger, J. E.\",\"Jansen, J. F.\"],\"key\":\"RN65\",\"id\":\"RN65\",\"bibbaseid\":\"vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\",\"e) Neurotransmitter MR Spectroscopy\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements\",\"journal\":\"J Neuroendocrinol\",\"volume\":\"28\",\"number\":\"3\",\"pages\":\"12366\",\"issn\":\"1365-2826 (Electronic) 0953-8194 (Linking)\",\"abstract\":\"Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.\",\"doi\":\"10.1111/jne.12366\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\",\"year\":\"2016\",\"keywords\":\"a) Type 2 Diabetes Mellitus, g) Brain Connectivity\",\"bibtex\":\"@article{RN66,\\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\\n   title = {Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements},\\n   journal = {J Neuroendocrinol},\\n   volume = {28},\\n   number = {3},\\n   pages = {12366},\\n   ISSN = {1365-2826 (Electronic)\\n0953-8194 (Linking)},\\n   Abstract = {Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.},\\n   DOI = {10.1111/jne.12366},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/26791354},\\n   year = {2016},\\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Bussel, F. C.\",\"Backes, W. H.\",\"Hofman, P. A.\",\"van Boxtel, M. P.\",\"Schram, M. T.\",\"Stehouwer, C. D.\",\"Wildberger, J. E.\",\"Jansen, J. F.\"],\"key\":\"RN66\",\"id\":\"RN66\",\"bibbaseid\":\"vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kessels\"],\"firstnames\":[\"A.\",\"G.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes\",\"journal\":\"Diabetes Care\",\"volume\":\"38\",\"number\":\"5\",\"pages\":\"876-82\",\"issn\":\"1935-5548 (Electronic) 0149-5992 (Linking)\",\"abstract\":\"OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.\",\"doi\":\"10.2337/dc14-2043\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\",\"year\":\"2015\",\"keywords\":\"a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN67,\\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Oostenbrugge, R. J. and Kessels, A. G. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\\n   title = {On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes},\\n   journal = {Diabetes Care},\\n   volume = {38},\\n   number = {5},\\n   pages = {876-82},\\n   ISSN = {1935-5548 (Electronic)\\n0149-5992 (Linking)},\\n   Abstract = {OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.},\\n   DOI = {10.2337/dc14-2043},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25690006},\\n   year = {2015},\\n   keywords = {a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Bussel, F. C.\",\"Backes, W. H.\",\"Hofman, P. A.\",\"van Oostenbrugge, R. J.\",\"Kessels, A. G.\",\"van Boxtel, M. P.\",\"Schram, M. T.\",\"Stehouwer, C. D.\",\"Wildberger, J. E.\",\"Jansen, J. F.\"],\"key\":\"RN67\",\"id\":\"RN67\",\"bibbaseid\":\"vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\",\"f) Advanced Diffusion Models\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sep\"],\"firstnames\":[\"S.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Dagnelie\"],\"firstnames\":[\"P.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schaper\"],\"firstnames\":[\"N.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study\",\"journal\":\"Diabetes\",\"volume\":\"65\",\"number\":\"8\",\"pages\":\"2404-13\",\"issn\":\"1939-327X (Electronic) 0012-1797 (Linking)\",\"abstract\":\"Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.\",\"doi\":\"10.2337/db16-0128\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\",\"year\":\"2016\",\"keywords\":\"a) Type 2 Diabetes Mellitus, g) Brain Connectivity\",\"bibtex\":\"@article{RN68,\\n   author = {van Bussel, F. C. and Backes, W. H. and van Veenendaal, T. M. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Sep, S. J. and Dagnelie, P. C. and Schaper, N. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\\n   title = {Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study},\\n   journal = {Diabetes},\\n   volume = {65},\\n   number = {8},\\n   pages = {2404-13},\\n   ISSN = {1939-327X (Electronic)\\n0012-1797 (Linking)},\\n   Abstract = {Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.},\\n   DOI = {10.2337/db16-0128},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27217484},\\n   year = {2016},\\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Bussel, F. C.\",\"Backes, W. H.\",\"van Veenendaal, T. M.\",\"Hofman, P. A.\",\"van Boxtel, M. P.\",\"Schram, M. T.\",\"Sep, S. J.\",\"Dagnelie, P. C.\",\"Schaper, N.\",\"Stehouwer, C. D.\",\"Wildberger, J. E.\",\"Jansen, J. F.\"],\"key\":\"RN68\",\"id\":\"RN68\",\"bibbaseid\":\"vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\",\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verhey\"],\"firstnames\":[\"F.\",\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Steinbusch\"],\"firstnames\":[\"H.\",\"W.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging\",\"journal\":\"Front Neurosci\",\"volume\":\"11\",\"pages\":\"188\",\"issn\":\"1662-4548 (Print) 1662-453X (Linking)\",\"abstract\":\"Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.\",\"doi\":\"10.3389/fnins.2017.00188\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/28424581\",\"year\":\"2017\",\"keywords\":\"a) Type 2 Diabetes Mellitus\",\"bibtex\":\"@article{RN70,\\n   author = {van Bussel, F. C. G. and Backes, W. H. and Hofman, P. A. M. and van Oostenbrugge, R. J. and van Boxtel, M. P. J. and Verhey, F. R. J. and Steinbusch, H. W. M. and Schram, M. T. and Stehouwer, C. D. A. and Wildberger, J. E. and Jansen, J. F. A.},\\n   title = {Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging},\\n   journal = {Front Neurosci},\\n   volume = {11},\\n   pages = {188},\\n   ISSN = {1662-4548 (Print)\\n1662-453X (Linking)},\\n   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.},\\n   DOI = {10.3389/fnins.2017.00188},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28424581},\\n   year = {2017},\\n   keywords = {a) Type 2 Diabetes Mellitus},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Bussel, F. C. G.\",\"Backes, W. H.\",\"Hofman, P. A. M.\",\"van Oostenbrugge, R. J.\",\"van Boxtel, M. P. J.\",\"Verhey, F. R. J.\",\"Steinbusch, H. W. M.\",\"Schram, M. T.\",\"Stehouwer, C. D. A.\",\"Wildberger, J. E.\",\"Jansen, J. F. A.\"],\"key\":\"RN70\",\"id\":\"RN70\",\"bibbaseid\":\"vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/28424581\"},\"keyword\":[\"a) Type 2 Diabetes Mellitus\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Tse\"],\"firstnames\":[\"D.\",\"H.\",\"Y.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Scheenen\"],\"firstnames\":[\"T.\",\"W.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Klomp\"],\"firstnames\":[\"D.\",\"W.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rouhl\"],\"firstnames\":[\"R.\",\"P.\",\"W.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\",\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy\",\"journal\":\"Neuroimage Clin\",\"volume\":\"19\",\"pages\":\"47-55\",\"issn\":\"2213-1582 (Electronic) 2213-1582 (Linking)\",\"abstract\":\"The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.\",\"doi\":\"10.1016/j.nicl.2018.04.006\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\",\"year\":\"2018\",\"keywords\":\"b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity\",\"bibtex\":\"@article{RN83,\\n   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},\\n   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},\\n   journal = {Neuroimage Clin},\\n   volume = {19},\\n   pages = {47-55},\\n   ISSN = {2213-1582 (Electronic)\\n2213-1582 (Linking)},\\n   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.},\\n   DOI = {10.1016/j.nicl.2018.04.006},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},\\n   year = {2018},\\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Veenendaal, T. M.\",\"Backes, W. H.\",\"Tse, D. H. Y.\",\"Scheenen, T. W. J.\",\"Klomp, D. W.\",\"Hofman, P. A. M.\",\"Rouhl, R. P. W.\",\"Vlooswijk, M. C. G.\",\"Aldenkamp, A. P.\",\"Jansen, J. F. A.\"],\"key\":\"RN83\",\"id\":\"RN83\",\"bibbaseid\":\"vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"},\"keyword\":[\"b) Epilepsy\",\"e) Neurotransmitter MR Spectroscopy\",\"i) High Field MR\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":1,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"DM\"],\"firstnames\":[\"I.\",\"Jff\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rouhl\"],\"firstnames\":[\"R.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Louw\"],\"firstnames\":[\"A.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review\",\"journal\":\"Neurosci Biobehav Rev\",\"volume\":\"59\",\"pages\":\"92-9\",\"issn\":\"1873-7528 (Electronic) 0149-7634 (Linking)\",\"abstract\":\"As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.\",\"doi\":\"10.1016/j.neubiorev.2015.10.004\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/26475992\",\"year\":\"2015\",\"keywords\":\"b) Epilepsy\",\"bibtex\":\"@article{RN85,\\n   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Hofman, P. A. and Vlooswijk, M. C. and Rouhl, R. P. and de Louw, A. J. and Backes, W. H. and Jansen, J. F.},\\n   title = {Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review},\\n   journal = {Neurosci Biobehav Rev},\\n   volume = {59},\\n   pages = {92-9},\\n   ISSN = {1873-7528 (Electronic)\\n0149-7634 (Linking)},\\n   Abstract = {As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.},\\n   DOI = {10.1016/j.neubiorev.2015.10.004},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/26475992},\\n   year = {2015},\\n   keywords = {b) Epilepsy},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Veenendaal, T. M.\",\"DM, I. J.\",\"Aldenkamp, A. P.\",\"Hofman, P. A.\",\"Vlooswijk, M. C.\",\"Rouhl, R. P.\",\"de Louw, A. J.\",\"Backes, W. H.\",\"Jansen, J. F.\"],\"key\":\"RN85\",\"id\":\"RN85\",\"bibbaseid\":\"vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/26475992\"},\"keyword\":[\"b) Epilepsy\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"DM\"],\"firstnames\":[\"I.\",\"Jff\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lazeron\"],\"firstnames\":[\"R.\",\"H.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Puts\"],\"firstnames\":[\"N.\",\"A.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Edden\"],\"firstnames\":[\"R.\",\"A.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Louw\"],\"firstnames\":[\"A.\",\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Glutamate concentrations vary with antiepileptic drug use and mental slowing\",\"journal\":\"Epilepsy Behav\",\"volume\":\"64\",\"number\":\"Pt A\",\"pages\":\"200-205\",\"issn\":\"1525-5069 (Electronic) 1525-5050 (Linking)\",\"abstract\":\"OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.\",\"doi\":\"10.1016/j.yebeh.2016.08.027\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\",\"year\":\"2016\",\"keywords\":\"b) Epilepsy, e) Neurotransmitter MR Spectroscopy\",\"bibtex\":\"@article{RN87,\\n   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Lazeron, R. H. C. and Puts, N. A. J. and Edden, R. A. E. and Hofman, P. A. M. and de Louw, A. J. A. and Backes, W. H. and Jansen, J. F. A.},\\n   title = {Glutamate concentrations vary with antiepileptic drug use and mental slowing},\\n   journal = {Epilepsy Behav},\\n   volume = {64},\\n   number = {Pt A},\\n   pages = {200-205},\\n   ISSN = {1525-5069 (Electronic)\\n1525-5050 (Linking)},\\n   Abstract = {OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.},\\n   DOI = {10.1016/j.yebeh.2016.08.027},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27744245},\\n   year = {2016},\\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Veenendaal, T. M.\",\"DM, I. J.\",\"Aldenkamp, A. P.\",\"Lazeron, R. H. C.\",\"Puts, N. A. J.\",\"Edden, R. A. E.\",\"Hofman, P. A. M.\",\"de Louw, A. J. A.\",\"Backes, W. H.\",\"Jansen, J. F. A.\"],\"key\":\"RN87\",\"id\":\"RN87\",\"bibbaseid\":\"vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\"},\"keyword\":[\"b) Epilepsy\",\"e) Neurotransmitter MR Spectroscopy\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Krom\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Majoie\"],\"firstnames\":[\"H.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]}],\"title\":\"Functional MRI in chronic epilepsy: associations with cognitive impairment\",\"journal\":\"Lancet Neurol\",\"volume\":\"9\",\"number\":\"10\",\"pages\":\"1018-27\",\"issn\":\"1474-4465 (Electronic) 1474-4422 (Linking)\",\"abstract\":\"Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.\",\"doi\":\"10.1016/S1474-4422(10)70180-0\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\",\"year\":\"2010\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN90,\\n   author = {Vlooswijk, M. C. and Jansen, J. F. and de Krom, M. C. and Majoie, H. M. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P.},\\n   title = {Functional MRI in chronic epilepsy: associations with cognitive impairment},\\n   journal = {Lancet Neurol},\\n   volume = {9},\\n   number = {10},\\n   pages = {1018-27},\\n   ISSN = {1474-4465 (Electronic)\\n1474-4422 (Linking)},\\n   Abstract = {Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.},\\n   DOI = {10.1016/S1474-4422(10)70180-0},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20708970},\\n   year = {2010},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Vlooswijk, M. C.\",\"Jansen, J. F.\",\"de Krom, M. C.\",\"Majoie, H. M.\",\"Hofman, P. A.\",\"Backes, W. H.\",\"Aldenkamp, A. P.\"],\"key\":\"RN90\",\"id\":\"RN90\",\"bibbaseid\":\"vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"C.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Majoie\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Krom\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Memory processes and prefrontal network dysfunction in cryptogenic epilepsy\",\"journal\":\"Epilepsia\",\"volume\":\"52\",\"number\":\"8\",\"pages\":\"1467-75\",\"issn\":\"1528-1167 (Electronic) 0013-9580 (Linking)\",\"abstract\":\"PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.\",\"doi\":\"10.1111/j.1528-1167.2011.03108.x\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\",\"year\":\"2011\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN91,\\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Jeukens, C. R. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\\n   title = {Memory processes and prefrontal network dysfunction in cryptogenic epilepsy},\\n   journal = {Epilepsia},\\n   volume = {52},\\n   number = {8},\\n   pages = {1467-75},\\n   ISSN = {1528-1167 (Electronic)\\n0013-9580 (Linking)},\\n   Abstract = {PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.},\\n   DOI = {10.1111/j.1528-1167.2011.03108.x},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21635235},\\n   year = {2011},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Vlooswijk, M. C.\",\"Jansen, J. F.\",\"Jeukens, C. R.\",\"Majoie, H. J.\",\"Hofman, P. A.\",\"de Krom, M. C.\",\"Aldenkamp, A. P.\",\"Backes, W. H.\"],\"key\":\"RN91\",\"id\":\"RN91\",\"bibbaseid\":\"vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Majoie\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Krom\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Functional connectivity and language impairment in cryptogenic localization-related epilepsy\",\"journal\":\"Neurology\",\"volume\":\"75\",\"number\":\"5\",\"pages\":\"395-402\",\"issn\":\"1526-632X (Electronic) 0028-3878 (Linking)\",\"abstract\":\"BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.\",\"doi\":\"10.1212/WNL.0b013e3181ebdd3e\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\",\"year\":\"2010\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN92,\\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\\n   title = {Functional connectivity and language impairment in cryptogenic localization-related epilepsy},\\n   journal = {Neurology},\\n   volume = {75},\\n   number = {5},\\n   pages = {395-402},\\n   ISSN = {1526-632X (Electronic)\\n0028-3878 (Linking)},\\n   Abstract = {BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.},\\n   DOI = {10.1212/WNL.0b013e3181ebdd3e},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20679633},\\n   year = {2010},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\",\"author_short\":[\"Vlooswijk, M. C.\",\"Jansen, J. F.\",\"Majoie, H. J.\",\"Hofman, P. A.\",\"de Krom, M. C.\",\"Aldenkamp, A. P.\",\"Backes, W. H.\"],\"key\":\"RN92\",\"id\":\"RN92\",\"bibbaseid\":\"vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vaessen\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Krom\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Majoie\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Loss of network efficiency associated with cognitive decline in chronic epilepsy\",\"journal\":\"Neurology\",\"volume\":\"77\",\"number\":\"10\",\"pages\":\"938-44\",\"issn\":\"1526-632X (Electronic) 0028-3878 (Linking)\",\"abstract\":\"OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.\",\"doi\":\"10.1212/WNL.0b013e31822cfc2f\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\",\"year\":\"2011\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN94,\\n   author = {Vlooswijk, M. C. and Vaessen, M. J. and Jansen, J. F. and de Krom, M. C. and Majoie, H. J. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\\n   title = {Loss of network efficiency associated with cognitive decline in chronic epilepsy},\\n   journal = {Neurology},\\n   volume = {77},\\n   number = {10},\\n   pages = {938-44},\\n   ISSN = {1526-632X (Electronic)\\n0028-3878 (Linking)},\\n   Abstract = {OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.},\\n   DOI = {10.1212/WNL.0b013e31822cfc2f},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21832213},\\n   year = {2011},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Vlooswijk, M. C.\",\"Vaessen, M. J.\",\"Jansen, J. F.\",\"de Krom, M. C.\",\"Majoie, H. J.\",\"Hofman, P. A.\",\"Aldenkamp, A. P.\",\"Backes, W. H.\"],\"key\":\"RN94\",\"id\":\"RN94\",\"bibbaseid\":\"vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\",\"der\"],\"lastnames\":[\"Kruijs\"],\"firstnames\":[\"S.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bodde\"],\"firstnames\":[\"N.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vaessen\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lazeron\"],\"firstnames\":[\"R.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vonck\"],\"firstnames\":[\"K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Boon\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures\",\"journal\":\"J Neurol Neurosurg Psychiatry\",\"volume\":\"83\",\"number\":\"3\",\"pages\":\"239-47\",\"issn\":\"1468-330X (Electronic) 0022-3050 (Linking)\",\"abstract\":\"INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).\",\"doi\":\"10.1136/jnnp-2011-300776\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\",\"year\":\"2012\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN79,\\n   author = {van der Kruijs, S. J. and Bodde, N. M. and Vaessen, M. J. and Lazeron, R. H. and Vonck, K. and Boon, P. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F.},\\n   title = {Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures},\\n   journal = {J Neurol Neurosurg Psychiatry},\\n   volume = {83},\\n   number = {3},\\n   pages = {239-47},\\n   ISSN = {1468-330X (Electronic)\\n0022-3050 (Linking)},\\n   Abstract = {INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).},\\n   DOI = {10.1136/jnnp-2011-300776},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22056967},\\n   year = {2012},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van der Kruijs, S. J.\",\"Bodde, N. M.\",\"Vaessen, M. J.\",\"Lazeron, R. H.\",\"Vonck, K.\",\"Boon, P.\",\"Hofman, P. A.\",\"Backes, W. H.\",\"Aldenkamp, A. P.\",\"Jansen, J. F.\"],\"key\":\"RN79\",\"id\":\"RN79\",\"bibbaseid\":\"vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vaessen\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vlooswijk\"],\"firstnames\":[\"M.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Majoie\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"White matter network abnormalities are associated with cognitive decline in chronic epilepsy\",\"journal\":\"Cereb Cortex\",\"volume\":\"22\",\"number\":\"9\",\"pages\":\"2139-47\",\"issn\":\"1460-2199 (Electronic) 1047-3211 (Linking)\",\"abstract\":\"Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.\",\"doi\":\"10.1093/cercor/bhr298\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\",\"year\":\"2012\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN64,\\n   author = {Vaessen, M. J. and Jansen, J. F. and Vlooswijk, M. C. and Hofman, P. A. and Majoie, H. J. and Aldenkamp, A. P. and Backes, W. H.},\\n   title = {White matter network abnormalities are associated with cognitive decline in chronic epilepsy},\\n   journal = {Cereb Cortex},\\n   volume = {22},\\n   number = {9},\\n   pages = {2139-47},\\n   ISSN = {1460-2199 (Electronic)\\n1047-3211 (Linking)},\\n   Abstract = {Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.},\\n   DOI = {10.1093/cercor/bhr298},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22038907},\\n   year = {2012},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\\n\",\"author_short\":[\"Vaessen, M. J.\",\"Jansen, J. F.\",\"Vlooswijk, M. C.\",\"Hofman, P. A.\",\"Majoie, H. J.\",\"Aldenkamp, A. P.\",\"Backes, W. H.\"],\"key\":\"RN64\",\"id\":\"RN64\",\"bibbaseid\":\"vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vaessen\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Braakman\"],\"firstnames\":[\"H.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Heerink\"],\"firstnames\":[\"J.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Debeij-van\",\"Hall\"],\"firstnames\":[\"M.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy\",\"journal\":\"Cereb Cortex\",\"volume\":\"23\",\"number\":\"8\",\"pages\":\"1997-2006\",\"issn\":\"1460-2199 (Electronic) 1047-3211 (Linking)\",\"abstract\":\"Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.\",\"doi\":\"10.1093/cercor/bhs186\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\",\"year\":\"2013\",\"keywords\":\"b) Epilepsy, g) Brain Connectivity\",\"bibtex\":\"@article{RN61,\\n   author = {Vaessen, M. J. and Braakman, H. M. and Heerink, J. S. and Jansen, J. F. and Debeij-van Hall, M. H. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\\n   title = {Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy},\\n   journal = {Cereb Cortex},\\n   volume = {23},\\n   number = {8},\\n   pages = {1997-2006},\\n   ISSN = {1460-2199 (Electronic)\\n1047-3211 (Linking)},\\n   Abstract = {Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.},\\n   DOI = {10.1093/cercor/bhs186},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22772649},\\n   year = {2013},\\n   keywords = {b) Epilepsy, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Vaessen, M. J.\",\"Braakman, H. M.\",\"Heerink, J. S.\",\"Jansen, J. F.\",\"Debeij-van Hall, M. H.\",\"Hofman, P. A.\",\"Aldenkamp, A. P.\",\"Backes, W. H.\"],\"key\":\"RN61\",\"id\":\"RN61\",\"bibbaseid\":\"vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\"},\"keyword\":[\"b) Epilepsy\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Burgmans\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verhey\"],\"firstnames\":[\"F.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Blood-brain barrier impairment in dementia: current and future in vivo assessments\",\"journal\":\"Neurosci Biobehav Rev\",\"volume\":\"49\",\"pages\":\"71-81\",\"issn\":\"1873-7528 (Electronic) 0149-7634 (Linking)\",\"abstract\":\"Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.\",\"doi\":\"10.1016/j.neubiorev.2014.11.022\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\",\"year\":\"2015\",\"keywords\":\"c) Alzheimer's Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN71,\\n   author = {van de Haar, H. J. and Burgmans, S. and Hofman, P. A. and Verhey, F. R. and Jansen, J. F. and Backes, W. H.},\\n   title = {Blood-brain barrier impairment in dementia: current and future in vivo assessments},\\n   journal = {Neurosci Biobehav Rev},\\n   volume = {49},\\n   pages = {71-81},\\n   ISSN = {1873-7528 (Electronic)\\n0149-7634 (Linking)},\\n   Abstract = {Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.},\\n   DOI = {10.1016/j.neubiorev.2014.11.022},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25524876},\\n   year = {2015},\\n   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van de Haar, H. J.\",\"Burgmans, S.\",\"Hofman, P. A.\",\"Verhey, F. R.\",\"Jansen, J. F.\",\"Backes, W. H.\"],\"key\":\"RN71\",\"id\":\"RN71\",\"bibbaseid\":\"vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\"},\"keyword\":[\"c) Alzheimer's Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Burgmans\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Osch\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Buchem\"],\"firstnames\":[\"M.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Muller\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verhey\"],\"firstnames\":[\"F.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease\",\"journal\":\"Radiology\",\"volume\":\"281\",\"number\":\"2\",\"pages\":\"527-535\",\"issn\":\"1527-1315 (Electronic) 0033-8419 (Linking)\",\"abstract\":\"Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.\",\"doi\":\"10.1148/radiol.2016152244\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\",\"year\":\"2016\",\"keywords\":\"c) Alzheimer's Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN72,\\n   author = {van de Haar, H. J. and Burgmans, S. and Jansen, J. F. and van Osch, M. J. and van Buchem, M. A. and Muller, M. and Hofman, P. A. and Verhey, F. R. and Backes, W. H.},\\n   title = {Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease},\\n   journal = {Radiology},\\n   volume = {281},\\n   number = {2},\\n   pages = {527-535},\\n   ISSN = {1527-1315 (Electronic)\\n0033-8419 (Linking)},\\n   Abstract = {Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.},\\n   DOI = {10.1148/radiol.2016152244},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27243267},\\n   year = {2016},\\n   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\\n\\n\",\"author_short\":[\"van de Haar, H. J.\",\"Burgmans, S.\",\"Jansen, J. F.\",\"van Osch, M. J.\",\"van Buchem, M. A.\",\"Muller, M.\",\"Hofman, P. A.\",\"Verhey, F. R.\",\"Backes, W. H.\"],\"key\":\"RN72\",\"id\":\"RN72\",\"bibbaseid\":\"vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\"},\"keyword\":[\"c) Alzheimer's Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Osch\"],\"firstnames\":[\"M.\",\"J.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Buchem\"],\"firstnames\":[\"M.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Muller\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Burgmans\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verhey\"],\"firstnames\":[\"F.\",\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging\",\"journal\":\"Neurobiol Aging\",\"volume\":\"45\",\"pages\":\"190-196\",\"issn\":\"1558-1497 (Electronic) 0197-4580 (Linking)\",\"abstract\":\"The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.\",\"doi\":\"10.1016/j.neurobiolaging.2016.06.006\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\",\"year\":\"2016\",\"keywords\":\"c) Alzheimer's Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN75,\\n   author = {van de Haar, H. J. and Jansen, J. F. A. and van Osch, M. J. P. and van Buchem, M. A. and Muller, M. and Wong, S. M. and Hofman, P. A. M. and Burgmans, S. and Verhey, F. R. J. and Backes, W. H.},\\n   title = {Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging},\\n   journal = {Neurobiol Aging},\\n   volume = {45},\\n   pages = {190-196},\\n   ISSN = {1558-1497 (Electronic)\\n0197-4580 (Linking)},\\n   Abstract = {The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.},\\n   DOI = {10.1016/j.neurobiolaging.2016.06.006},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27459939},\\n   year = {2016},\\n   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van de Haar, H. J.\",\"Jansen, J. F. A.\",\"van Osch, M. J. P.\",\"van Buchem, M. A.\",\"Muller, M.\",\"Wong, S. M.\",\"Hofman, P. A. M.\",\"Burgmans, S.\",\"Verhey, F. R. J.\",\"Backes, W. H.\"],\"key\":\"RN75\",\"id\":\"RN75\",\"bibbaseid\":\"vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\"},\"keyword\":[\"c) Alzheimer's Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Van\",\"Osch\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[\"Van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response\",\"journal\":\"Radiology\",\"volume\":\"282\",\"number\":\"3\",\"pages\":\"924-25\",\"issn\":\"1527-1315 (Electronic) 0033-8419 (Linking)\",\"abstract\":\"Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). Models employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility (2). Therefore, we are happy to respond to these comments.\",\"doi\":\"10.1148/radiol.2017162578\",\"url\":\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\",\"year\":\"2017\",\"keywords\":\"c) Alzheimer's Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN3,\\n   author = {Backes, W. H. and Van Osch, M. J. and Van de Haar, H. J. and Jansen, J. F.},\\n   title = {Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response},\\n   journal = {Radiology},\\n   volume = {282},\\n   number = {3},\\n   pages = {924-25},\\n   ISSN = {1527-1315 (Electronic)\\n0033-8419 (Linking)},\\n   Abstract = {Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). \\nModels employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility\\n(2). Therefore, we are happy to respond to these comments.},\\n   DOI = {10.1148/radiol.2017162578},\\n   url = {https://pubs.rsna.org/doi/10.1148/radiol.2017162578},\\n   year = {2017},\\n   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Backes, W. H.\",\"Van Osch, M. J.\",\"Van de Haar, H. J.\",\"Jansen, J. F.\"],\"key\":\"RN3\",\"id\":\"RN3\",\"bibbaseid\":\"backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\"},\"keyword\":[\"c) Alzheimer's Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"Crlpn\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease\",\"journal\":\"AJNR Am J Neuroradiol\",\"volume\":\"39\",\"number\":\"2\",\"pages\":\"226-231\",\"issn\":\"1936-959X (Electronic) 0195-6108 (Linking)\",\"abstract\":\"BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.\",\"doi\":\"10.3174/ajnr.A5474\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\",\"year\":\"2018\",\"keywords\":\"d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN95,\\n   author = {Wong, S. M. and Backes, W. H. and Zhang, C. E. and Staals, J. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Jansen, J. F. A.},\\n   title = {On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease},\\n   journal = {AJNR Am J Neuroradiol},\\n   volume = {39},\\n   number = {2},\\n   pages = {226-231},\\n   ISSN = {1936-959X (Electronic)\\n0195-6108 (Linking)},\\n   Abstract = {BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.},\\n   DOI = {10.3174/ajnr.A5474},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29217741},\\n   year = {2018},\\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Backes, W. H.\",\"Zhang, C. E.\",\"Staals, J.\",\"van Oostenbrugge, R. J.\",\"Jeukens, C.\",\"Jansen, J. F. A.\"],\"key\":\"RN95\",\"id\":\"RN95\",\"bibbaseid\":\"wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"f) Advanced Diffusion Models\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"Crlpn\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors\",\"journal\":\"J Magn Reson Imaging\",\"volume\":\"46\",\"number\":\"1\",\"pages\":\"159-166\",\"issn\":\"1522-2586 (Electronic) 1053-1807 (Linking)\",\"abstract\":\"PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) </=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV </=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P < 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P < 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.\",\"doi\":\"10.1002/jmri.25540\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\",\"year\":\"2017\",\"keywords\":\"d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN96,\\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Staals, J. and Hofman, P. A. M. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Backes, W. H.},\\n   title = {Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors},\\n   journal = {J Magn Reson Imaging},\\n   volume = {46},\\n   number = {1},\\n   pages = {159-166},\\n   ISSN = {1522-2586 (Electronic)\\n1053-1807 (Linking)},\\n   Abstract = {PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) </=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV </=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P < 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P < 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.},\\n   DOI = {10.1002/jmri.25540},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28160347},\\n   year = {2017},\\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Jansen, J. F. A.\",\"Zhang, C. E.\",\"Staals, J.\",\"Hofman, P. A. M.\",\"van Oostenbrugge, R. J.\",\"Jeukens, C.\",\"Backes, W. H.\"],\"key\":\"RN96\",\"id\":\"RN96\",\"bibbaseid\":\"wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"C.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging\",\"journal\":\"Neuroimage Clin\",\"volume\":\"14\",\"pages\":\"216-221\",\"issn\":\"2213-1582 (Electronic) 2213-1582 (Linking)\",\"abstract\":\"INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.\",\"doi\":\"10.1016/j.nicl.2017.01.017\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\",\"year\":\"2017\",\"keywords\":\"d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN97,\\n   author = {Wong, S. M. and Zhang, C. E. and van Bussel, F. C. and Staals, J. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H. and Jansen, J. F.},\\n   title = {Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging},\\n   journal = {Neuroimage Clin},\\n   volume = {14},\\n   pages = {216-221},\\n   ISSN = {2213-1582 (Electronic)\\n2213-1582 (Linking)},\\n   Abstract = {INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.},\\n   DOI = {10.1016/j.nicl.2017.01.017},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28180080},\\n   year = {2017},\\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Zhang, C. E.\",\"van Bussel, F. C.\",\"Staals, J.\",\"Jeukens, C. R.\",\"Hofman, P. A.\",\"van Oostenbrugge, R. J.\",\"Backes, W. H.\",\"Jansen, J. F.\"],\"key\":\"RN97\",\"id\":\"RN97\",\"bibbaseid\":\"wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"f) Advanced Diffusion Models\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Uiterwijk\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"Crlpn\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]}],\"title\":\"Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging\",\"journal\":\"Brain Imaging Behav\",\"issn\":\"1931-7565 (Electronic) 1931-7557 (Linking)\",\"abstract\":\"Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.\",\"doi\":\"10.1007/s11682-018-9855-7\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\",\"year\":\"2018\",\"keywords\":\"d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN98,\\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Backes, W. H. and Jansen, J. F. A. and Jeukens, Crlpn and van Oostenbrugge, R. J. and Staals, J.},\\n   title = {Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging},\\n   journal = {Brain Imaging Behav},\\n   ISSN = {1931-7565 (Electronic)\\n1931-7557 (Linking)},\\n   Abstract = {Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.},\\n   DOI = {10.1007/s11682-018-9855-7},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29572621},\\n   year = {2018},\\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Zhang, C. E.\",\"Wong, S. M.\",\"Uiterwijk, R.\",\"Backes, W. H.\",\"Jansen, J. F. A.\",\"Jeukens, C.\",\"van Oostenbrugge, R. J.\",\"Staals, J.\"],\"key\":\"RN98\",\"id\":\"RN98\",\"bibbaseid\":\"zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Uiterwijk\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hoff\"],\"firstnames\":[\"E.\",\"I.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schreuder\"],\"firstnames\":[\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"C.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]}],\"title\":\"Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition\",\"journal\":\"Stroke\",\"volume\":\"48\",\"number\":\"3\",\"pages\":\"658-663\",\"issn\":\"1524-4628 (Electronic) 0039-2499 (Linking)\",\"abstract\":\"BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.\",\"doi\":\"10.1161/STROKEAHA.116.015084\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\",\"year\":\"2017\",\"keywords\":\"d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN99,\\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Staals, J. and Backes, W. H. and Hoff, E. I. and Schreuder, T. and Jeukens, C. R. and Jansen, J. F. and van Oostenbrugge, R. J.},\\n   title = {Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition},\\n   journal = {Stroke},\\n   volume = {48},\\n   number = {3},\\n   pages = {658-663},\\n   ISSN = {1524-4628 (Electronic)\\n0039-2499 (Linking)},\\n   Abstract = {BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.},\\n   DOI = {10.1161/STROKEAHA.116.015084},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28196940},\\n   year = {2017},\\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Zhang, C. E.\",\"Wong, S. M.\",\"Uiterwijk, R.\",\"Staals, J.\",\"Backes, W. H.\",\"Hoff, E. I.\",\"Schreuder, T.\",\"Jeukens, C. R.\",\"Jansen, J. F.\",\"van Oostenbrugge, R. J.\"],\"key\":\"RN99\",\"id\":\"RN99\",\"bibbaseid\":\"zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"f) Advanced Diffusion Models\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"van\",\"de\"],\"lastnames\":[\"Haar\"],\"firstnames\":[\"H.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jeukens\"],\"firstnames\":[\"C.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease\",\"journal\":\"Neurology\",\"volume\":\"88\",\"number\":\"5\",\"pages\":\"426-432\",\"issn\":\"1526-632X (Electronic) 0028-3878 (Linking)\",\"abstract\":\"OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.\",\"doi\":\"10.1212/WNL.0000000000003556\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\",\"year\":\"2017\",\"keywords\":\"d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN100,\\n   author = {Zhang, C. E. and Wong, S. M. and van de Haar, H. J. and Staals, J. and Jansen, J. F. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H.},\\n   title = {Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease},\\n   journal = {Neurology},\\n   volume = {88},\\n   number = {5},\\n   pages = {426-432},\\n   ISSN = {1526-632X (Electronic)\\n0028-3878 (Linking)},\\n   Abstract = {OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.},\\n   DOI = {10.1212/WNL.0000000000003556},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28031395},\\n   year = {2017},\\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\",\"author_short\":[\"Zhang, C. E.\",\"Wong, S. M.\",\"van de Haar, H. J.\",\"Staals, J.\",\"Jansen, J. F.\",\"Jeukens, C. R.\",\"Hofman, P. A.\",\"van Oostenbrugge, R. J.\",\"Backes, W. H.\"],\"key\":\"RN100\",\"id\":\"RN100\",\"bibbaseid\":\"zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hoff\"],\"firstnames\":[\"E.\",\"I.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease\",\"journal\":\"Neurology\",\"volume\":\"92\",\"number\":\"15\",\"pages\":\"e1669-e1677\",\"issn\":\"1526-632X (Electronic) 0028-3878 (Linking)\",\"abstract\":\"OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.\",\"doi\":\"10.1212/WNL.0000000000007263\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\",\"year\":\"2019\",\"keywords\":\"d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN128,\\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\\n   journal = {Neurology},\\n   volume = {92},\\n   number = {15},\\n   pages = {e1669-e1677},\\n   ISSN = {1526-632X (Electronic)\\n0028-3878 (Linking)},\\n   Abstract = {OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.},\\n   DOI = {10.1212/WNL.0000000000007263},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275},\\n   year = {2019},\\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Jansen, J. F. A.\",\"Zhang, C. E.\",\"Hoff, E. I.\",\"Staals, J.\",\"van Oostenbrugge, R. J.\",\"Backes, W. H.\"],\"key\":\"RN128\",\"id\":\"RN128\",\"bibbaseid\":\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Barendse\"],\"firstnames\":[\"E.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Puts\"],\"firstnames\":[\"N.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Edden\"],\"firstnames\":[\"R.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zinger\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Thoonen\"],\"firstnames\":[\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hendriks\"],\"firstnames\":[\"M.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kessels\"],\"firstnames\":[\"R.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]}],\"title\":\"Altered neurotransmitter metabolism in adolescents with high-functioning autism\",\"journal\":\"Psychiatry Res Neuroimaging\",\"volume\":\"256\",\"pages\":\"44-49\",\"issn\":\"1872-7506 (Electronic) 0925-4927 (Linking)\",\"abstract\":\"Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy ((1)H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few (1)H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using (1)H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.\",\"doi\":\"10.1016/j.pscychresns.2016.09.007\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/27685800\",\"year\":\"2016\",\"keywords\":\"e) Neurotransmitter MR Spectroscopy\",\"bibtex\":\"@article{RN20,\\n   author = {Drenthen, G. S. and Barendse, E. M. and Aldenkamp, A. P. and van Veenendaal, T. M. and Puts, N. A. and Edden, R. A. and Zinger, S. and Thoonen, G. and Hendriks, M. P. and Kessels, R. P. and Jansen, J. F.},\\n   title = {Altered neurotransmitter metabolism in adolescents with high-functioning autism},\\n   journal = {Psychiatry Res Neuroimaging},\\n   volume = {256},\\n   pages = {44-49},\\n   ISSN = {1872-7506 (Electronic)\\n0925-4927 (Linking)},\\n   Abstract = {Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy ((1)H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few (1)H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using (1)H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.},\\n   DOI = {10.1016/j.pscychresns.2016.09.007},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27685800},\\n   year = {2016},\\n   keywords = {e) Neurotransmitter MR Spectroscopy},\\n   type = {Journal Article}\\n}\\n\",\"author_short\":[\"Drenthen, G. S.\",\"Barendse, E. M.\",\"Aldenkamp, A. P.\",\"van Veenendaal, T. M.\",\"Puts, N. A.\",\"Edden, R. A.\",\"Zinger, S.\",\"Thoonen, G.\",\"Hendriks, M. P.\",\"Kessels, R. P.\",\"Jansen, J. F.\"],\"key\":\"RN20\",\"id\":\"RN20\",\"bibbaseid\":\"drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/27685800\"},\"keyword\":[\"e) Neurotransmitter MR Spectroscopy\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\",\"drenthen,  g\":\"http://www.geralddrenthen.nl/research-2/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[\"van\"],\"lastnames\":[\"Veenendaal\"],\"firstnames\":[\"T.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Bussel\"],\"firstnames\":[\"F.\",\"C.\",\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Edden\"],\"firstnames\":[\"R.\",\"A.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Puts\"],\"firstnames\":[\"N.\",\"A.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance\",\"journal\":\"Magn Reson Imaging\",\"volume\":\"48\",\"pages\":\"107-114\",\"issn\":\"1873-5894 (Electronic) 0730-725X (Linking)\",\"abstract\":\"PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.\",\"doi\":\"10.1016/j.mri.2017.12.029\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/29306050\",\"year\":\"2018\",\"keywords\":\"e) Neurotransmitter MR Spectroscopy\",\"bibtex\":\"@article{RN84,\\n   author = {van Veenendaal, T. M. and Backes, W. H. and van Bussel, F. C. G. and Edden, R. A. E. and Puts, N. A. J. and Aldenkamp, A. P. and Jansen, J. F. A.},\\n   title = {Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance},\\n   journal = {Magn Reson Imaging},\\n   volume = {48},\\n   pages = {107-114},\\n   ISSN = {1873-5894 (Electronic)\\n0730-725X (Linking)},\\n   Abstract = {PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.},\\n   DOI = {10.1016/j.mri.2017.12.029},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29306050},\\n   year = {2018},\\n   keywords = {e) Neurotransmitter MR Spectroscopy},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"van Veenendaal, T. M.\",\"Backes, W. H.\",\"van Bussel, F. C. G.\",\"Edden, R. A. E.\",\"Puts, N. A. J.\",\"Aldenkamp, A. P.\",\"Jansen, J. F. A.\"],\"key\":\"RN84\",\"id\":\"RN84\",\"bibbaseid\":\"vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/29306050\"},\"keyword\":[\"e) Neurotransmitter MR Spectroscopy\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lu\"],\"firstnames\":[\"Y.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Mazaheri\"],\"firstnames\":[\"Y.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stambuk\"],\"firstnames\":[\"H.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Koutcher\"],\"firstnames\":[\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Shukla-Dave\"],\"firstnames\":[\"A.\"],\"suffixes\":[]}],\"title\":\"Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer\",\"journal\":\"J Magn Reson Imaging\",\"volume\":\"36\",\"number\":\"5\",\"pages\":\"1088-96\",\"issn\":\"1522-2586 (Electronic) 1053-1807 (Linking)\",\"abstract\":\"PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.\",\"doi\":\"10.1002/jmri.23770\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/22826198\",\"year\":\"2012\",\"keywords\":\"f) Advanced Diffusion Models\",\"bibtex\":\"@article{RN49,\\n   author = {Lu, Y. and Jansen, J. F. and Mazaheri, Y. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},\\n   title = {Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer},\\n   journal = {J Magn Reson Imaging},\\n   volume = {36},\\n   number = {5},\\n   pages = {1088-96},\\n   ISSN = {1522-2586 (Electronic)\\n1053-1807 (Linking)},\\n   Abstract = {PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.},\\n   DOI = {10.1002/jmri.23770},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22826198},\\n   year = {2012},\\n   keywords = {f) Advanced Diffusion Models},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Lu, Y.\",\"Jansen, J. F.\",\"Mazaheri, Y.\",\"Stambuk, H. E.\",\"Koutcher, J. A.\",\"Shukla-Dave, A.\"],\"key\":\"RN49\",\"id\":\"RN49\",\"bibbaseid\":\"lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/22826198\"},\"keyword\":[\"f) Advanced Diffusion Models\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stambuk\"],\"firstnames\":[\"H.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Koutcher\"],\"firstnames\":[\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Shukla-Dave\"],\"firstnames\":[\"A.\"],\"suffixes\":[]}],\"title\":\"Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study\",\"journal\":\"AJNR Am J Neuroradiol\",\"volume\":\"31\",\"number\":\"4\",\"pages\":\"741-8\",\"issn\":\"1936-959X (Electronic) 0195-6108 (Linking)\",\"abstract\":\"BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T. Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between K(app) and D(app). RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). D(app) was approximately twice the value of ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84). K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, K(app), potentially with added value.\",\"doi\":\"10.3174/ajnr.A1919\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/20037133\",\"year\":\"2010\",\"keywords\":\"f) Advanced Diffusion Models\",\"bibtex\":\"@article{RN40,\\n   author = {Jansen, J. F. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},\\n   title = {Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study},\\n   journal = {AJNR Am J Neuroradiol},\\n   volume = {31},\\n   number = {4},\\n   pages = {741-8},\\n   ISSN = {1936-959X (Electronic)\\n0195-6108 (Linking)},\\n   Abstract = {BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T. Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between K(app) and D(app). RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). D(app) was approximately twice the value of ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84). K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, K(app), potentially with added value.},\\n   DOI = {10.3174/ajnr.A1919},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20037133},\\n   year = {2010},\\n   keywords = {f) Advanced Diffusion Models},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Jansen, J. F.\",\"Stambuk, H. E.\",\"Koutcher, J. A.\",\"Shukla-Dave, A.\"],\"key\":\"RN40\",\"id\":\"RN40\",\"bibbaseid\":\"jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/20037133\"},\"keyword\":[\"f) Advanced Diffusion Models\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Schnerr\"],\"firstnames\":[\"R.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Uludag\"],\"firstnames\":[\"K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hofman\"],\"firstnames\":[\"P.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wildberger\"],\"firstnames\":[\"J.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect\",\"journal\":\"Front Physiol\",\"volume\":\"8\",\"pages\":\"961\",\"issn\":\"1664-042X (Print) 1664-042X (Linking)\",\"abstract\":\"Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.\",\"doi\":\"10.3389/fphys.2017.00961\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\",\"year\":\"2017\",\"keywords\":\"i) High Field MR, h) Cerebrovascular MRI\",\"bibtex\":\"@article{RN56,\\n   author = {Schnerr, R. S. and Jansen, J. F. A. and Uludag, K. and Hofman, P. A. M. and Wildberger, J. E. and van Oostenbrugge, R. J. and Backes, W. H.},\\n   title = {Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect},\\n   journal = {Front Physiol},\\n   volume = {8},\\n   pages = {961},\\n   ISSN = {1664-042X (Print)\\n1664-042X (Linking)},\\n   Abstract = {Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.},\\n   DOI = {10.3389/fphys.2017.00961},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29225580},\\n   year = {2017},\\n   keywords = {i) High Field MR, h) Cerebrovascular MRI},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Schnerr, R. S.\",\"Jansen, J. F. A.\",\"Uludag, K.\",\"Hofman, P. A. M.\",\"Wildberger, J. E.\",\"van Oostenbrugge, R. J.\",\"Backes, W. H.\"],\"key\":\"RN56\",\"id\":\"RN56\",\"bibbaseid\":\"schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\"},\"keyword\":[\"i) High Field MR\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Haast\"],\"firstnames\":[\"R.\",\"A.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ivanov\"],\"firstnames\":[\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"RJT\"],\"firstnames\":[\"I.\",\"Jsselstein\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sallevelt\"],\"firstnames\":[\"Sceh\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Smeets\"],\"firstnames\":[\"H.\",\"J.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Coo\"],\"firstnames\":[\"I.\",\"F.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Formisano\"],\"firstnames\":[\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Uludag\"],\"firstnames\":[\"K.\"],\"suffixes\":[]}],\"title\":\"Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study\",\"journal\":\"Neuroimage Clin\",\"volume\":\"18\",\"pages\":\"231-244\",\"issn\":\"2213-1582 (Electronic) 2213-1582 (Linking)\",\"abstract\":\"One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.\",\"doi\":\"10.1016/j.nicl.2018.01.017\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\",\"year\":\"2018\",\"keywords\":\"i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging\",\"bibtex\":\"@article{RN27,\\n   author = {Haast, R. A. M. and Ivanov, D. and RJT, I. Jsselstein and Sallevelt, Sceh and Jansen, J. F. A. and Smeets, H. J. M. and de Coo, I. F. M. and Formisano, E. and Uludag, K.},\\n   title = {Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study},\\n   journal = {Neuroimage Clin},\\n   volume = {18},\\n   pages = {231-244},\\n   ISSN = {2213-1582 (Electronic)\\n2213-1582 (Linking)},\\n   Abstract = {One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.},\\n   DOI = {10.1016/j.nicl.2018.01.017},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447},\\n   year = {2018},\\n   keywords = {i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Haast, R. A. M.\",\"Ivanov, D.\",\"RJT, I. J.\",\"Sallevelt, S.\",\"Jansen, J. F. A.\",\"Smeets, H. J. M.\",\"de Coo, I. F. M.\",\"Formisano, E.\",\"Uludag, K.\"],\"key\":\"RN27\",\"id\":\"RN27\",\"bibbaseid\":\"haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"},\"keyword\":[\"i) High Field MR\",\"h) Cerebrovascular MRI\",\"j) Myelin Imaging\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration\",\"journal\":\"Neuroimage\",\"volume\":\"195\",\"pages\":\"333-339\",\"issn\":\"1095-9572 (Electronic) 1053-8119 (Linking)\",\"abstract\":\"Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30min still provides an excellent reproducibility.\",\"keywords\":\"j) Myelin Imaging\",\"doi\":\"10.1016/j.neuroimage.2019.04.011\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/30965132\",\"year\":\"2019\",\"bibtex\":\"@article{RN127,\\n   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F. A.},\\n   title = {Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration},\\n   journal = {Neuroimage},\\n   volume = {195},\\n   pages = {333-339},\\n   ISSN = {1095-9572 (Electronic)\\n1053-8119 (Linking)},\\n   Abstract = {Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30min still provides an excellent reproducibility.},\\n   Keywords = {Myelin water fraction\\nReproducibility\\nT2 relaxometry},\\n   DOI = {10.1016/j.neuroimage.2019.04.011},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30965132},\\n   year = {2019},\\n   keywords = {j) Myelin Imaging},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Drenthen, G. S.\",\"Backes, W. H.\",\"Aldenkamp, A. P.\",\"Jansen, J. F. A.\"],\"key\":\"RN127\",\"id\":\"RN127\",\"bibbaseid\":\"drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/30965132\"},\"keyword\":[\"j) Myelin Imaging\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\",\"drenthen,  g\":\"http://www.geralddrenthen.nl/research-2/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Op\",\"'t\",\"Veld\"],\"firstnames\":[\"G.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit\",\"journal\":\"Magn Reson Med\",\"volume\":\"81\",\"number\":\"5\",\"pages\":\"3292-3303\",\"issn\":\"1522-2594 (Electronic) 0740-3194 (Linking)\",\"abstract\":\"PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.\",\"keywords\":\"j) Myelin Imaging\",\"doi\":\"10.1002/mrm.27600\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/30444019\",\"year\":\"2019\",\"bibtex\":\"@article{RN121,\\n   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Op 't Veld, G. J. and Jansen, J. F. A.},\\n   title = {A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit},\\n   journal = {Magn Reson Med},\\n   volume = {81},\\n   number = {5},\\n   pages = {3292-3303},\\n   ISSN = {1522-2594 (Electronic)\\n0740-3194 (Linking)},\\n   Abstract = {PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.},\\n   Keywords = {T2 relaxometry\\nmyelin water fraction\\nnonnegative least squares\\northogonal matching pursuit},\\n   DOI = {10.1002/mrm.27600},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30444019},\\n   year = {2019},\\n   keywords = {j) Myelin Imaging},\\n   type = {Journal Article}\\n}\\n\",\"author_short\":[\"Drenthen, G. S.\",\"Backes, W. H.\",\"Aldenkamp, A. P.\",\"Op 't Veld, G. J.\",\"Jansen, J. F. A.\"],\"key\":\"RN121\",\"id\":\"RN121\",\"bibbaseid\":\"drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/30444019\"},\"keyword\":[\"j) Myelin Imaging\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fonseca\",\"Wald\"],\"firstnames\":[\"E.\",\"L.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Debeij\",\"-\",\"Van\",\"Hall\"],\"firstnames\":[\"M.\",\"H.\",\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hendriksen\"],\"firstnames\":[\"J.\",\"G.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldenkamp\"],\"firstnames\":[\"A.\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Vermeulen\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Klinkenberg\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Lower myelin-water content of the frontal lobe in childhood absence epilepsy\",\"journal\":\"Epilepsia\",\"volume\":\"0\",\"number\":\"0\",\"issn\":\"0013-9580\",\"abstract\":\"Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.\",\"doi\":\"10.1111/epi.16280\",\"url\":\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\",\"year\":\"2019\",\"keywords\":\"b) Epilepsy, j) Myelin Imaging\",\"bibtex\":\"@article{RN132,\\n   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Debeij - Van Hall, M. H. J. A. and Hendriksen, J. G. M. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},\\n   title = {Lower myelin-water content of the frontal lobe in childhood absence epilepsy},\\n   journal = {Epilepsia},\\n   volume = {0},\\n   number = {0},\\n   ISSN = {0013-9580},\\n   Abstract = {Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.},\\n   DOI = {10.1111/epi.16280},\\n   url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280},\\n   year = {2019},\\n   keywords = {b) Epilepsy, j) Myelin Imaging},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Drenthen, G. S.\",\"Fonseca Wald, E. L. A.\",\"Backes, W. H.\",\"Debeij - Van Hall, M. H. J. A.\",\"Hendriksen, J. G. M.\",\"Aldenkamp, A. P.\",\"Vermeulen, R. J.\",\"Klinkenberg, S.\",\"Jansen, J. F. A.\"],\"key\":\"RN132\",\"id\":\"RN132\",\"bibbaseid\":\"drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\"},\"keyword\":[\"b) Epilepsy\",\"j) Myelin Imaging\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\",\"drenthen,  g\":\"http://www.geralddrenthen.nl/research-2/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hoff\"],\"firstnames\":[\"E.\",\"I.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]}],\"title\":\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease\",\"journal\":\"Neurology\",\"volume\":\"92\",\"number\":\"15\",\"pages\":\"e1669-e1677\",\"issn\":\"1526-632X (Electronic) 0028-3878 (Linking)\",\"doi\":\"10.1212/WNL.0000000000007263\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\",\"keywords\":\"d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI\",\"year\":\"2019\",\"bibtex\":\"@article{RN226,\\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\\n   journal = {Neurology},\\n   volume = {92},\\n   number = {15},\\n   pages = {e1669-e1677},\\n   ISSN = {1526-632X (Electronic)\\n0028-3878 (Linking)},\\n   DOI = {10.1212/WNL.0000000000007263},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275\\nhttps://n.neurology.org/content/92/15/e1669.long},\\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\\n   year = {2019},\\n   \\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Jansen, J. F. A.\",\"Zhang, C. E.\",\"Hoff, E. I.\",\"Staals, J.\",\"van Oostenbrugge, R. J.\",\"Backes, W. H.\"],\"key\":\"RN226\",\"id\":\"RN226\",\"bibbaseid\":\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"h) Cerebrovascular MRI\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Wong\"],\"firstnames\":[\"S.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zhang\"],\"firstnames\":[\"C.\",\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Voorter\"],\"firstnames\":[\"P.\",\"H.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Staals\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Oostenbrugge\"],\"firstnames\":[\"R.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease\",\"journal\":\"J Magn Reson Imaging\",\"volume\":\"51\",\"number\":\"4\",\"pages\":\"1170-1180\",\"issn\":\"1522-2586 (Electronic) 1053-1807 (Linking)\",\"doi\":\"10.1002/jmri.26920\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\",\"year\":\"2020\",\"keywords\":\"d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models\",\"bibtex\":\"@article{RN234,\\n   author = {Wong, S. M. and Backes, W. H. and Drenthen, G. S. and Zhang, C. E. and Voorter, P. H. M. and Staals, J. and van Oostenbrugge, R. J. and Jansen, J. F. A.},\\n   title = {Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease},\\n   journal = {J Magn Reson Imaging},\\n   volume = {51},\\n   number = {4},\\n   pages = {1170-1180},\\n   ISSN = {1522-2586 (Electronic)\\n1053-1807 (Linking)},\\n   DOI = {10.1002/jmri.26920},\\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31486211\\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf},\\n   year = {2020},\\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Wong, S. M.\",\"Backes, W. H.\",\"Drenthen, G. S.\",\"Zhang, C. E.\",\"Voorter, P. H. M.\",\"Staals, J.\",\"van Oostenbrugge, R. J.\",\"Jansen, J. F. A.\"],\"key\":\"RN234\",\"id\":\"RN234\",\"bibbaseid\":\"wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\"},\"keyword\":[\"d) Cerebral Small Vessel Disease\",\"f) Advanced Diffusion Models\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\",\"drenthen,  g\":\"http://www.geralddrenthen.nl/research-2/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Vingerhoets\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Tse\"],\"firstnames\":[\"D.\",\"H.\",\"Y.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Van\",\"Oudenaren\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hernaus\"],\"firstnames\":[\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Van\",\"Duin\"],\"firstnames\":[\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zinkstok\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ramaekers\"],\"firstnames\":[\"J.\",\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"McAlonan\"],\"firstnames\":[\"G.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Amelsvoort\"],\"firstnames\":[\"T.\"],\"suffixes\":[]}],\"title\":\"Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.\",\"journal\":\"J Psychopharmacol\",\"doi\":\"10.1177/0269881120922977\",\"year\":\"2020\",\"keywords\":\"e) Neurotransmitter MR Spectroscopy, i) High Field MR\",\"bibtex\":\"@article{RN247,\\n   author = {Vingerhoets, C. and Tse, D. H. Y. and Van Oudenaren, M. and Hernaus, D. and Van Duin, E. and Zinkstok, J. and Ramaekers, J. G. and Jansen, J. F. A. and McAlonan, G. and van Amelsvoort, T.},\\n   title = {Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.},\\n   journal = {J Psychopharmacol},\\n   DOI = {10.1177/0269881120922977},\\n   year = {2020},\\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Vingerhoets, C.\",\"Tse, D. H. Y.\",\"Van Oudenaren, M.\",\"Hernaus, D.\",\"Van Duin, E.\",\"Zinkstok, J.\",\"Ramaekers, J. G.\",\"Jansen, J. F. 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G.\"],\"key\":\"RN253\",\"id\":\"RN253\",\"bibbaseid\":\"mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf\"},\"keyword\":[\"e) Neurotransmitter MR Spectroscopy\",\"i) High Field MR\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":0,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"DeJong\"],\"firstnames\":[\"N.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Dagnelie\"],\"firstnames\":[\"P.\",\"C.\"],\"suffixes\":[]},{\"propositions\":[\"van\",\"der\"],\"lastnames\":[\"Kallen\"],\"firstnames\":[\"C.\",\"J.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kroon\"],\"firstnames\":[\"A.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wesselius\"],\"firstnames\":[\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Koster\"],\"firstnames\":[\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kohler\"],\"firstnames\":[\"S.\"],\"suffixes\":[]}],\"title\":\"Cognitive resilience depends on white matter connectivity: The Maastricht Study\",\"journal\":\"Alzheimers Dement\",\"issn\":\"1552-5279 (Electronic) 1552-5260 (Linking)\",\"doi\":\"10.1002/alz.12758\",\"url\":\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\",\"year\":\"2022\",\"keywords\":\"c) Alzheimer's Disease, g) Brain Connectivity\",\"bibtex\":\"@article{RN307,\\n   author = {DeJong, N. R. and Jansen, J. F. A. and van Boxtel, M. P. J. and Schram, M. T. and Stehouwer, C. D. A. and Dagnelie, P. C. and van der Kallen, C. J. H. and Kroon, A. A. and Wesselius, A. and Koster, A. and Backes, W. H. and Kohler, S.},\\n   title = {Cognitive resilience depends on white matter connectivity: The Maastricht Study},\\n   journal = {Alzheimers Dement},\\n   ISSN = {1552-5279 (Electronic)\\n1552-5260 (Linking)},\\n   DOI = {10.1002/alz.12758},\\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35920350},\\n   year = {2022},\\n   keywords = {c) Alzheimer's Disease, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"DeJong, N. R.\",\"Jansen, J. F. A.\",\"van Boxtel, M. P. J.\",\"Schram, M. T.\",\"Stehouwer, C. D. A.\",\"Dagnelie, P. C.\",\"van der Kallen, C. J. H.\",\"Kroon, A. A.\",\"Wesselius, A.\",\"Koster, A.\",\"Backes, W. H.\",\"Kohler, S.\"],\"key\":\"RN307\",\"id\":\"RN307\",\"bibbaseid\":\"dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\"},\"keyword\":[\"c) Alzheimer's Disease\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":1,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Freeze\"],\"firstnames\":[\"W.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jacobs\"],\"firstnames\":[\"H.\",\"I.\",\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verheggen\"],\"firstnames\":[\"I.\",\"C.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[\"van\"],\"lastnames\":[\"Boxtel\"],\"firstnames\":[\"M.\",\"P.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hoff\"],\"firstnames\":[\"E.\",\"I.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Verhey\"],\"firstnames\":[\"F.\",\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease\",\"journal\":\"J Alzheimers Dis\",\"issn\":\"1875-8908 (Electronic) 1387-2877 (Linking)\",\"doi\":\"10.3233/JAD-220175\",\"url\":\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\",\"year\":\"2022\",\"keywords\":\"c) Alzheimer's Disease, g) Brain Connectivity\",\"bibtex\":\"@article{RN305,\\n   author = {Drenthen, G. S. and Backes, W. H. and Freeze, W. M. and Jacobs, H. I. L. and Verheggen, I. C. M. and van Boxtel, M. P. J. and Hoff, E. I. and Verhey, F. R. and Jansen, J. F. A.},\\n   title = {Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease},\\n   journal = {J Alzheimers Dis},\\n   ISSN = {1875-8908 (Electronic)\\n1387-2877 (Linking)},\\n   DOI = {10.3233/JAD-220175},\\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35871335},\\n   year = {2022},\\n   keywords = {c) Alzheimer's Disease, g) Brain Connectivity},\\n   type = {Journal Article}\\n}\\n\\n\",\"author_short\":[\"Drenthen, G. S.\",\"Backes, W. H.\",\"Freeze, W. M.\",\"Jacobs, H. I. L.\",\"Verheggen, I. C. M.\",\"van Boxtel, M. P. J.\",\"Hoff, E. I.\",\"Verhey, F. R.\",\"Jansen, J. F. A.\"],\"key\":\"RN305\",\"id\":\"RN305\",\"bibbaseid\":\"drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\"},\"keyword\":[\"c) Alzheimer's Disease\",\"g) Brain Connectivity\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"Journal Article\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Monereo-Sanchez\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Jong\"],\"firstnames\":[\"J.\",\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Drenthen\"],\"firstnames\":[\"G.\",\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Beran\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Backes\"],\"firstnames\":[\"W.\",\"H.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Stehouwer\"],\"firstnames\":[\"C.\",\"D.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Schram\"],\"firstnames\":[\"M.\",\"T.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Linden\"],\"firstnames\":[\"D.\",\"E.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Jansen\"],\"firstnames\":[\"J.\",\"F.\",\"A.\"],\"suffixes\":[]}],\"title\":\"Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study\",\"journal\":\"Neuroimage\",\"pages\":\"118174\",\"issn\":\"1095-9572 (Electronic) 1053-8119 (Linking)\",\"doi\":\"10.1016/j.neuroimage.2021.118174\",\"url\":\"https://www.ncbi.nlm.nih.gov/pubmed/34000406\",\"year\":\"2021\",\"keywords\":\"k) MRI quality control\",\"bibtex\":\"@article{RN280,\\n   author = {Monereo-Sanchez, J. and de Jong, J. J. A. and Drenthen, G. S. and Beran, M. and Backes, W. H. and Stehouwer, C. D. A. and Schram, M. T. and Linden, D. E. J. and Jansen, J. F. A.},\\n   title = {Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study},\\n   journal = {Neuroimage},\\n   pages = {118174},\\n   ISSN = {1095-9572 (Electronic)\\n1053-8119 (Linking)},\\n   DOI = {10.1016/j.neuroimage.2021.118174},\\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/34000406},\\n   year = {2021},\\n   keywords = {k) MRI quality control},\\n   type = {Journal Article}\\n}\\n\",\"author_short\":[\"Monereo-Sanchez, J.\",\"de Jong, J. J. A.\",\"Drenthen, G. S.\",\"Beran, M.\",\"Backes, W. H.\",\"Stehouwer, C. D. A.\",\"Schram, M. T.\",\"Linden, D. E. J.\",\"Jansen, J. F. A.\"],\"key\":\"RN280\",\"id\":\"RN280\",\"bibbaseid\":\"monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.ncbi.nlm.nih.gov/pubmed/34000406\"},\"keyword\":[\"k) MRI quality control\"],\"metadata\":{\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\"downloads\":1,\"html\":\"\"}],\n      metadata: {\"owner\":\"jansen, j\",\"authorlinks\":{\"jansen, j\":\"https://www.jansenjfa.com/research/\"}},\n      ownerID: \"TEAWLnKpXtQE8hs6C\"\n    };\n  </script>\n\n  <script type=\"text/javascript\">\n  var site$;\n  if (typeof $ != 'undefined') {\n    console.log('existing jquery: storing and then restoring');\n    site$ = $;\n    $ = null;\n  }\n  </script>\n\n  <script src=\"https://ajax.googleapis.com/ajax/libs/jquery/2.2.4/jquery.min.js\">\n  </script>\n  <script type=\"text/javascript\">\n  if (site$) {\n    console.log('existing jquery: avoiding conflict and restoring');\n    bb$ = $.noConflict(true);\n    $ = site$;\n  } else {\n    bb$ = $;\n  }\n  </script>\n\n  <script src=\"//bibbase.org/js/bibbase.min.js\"\n          type=\"text/javascript\">\n  </script>\n\n  <script type=\"text/javascript\"\n          src=\"https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.1/MathJax.js?config=TeX-AMS-MML_HTMLorMML\">\n  </script>\n  <script type=\"text/x-mathjax-config\">\n    MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]},\n                        skipTags: [\"body\"],\n                        processClass: \"bibbase_paper\"});\n  </script>\n\n  <style>\n  @media print {\n    .dontprint {\n        display: none !important;\n    }\n\n  .bibbase_group {\n    background-color: #E0E0E0;\n    font-style: italic;\n    font-size: larger;\n    text-shadow: 0px 0px 3px #FFFFFF;\n    border-radius: 4px 4px 4px 4px;\n    -moz-border-radius: 4px 4px 4px 4px;\n    -webkit-border-radius: 4px;\n    padding: 5px 40px 5px;\n    margin-top: 10px;\n    margin-bottom: 5px;\n    cursor: pointer;\n  }\n\n  .bibbase_paper {\n    margin-bottom: 5px;\n  }\n\n  }\n  </style>\n\n  \n  <div style=\"float: right; margin-right: 10px; margin-top: 10px; text-align: right; font-size: 12px\">\n    generated by\n    <a href=\"//bibbase.org\"\n       onclick=\"trackOutboundLink('bibbase', 'logo clicked', window.location.href, '//bibbase.org'); return false;\">\n      <img src=\"//bibbase.org/img/logo.svg\"\n           style=\"vertical-align: middle; margin-left: 3px; height: 16px;\"/\n           alt=\"bibbase.org\"\n           title=\"BibBase – The easiest way to maintain your publications page.\"\n        ></a>\n    \n  </div>\n  \n\n  <div id=\"bibbase_header\" class=\"dontprint\" style=\"\">\n\n    <ul class=\"nav nav-pills\" style=\"margin: 0px;\">\n\n      <li class=\"dropdown\" id=\"groupby_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\">\n          Group by\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li class=\"groupby year\"><a onclick=\"groupby('year')\">\n            Year</a>\n        </li>\n        <li class=\"groupby author\"><a onclick=\"groupby('author_short')\">\n            Author</a>\n        </li>\n        <li class=\"groupby type\"><a onclick=\"groupby('type')\">\n            Type</a>\n        </li>\n        <li class=\"groupby keyword\"><a onclick=\"groupby('keyword')\">\n            Keyword</a>\n        </li>\n        <li class=\"groupby downloads\"><a onclick=\"groupby('downloads')\">\n            Downloads</a>\n        </li>\n      </ul>\n      </li>\n\n\n      <li class=\"dropdown\" id=\"menu_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\" alt=\"controls\">\n          <i class=\"fa fa-reorder\" alt=\"controls\"></i>\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li>\n          <a onclick=\"toggleAll()\">\n            <i class=\"fa fa-chevron-down fa-fw\"></i> Expand/Collapse All\n          </a>\n        </li>\n        <li>\n          <a download=\"highlights.bib\" href=\"data:text/bibtex;base64,@article{RN41,
   author = {Jansen, J. F. and van Bussel, F. C. and van de Haar, H. J. and van Osch, M. J. and Hofman, P. A. and van Boxtel, M. P. and van Oostenbrugge, R. J. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Backes, W. H.},
   title = {Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus},
   journal = {Sci Rep},
   volume = {6},
   number = {1},
   pages = {10},
   ISSN = {2045-2322 (Electronic)
2045-2322 (Linking)},
   Abstract = {We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.},
   DOI = {10.1038/s41598-016-0003-6},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27920431},
   year = {2016},
   keywords = {a) Type 2 Diabetes Mellitus, h) Cerebrovascular MRI},
   type = {Journal Article}
}




@article{RN65,
   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and Puts, N. A. and Edden, R. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},
   title = {Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning},
   journal = {Medicine (Baltimore)},
   volume = {95},
   number = {36},
   pages = {e4803},
   ISSN = {1536-5964 (Electronic)
0025-7974 (Linking)},
   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.},
   DOI = {10.1097/MD.0000000000004803},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27603392},
   year = {2016},
   keywords = {cognition, functional MRI, magnetic resonance imaging, multiparametric MRI, type 2 diabetes mellitus},
   keywords = {a) Type 2 Diabetes Mellitus, e) Neurotransmitter MR Spectroscopy},
   type = {Journal Article}
}



@article{RN66,
   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},
   title = {Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements},
   journal = {J Neuroendocrinol},
   volume = {28},
   number = {3},
   pages = {12366},
   ISSN = {1365-2826 (Electronic)
0953-8194 (Linking)},
   Abstract = {Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.},
   DOI = {10.1111/jne.12366},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/26791354},
   year = {2016},
   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN67,
   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Oostenbrugge, R. J. and Kessels, A. G. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},
   title = {On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes},
   journal = {Diabetes Care},
   volume = {38},
   number = {5},
   pages = {876-82},
   ISSN = {1935-5548 (Electronic)
0149-5992 (Linking)},
   Abstract = {OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.},
   DOI = {10.2337/dc14-2043},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/25690006},
   year = {2015},
   keywords = {a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN68,
   author = {van Bussel, F. C. and Backes, W. H. and van Veenendaal, T. M. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Sep, S. J. and Dagnelie, P. C. and Schaper, N. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},
   title = {Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study},
   journal = {Diabetes},
   volume = {65},
   number = {8},
   pages = {2404-13},
   ISSN = {1939-327X (Electronic)
0012-1797 (Linking)},
   Abstract = {Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.},
   DOI = {10.2337/db16-0128},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27217484},
   year = {2016},
   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN70,
   author = {van Bussel, F. C. G. and Backes, W. H. and Hofman, P. A. M. and van Oostenbrugge, R. J. and van Boxtel, M. P. J. and Verhey, F. R. J. and Steinbusch, H. W. M. and Schram, M. T. and Stehouwer, C. D. A. and Wildberger, J. E. and Jansen, J. F. A.},
   title = {Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging},
   journal = {Front Neurosci},
   volume = {11},
   pages = {188},
   ISSN = {1662-4548 (Print)
1662-453X (Linking)},
   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.},
   DOI = {10.3389/fnins.2017.00188},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/28424581},
   year = {2017},
   keywords = {a) Type 2 Diabetes Mellitus},
   type = {Journal Article}
}



@article{RN83,
   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},
   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},
   journal = {Neuroimage Clin},
   volume = {19},
   pages = {47-55},
   ISSN = {2213-1582 (Electronic)
2213-1582 (Linking)},
   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.},
   DOI = {10.1016/j.nicl.2018.04.006},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},
   year = {2018},
   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN85,
   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Hofman, P. A. and Vlooswijk, M. C. and Rouhl, R. P. and de Louw, A. J. and Backes, W. H. and Jansen, J. F.},
   title = {Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review},
   journal = {Neurosci Biobehav Rev},
   volume = {59},
   pages = {92-9},
   ISSN = {1873-7528 (Electronic)
0149-7634 (Linking)},
   Abstract = {As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.},
   DOI = {10.1016/j.neubiorev.2015.10.004},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/26475992},
   year = {2015},
   keywords = {b) Epilepsy},
   type = {Journal Article}
}



@article{RN87,
   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Lazeron, R. H. C. and Puts, N. A. J. and Edden, R. A. E. and Hofman, P. A. M. and de Louw, A. J. A. and Backes, W. H. and Jansen, J. F. A.},
   title = {Glutamate concentrations vary with antiepileptic drug use and mental slowing},
   journal = {Epilepsy Behav},
   volume = {64},
   number = {Pt A},
   pages = {200-205},
   ISSN = {1525-5069 (Electronic)
1525-5050 (Linking)},
   Abstract = {OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.},
   DOI = {10.1016/j.yebeh.2016.08.027},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27744245},
   year = {2016},
   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy},
   type = {Journal Article}
}



@article{RN90,
   author = {Vlooswijk, M. C. and Jansen, J. F. and de Krom, M. C. and Majoie, H. M. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P.},
   title = {Functional MRI in chronic epilepsy: associations with cognitive impairment},
   journal = {Lancet Neurol},
   volume = {9},
   number = {10},
   pages = {1018-27},
   ISSN = {1474-4465 (Electronic)
1474-4422 (Linking)},
   Abstract = {Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.},
   DOI = {10.1016/S1474-4422(10)70180-0},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20708970},
   year = {2010},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN91,
   author = {Vlooswijk, M. C. and Jansen, J. F. and Jeukens, C. R. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},
   title = {Memory processes and prefrontal network dysfunction in cryptogenic epilepsy},
   journal = {Epilepsia},
   volume = {52},
   number = {8},
   pages = {1467-75},
   ISSN = {1528-1167 (Electronic)
0013-9580 (Linking)},
   Abstract = {PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.},
   DOI = {10.1111/j.1528-1167.2011.03108.x},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21635235},
   year = {2011},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN92,
   author = {Vlooswijk, M. C. and Jansen, J. F. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},
   title = {Functional connectivity and language impairment in cryptogenic localization-related epilepsy},
   journal = {Neurology},
   volume = {75},
   number = {5},
   pages = {395-402},
   ISSN = {1526-632X (Electronic)
0028-3878 (Linking)},
   Abstract = {BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.},
   DOI = {10.1212/WNL.0b013e3181ebdd3e},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20679633},
   year = {2010},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}


@article{RN94,
   author = {Vlooswijk, M. C. and Vaessen, M. J. and Jansen, J. F. and de Krom, M. C. and Majoie, H. J. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},
   title = {Loss of network efficiency associated with cognitive decline in chronic epilepsy},
   journal = {Neurology},
   volume = {77},
   number = {10},
   pages = {938-44},
   ISSN = {1526-632X (Electronic)
0028-3878 (Linking)},
   Abstract = {OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.},
   DOI = {10.1212/WNL.0b013e31822cfc2f},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/21832213},
   year = {2011},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN79,
   author = {van der Kruijs, S. J. and Bodde, N. M. and Vaessen, M. J. and Lazeron, R. H. and Vonck, K. and Boon, P. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F.},
   title = {Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures},
   journal = {J Neurol Neurosurg Psychiatry},
   volume = {83},
   number = {3},
   pages = {239-47},
   ISSN = {1468-330X (Electronic)
0022-3050 (Linking)},
   Abstract = {INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).},
   DOI = {10.1136/jnnp-2011-300776},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22056967},
   year = {2012},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN64,
   author = {Vaessen, M. J. and Jansen, J. F. and Vlooswijk, M. C. and Hofman, P. A. and Majoie, H. J. and Aldenkamp, A. P. and Backes, W. H.},
   title = {White matter network abnormalities are associated with cognitive decline in chronic epilepsy},
   journal = {Cereb Cortex},
   volume = {22},
   number = {9},
   pages = {2139-47},
   ISSN = {1460-2199 (Electronic)
1047-3211 (Linking)},
   Abstract = {Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.},
   DOI = {10.1093/cercor/bhr298},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22038907},
   year = {2012},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}




@article{RN61,
   author = {Vaessen, M. J. and Braakman, H. M. and Heerink, J. S. and Jansen, J. F. and Debeij-van Hall, M. H. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},
   title = {Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy},
   journal = {Cereb Cortex},
   volume = {23},
   number = {8},
   pages = {1997-2006},
   ISSN = {1460-2199 (Electronic)
1047-3211 (Linking)},
   Abstract = {Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.},
   DOI = {10.1093/cercor/bhs186},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22772649},
   year = {2013},
   keywords = {b) Epilepsy, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN71,
   author = {van de Haar, H. J. and Burgmans, S. and Hofman, P. A. and Verhey, F. R. and Jansen, J. F. and Backes, W. H.},
   title = {Blood-brain barrier impairment in dementia: current and future in vivo assessments},
   journal = {Neurosci Biobehav Rev},
   volume = {49},
   pages = {71-81},
   ISSN = {1873-7528 (Electronic)
0149-7634 (Linking)},
   Abstract = {Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.},
   DOI = {10.1016/j.neubiorev.2014.11.022},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/25524876},
   year = {2015},
   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN72,
   author = {van de Haar, H. J. and Burgmans, S. and Jansen, J. F. and van Osch, M. J. and van Buchem, M. A. and Muller, M. and Hofman, P. A. and Verhey, F. R. and Backes, W. H.},
   title = {Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease},
   journal = {Radiology},
   volume = {281},
   number = {2},
   pages = {527-535},
   ISSN = {1527-1315 (Electronic)
0033-8419 (Linking)},
   Abstract = {Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.},
   DOI = {10.1148/radiol.2016152244},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27243267},
   year = {2016},
   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}





@article{RN75,
   author = {van de Haar, H. J. and Jansen, J. F. A. and van Osch, M. J. P. and van Buchem, M. A. and Muller, M. and Wong, S. M. and Hofman, P. A. M. and Burgmans, S. and Verhey, F. R. J. and Backes, W. H.},
   title = {Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging},
   journal = {Neurobiol Aging},
   volume = {45},
   pages = {190-196},
   ISSN = {1558-1497 (Electronic)
0197-4580 (Linking)},
   Abstract = {The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.},
   DOI = {10.1016/j.neurobiolaging.2016.06.006},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27459939},
   year = {2016},
   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN3,
   author = {Backes, W. H. and Van Osch, M. J. and Van de Haar, H. J. and Jansen, J. F.},
   title = {Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response},
   journal = {Radiology},
   volume = {282},
   number = {3},
   pages = {924-25},
   ISSN = {1527-1315 (Electronic)
0033-8419 (Linking)},
   Abstract = {Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). 
Models employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility
(2). Therefore, we are happy to respond to these comments.},
   DOI = {10.1148/radiol.2017162578},
   url = {https://pubs.rsna.org/doi/10.1148/radiol.2017162578},
   year = {2017},
   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN95,
   author = {Wong, S. M. and Backes, W. H. and Zhang, C. E. and Staals, J. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Jansen, J. F. A.},
   title = {On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease},
   journal = {AJNR Am J Neuroradiol},
   volume = {39},
   number = {2},
   pages = {226-231},
   ISSN = {1936-959X (Electronic)
0195-6108 (Linking)},
   Abstract = {BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.},
   DOI = {10.3174/ajnr.A5474},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29217741},
   year = {2018},
   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN96,
   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Staals, J. and Hofman, P. A. M. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Backes, W. H.},
   title = {Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors},
   journal = {J Magn Reson Imaging},
   volume = {46},
   number = {1},
   pages = {159-166},
   ISSN = {1522-2586 (Electronic)
1053-1807 (Linking)},
   Abstract = {PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) </=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV </=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P < 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P < 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.},
   DOI = {10.1002/jmri.25540},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/28160347},
   year = {2017},
   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN97,
   author = {Wong, S. M. and Zhang, C. E. and van Bussel, F. C. and Staals, J. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H. and Jansen, J. F.},
   title = {Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging},
   journal = {Neuroimage Clin},
   volume = {14},
   pages = {216-221},
   ISSN = {2213-1582 (Electronic)
2213-1582 (Linking)},
   Abstract = {INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.},
   DOI = {10.1016/j.nicl.2017.01.017},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/28180080},
   year = {2017},
   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN98,
   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Backes, W. H. and Jansen, J. F. A. and Jeukens, Crlpn and van Oostenbrugge, R. J. and Staals, J.},
   title = {Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging},
   journal = {Brain Imaging Behav},
   ISSN = {1931-7565 (Electronic)
1931-7557 (Linking)},
   Abstract = {Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.},
   DOI = {10.1007/s11682-018-9855-7},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29572621},
   year = {2018},
   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN99,
   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Staals, J. and Backes, W. H. and Hoff, E. I. and Schreuder, T. and Jeukens, C. R. and Jansen, J. F. and van Oostenbrugge, R. J.},
   title = {Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition},
   journal = {Stroke},
   volume = {48},
   number = {3},
   pages = {658-663},
   ISSN = {1524-4628 (Electronic)
0039-2499 (Linking)},
   Abstract = {BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.},
   DOI = {10.1161/STROKEAHA.116.015084},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/28196940},
   year = {2017},
   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN100,
   author = {Zhang, C. E. and Wong, S. M. and van de Haar, H. J. and Staals, J. and Jansen, J. F. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H.},
   title = {Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease},
   journal = {Neurology},
   volume = {88},
   number = {5},
   pages = {426-432},
   ISSN = {1526-632X (Electronic)
0028-3878 (Linking)},
   Abstract = {OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.},
   DOI = {10.1212/WNL.0000000000003556},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/28031395},
   year = {2017},
   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}


@article{RN128,
   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},
   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},
   journal = {Neurology},
   volume = {92},
   number = {15},
   pages = {e1669-e1677},
   ISSN = {1526-632X (Electronic)
0028-3878 (Linking)},
   Abstract = {OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.},
   DOI = {10.1212/WNL.0000000000007263},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275},
   year = {2019},
   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN20,
   author = {Drenthen, G. S. and Barendse, E. M. and Aldenkamp, A. P. and van Veenendaal, T. M. and Puts, N. A. and Edden, R. A. and Zinger, S. and Thoonen, G. and Hendriks, M. P. and Kessels, R. P. and Jansen, J. F.},
   title = {Altered neurotransmitter metabolism in adolescents with high-functioning autism},
   journal = {Psychiatry Res Neuroimaging},
   volume = {256},
   pages = {44-49},
   ISSN = {1872-7506 (Electronic)
0925-4927 (Linking)},
   Abstract = {Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy ((1)H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few (1)H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using (1)H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.},
   DOI = {10.1016/j.pscychresns.2016.09.007},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/27685800},
   year = {2016},
   keywords = {e) Neurotransmitter MR Spectroscopy},
   type = {Journal Article}
}


@article{RN84,
   author = {van Veenendaal, T. M. and Backes, W. H. and van Bussel, F. C. G. and Edden, R. A. E. and Puts, N. A. J. and Aldenkamp, A. P. and Jansen, J. F. A.},
   title = {Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance},
   journal = {Magn Reson Imaging},
   volume = {48},
   pages = {107-114},
   ISSN = {1873-5894 (Electronic)
0730-725X (Linking)},
   Abstract = {PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.},
   DOI = {10.1016/j.mri.2017.12.029},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29306050},
   year = {2018},
   keywords = {e) Neurotransmitter MR Spectroscopy},
   type = {Journal Article}
}



@article{RN49,
   author = {Lu, Y. and Jansen, J. F. and Mazaheri, Y. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},
   title = {Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer},
   journal = {J Magn Reson Imaging},
   volume = {36},
   number = {5},
   pages = {1088-96},
   ISSN = {1522-2586 (Electronic)
1053-1807 (Linking)},
   Abstract = {PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.},
   DOI = {10.1002/jmri.23770},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22826198},
   year = {2012},
   keywords = {f) Advanced Diffusion Models},
   type = {Journal Article}
}



@article{RN40,
   author = {Jansen, J. F. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},
   title = {Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study},
   journal = {AJNR Am J Neuroradiol},
   volume = {31},
   number = {4},
   pages = {741-8},
   ISSN = {1936-959X (Electronic)
0195-6108 (Linking)},
   Abstract = {BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T. Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between K(app) and D(app). RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). D(app) was approximately twice the value of ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84). K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, K(app), potentially with added value.},
   DOI = {10.3174/ajnr.A1919},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/20037133},
   year = {2010},
   keywords = {f) Advanced Diffusion Models},
   type = {Journal Article}
}



@article{RN56,
   author = {Schnerr, R. S. and Jansen, J. F. A. and Uludag, K. and Hofman, P. A. M. and Wildberger, J. E. and van Oostenbrugge, R. J. and Backes, W. H.},
   title = {Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect},
   journal = {Front Physiol},
   volume = {8},
   pages = {961},
   ISSN = {1664-042X (Print)
1664-042X (Linking)},
   Abstract = {Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.},
   DOI = {10.3389/fphys.2017.00961},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29225580},
   year = {2017},
   keywords = {i) High Field MR, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN27,
   author = {Haast, R. A. M. and Ivanov, D. and RJT, I. Jsselstein and Sallevelt, Sceh and Jansen, J. F. A. and Smeets, H. J. M. and de Coo, I. F. M. and Formisano, E. and Uludag, K.},
   title = {Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study},
   journal = {Neuroimage Clin},
   volume = {18},
   pages = {231-244},
   ISSN = {2213-1582 (Electronic)
2213-1582 (Linking)},
   Abstract = {One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.},
   DOI = {10.1016/j.nicl.2018.01.017},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447},
   year = {2018},
   keywords = {i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging},
   type = {Journal Article}
}



@article{RN127,
   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F. A.},
   title = {Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration},
   journal = {Neuroimage},
   volume = {195},
   pages = {333-339},
   ISSN = {1095-9572 (Electronic)
1053-8119 (Linking)},
   Abstract = {Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30min still provides an excellent reproducibility.},
   Keywords = {Myelin water fraction
Reproducibility
T2 relaxometry},
   DOI = {10.1016/j.neuroimage.2019.04.011},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30965132},
   year = {2019},
   keywords = {j) Myelin Imaging},
   type = {Journal Article}
}



@article{RN121,
   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Op 't Veld, G. J. and Jansen, J. F. A.},
   title = {A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit},
   journal = {Magn Reson Med},
   volume = {81},
   number = {5},
   pages = {3292-3303},
   ISSN = {1522-2594 (Electronic)
0740-3194 (Linking)},
   Abstract = {PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.},
   Keywords = {T2 relaxometry
myelin water fraction
nonnegative least squares
orthogonal matching pursuit},
   DOI = {10.1002/mrm.27600},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30444019},
   year = {2019},
   keywords = {j) Myelin Imaging},
   type = {Journal Article}
}


@article{RN132,
   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Debeij - Van Hall, M. H. J. A. and Hendriksen, J. G. M. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},
   title = {Lower myelin-water content of the frontal lobe in childhood absence epilepsy},
   journal = {Epilepsia},
   volume = {0},
   number = {0},
   ISSN = {0013-9580},
   Abstract = {Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.},
   DOI = {10.1111/epi.16280},
   url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280},
   year = {2019},
   keywords = {b) Epilepsy, j) Myelin Imaging},
   type = {Journal Article}
}



@article{RN226,
   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},
   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},
   journal = {Neurology},
   volume = {92},
   number = {15},
   pages = {e1669-e1677},
   ISSN = {1526-632X (Electronic)
0028-3878 (Linking)},
   DOI = {10.1212/WNL.0000000000007263},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275
https://n.neurology.org/content/92/15/e1669.long},
   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},
   year = {2019},
   
   type = {Journal Article}
}



@article{RN234,
   author = {Wong, S. M. and Backes, W. H. and Drenthen, G. S. and Zhang, C. E. and Voorter, P. H. M. and Staals, J. and van Oostenbrugge, R. J. and Jansen, J. F. A.},
   title = {Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease},
   journal = {J Magn Reson Imaging},
   volume = {51},
   number = {4},
   pages = {1170-1180},
   ISSN = {1522-2586 (Electronic)
1053-1807 (Linking)},
   DOI = {10.1002/jmri.26920},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/31486211
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf},
   year = {2020},
   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},
   type = {Journal Article}
}



@article{RN247,
   author = {Vingerhoets, C. and Tse, D. H. Y. and Van Oudenaren, M. and Hernaus, D. and Van Duin, E. and Zinkstok, J. and Ramaekers, J. G. and Jansen, J. F. A. and McAlonan, G. and van Amelsvoort, T.},
   title = {Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.},
   journal = {J Psychopharmacol},
   DOI = {10.1177/0269881120922977},
   year = {2020},
   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},
   type = {Journal Article}
}



@article{RN233,
   author = {Vergoossen, L. W. and Schram, M. T. and de Jong, J. J. and Stehouwer, C. D. and Schaper, N. C. and Henry, R. M. and van der Kallen, C. J. and Dagnelie, P. C. and van Boxtel, M. P. and Eussen, S. J. and Backes, W. H. and Jansen, J. F.},
   title = {White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study},
   journal = {Diabetes Care},
   volume = {43},
   number = {1},
   pages = {201-208},
   ISSN = {1935-5548 (Electronic)
0149-5992 (Linking)},
   DOI = {10.2337/dc19-0762},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/31601638
https://care.diabetesjournals.org/content/43/1/201
https://care.diabetesjournals.org/content/43/1/201.long},
   year = {2020},
   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN213,
   author = {van Agtmaal, M. J. M. and Houben, Ajhm and de Wit, V. and Henry, R. M. A. and Schaper, N. C. and Dagnelie, P. C. and van der Kallen, C. J. and Koster, A. and Sep, S. J. and Kroon, A. A. and Jansen, J. F. A. and Hofman, P. A. and Backes, W. H. and Schram, M. T. and Stehouwer, C. D. A.},
   title = {Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study},
   journal = {Diabetes Care},
   volume = {41},
   number = {12},
   pages = {2535-2543},
   ISSN = {1935-5548 (Electronic)
0149-5992 (Linking)},
   DOI = {10.2337/dc18-1132},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/30327356
https://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf},
   year = {2018},
   keywords = {a) Type 2 Diabetes Mellitus},
   type = {Journal Article}
}



@article{RN224,
   author = {Mason, N. L. and Theunissen, E. L. and Hutten, Nrpw and Tse, D. H. Y. and Toennes, S. W. and Jansen, J. F. A. and Stiers, P. and Ramaekers, J. G.},
   title = {Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users},
   journal = {Addict Biol},
   pages = {e12870},
   ISSN = {1369-1600 (Electronic)
1355-6215 (Linking)},
   DOI = {10.1111/adb.12870},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/31865628
https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870},
   year = {2019},
   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},
   type = {Journal Article}
}



@inbook{RN240,
   author = {Jansen, J. F. and Wong, S. M. and Backes, W. H.},
   title = {IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease},
   booktitle = {Intravoxel Incoherent Motion (IVIM) MRI - Principles and Applications},
   editor = {Le Bihan, D. and Iima, M. and Federau, C. and Sigmund, E. E.},
   publisher = {Pan Stanford Publishing Pte. Ltd.},
   address = {Singapore},
   volume = {1},
   chapter = {4},
   pages = {85-98},
   ISBN = {9789814800198},
   DOI = {10.1201/9780429427275-4},
   url = {https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4},
   year = {2018},
   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},
   type = {Book Section}
}



@article{RN229,
   author = {Freeze, W. M. and Jacobs, H. I. L. and de Jong, J. J. and Verheggen, I. C. M. and Gronenschild, Ehbm and Palm, W. M. and Hoff, E. I. and Wardlaw, J. M. and Jansen, J. F. A. and Verhey, F. R. and Backes, W. H.},
   title = {White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed},
   journal = {Neurobiol Aging},
   volume = {85},
   pages = {113-122},
   ISSN = {1558-1497 (Electronic)
0197-4580 (Linking)},
   DOI = {10.1016/j.neurobiolaging.2019.09.017},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/31718926
https://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200414T144421Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0197458019303380&tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&type=client},
   year = {2020},
   keywords = {c) Alzheimer's Disease, h) Cerebrovascular MRI},
   type = {Journal Article}
}



@article{RN246,
   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Aldenkamp, A. P. and Vermeulen, R. J. and Debeij-van Hall, M. H. and Klinkenberg, S. and Jansen, J. F. A.},
   title = {Constructing an Axonal-Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy},
   journal = {J Neuroimaging},
   ISSN = {1552-6569 (Electronic)
1051-2284 (Linking)},
   DOI = {10.1111/jon.12707},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/32255537
https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707},
   year = {2020},
   keywords = {j) Myelin Imaging},
   type = {Journal Article}
}




@article{RN228,
   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},
   title = {On the merits of non-invasive myelin imaging in epilepsy, a literature review},
   journal = {J Neurosci Methods},
   pages = {108687},
   ISSN = {1872-678X (Electronic)
0165-0270 (Linking)},
   DOI = {10.1016/j.jneumeth.2020.108687},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/32173402
https://pdf.sciencedirectassets.com/271055/1-s2.0-S0165027020X00069/1-s2.0-S0165027020301096/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200414T144416Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=056b2124d0201d73cff3fdbc8782f9bf757551387d2965706f98fdbe39efd262&hash=4d7f86d5e3129e3315f7b93be2b4b0f22a8ce1e81eed96dd5fceeb7cf5fbaf78&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0165027020301096&tid=spdf-d2d2f778-426e-43b9-9ea8-f8dbd5cf3a81&sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&type=client},
   year = {2020},
   keywords = {j) Myelin Imaging},
   type = {Journal Article}
}


@article{RN257,
   author = {Canjels, L. P. W. and Backes, W. H. and van Veenendaal, T. M. and Vlooswijk, M. C. G. and Hofman, P. A. M. and Aldenkamp, A. P. and Rouhl, R. P. W. and Jansen, J. F. A.},
   title = {Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study},
   journal = {J Neuroimaging},
   ISSN = {1552-6569 (Electronic)
1051-2284 (Linking)},
   DOI = {10.1111/jon.12739},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/32472965
https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739},
   year = {2020},
   keywords = {b) Epilepsy, i) High Field MR},
   type = {Journal Article}
}



@article{RN253,
   author = {Mason, N. L. and Kuypers, K. P. C. and Muller, F. and Reckweg, J. and Tse, D. H. Y. and Toennes, S. W. and Hutten, Nrpw and Jansen, J. F. A. and Stiers, P. and Feilding, A. and Ramaekers, J. G.},
   title = {Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin},
   journal = {Neuropsychopharmacology},
   ISSN = {1740-634X (Electronic)
0893-133X (Linking)},
   DOI = {10.1038/s41386-020-0718-8},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/32446245
https://www.nature.com/articles/s41386-020-0718-8_reference.pdf},
   year = {2020},
   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},
   type = {Journal Article}
}



@article{RN307,
   author = {DeJong, N. R. and Jansen, J. F. A. and van Boxtel, M. P. J. and Schram, M. T. and Stehouwer, C. D. A. and Dagnelie, P. C. and van der Kallen, C. J. H. and Kroon, A. A. and Wesselius, A. and Koster, A. and Backes, W. H. and Kohler, S.},
   title = {Cognitive resilience depends on white matter connectivity: The Maastricht Study},
   journal = {Alzheimers Dement},
   ISSN = {1552-5279 (Electronic)
1552-5260 (Linking)},
   DOI = {10.1002/alz.12758},
   url = {https://www.ncbi.nlm.nih.gov/pubmed/35920350},
   year = {2022},
   keywords = {c) Alzheimer's Disease, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN305,
   author = {Drenthen, G. S. and Backes, W. H. and Freeze, W. M. and Jacobs, H. I. L. and Verheggen, I. C. M. and van Boxtel, M. P. J. and Hoff, E. I. and Verhey, F. R. and Jansen, J. F. A.},
   title = {Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease},
   journal = {J Alzheimers Dis},
   ISSN = {1875-8908 (Electronic)
1387-2877 (Linking)},
   DOI = {10.3233/JAD-220175},
   url = {https://www.ncbi.nlm.nih.gov/pubmed/35871335},
   year = {2022},
   keywords = {c) Alzheimer's Disease, g) Brain Connectivity},
   type = {Journal Article}
}



@article{RN280,
   author = {Monereo-Sanchez, J. and de Jong, J. J. A. and Drenthen, G. S. and Beran, M. and Backes, W. H. and Stehouwer, C. D. A. and Schram, M. T. and Linden, D. E. J. and Jansen, J. F. A.},
   title = {Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study},
   journal = {Neuroimage},
   pages = {118174},
   ISSN = {1095-9572 (Electronic)
1053-8119 (Linking)},
   DOI = {10.1016/j.neuroimage.2021.118174},
   url = {https://www.ncbi.nlm.nih.gov/pubmed/34000406},
   year = {2021},
   keywords = {k) MRI quality control},
   type = {Journal Article}
}
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In order to keep using Mendeley with BibBase past April\n        14th, you need to:\n        <ol>\n          <li>renew the authorization for BibBase on Mendeley, and</li>\n          <li>update the BibBase URL\n            in your page the same way you did when you initially set up\n            this page.\n          </li>\n        </ol>\n      </p>\n\n      <p>\n        <a href=\"http://bibbase.org/cgi-bin/mendeley2/get.py\">\n          <i class=\"fa fa-angle-double-right\"></i>\n          Fix it now</a>\n      </p>\n    </div>\n\n  </div>\n\n\n  <div id=\"bibbase_body\">\n    \n  \n  <div class=\"bibbase_group_whole\" id=\"group_a__Type_2_Diabetes_Mellitus\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_a__Type_2_Diabetes_Mellitus')\"\n      onkeypress=\"toggleGroup('group_a__Type_2_Diabetes_Mellitus')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>a) Type 2 Diabetes Mellitus</span>\n      <span class=\"bibbase_group_count\">\n        \n        (8)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27920431', event);\">\n    Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; van Bussel, F. C.; van de Haar, H. J.; van Osch, M. J.; Hofman, P. A.; van Boxtel, M. P.; van Oostenbrugge, R. J.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Sci Rep</i>, 6(1): 10.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\"\n     onclick=\"log_download('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27920431', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/s41598-016-0003-6\"\n     onclick=\"log_download('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://doi.org/10.1038/s41598-016-0003-6', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN41,\n   author = {Jansen, J. F. and van Bussel, F. C. and van de Haar, H. J. and van Osch, M. J. and Hofman, P. A. and van Boxtel, M. P. and van Oostenbrugge, R. J. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Backes, W. H.},\n   title = {Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus},\n   journal = {Sci Rep},\n   volume = {6},\n   number = {1},\n   pages = {10},\n   ISSN = {2045-2322 (Electronic)\n2045-2322 (Linking)},\n   Abstract = {We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a &#x27;distributed deviating voxels&#x27; method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total &#x27;distributed deviating voxels&#x27; demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.},\n   DOI = {10.1038/s41598-016-0003-6},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27920431},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27603392', event);\">\n    Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; Puts, N. A.; Edden, R. A.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Medicine (Baltimore)</i>, 95(36): e4803.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\"\n     onclick=\"log_download('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27603392', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1097/MD.0000000000004803\"\n     onclick=\"log_download('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://doi.org/10.1097/MD.0000000000004803', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN65,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and Puts, N. A. and Edden, R. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning},\n   journal = {Medicine (Baltimore)},\n   volume = {95},\n   number = {36},\n   pages = {e4803},\n   ISSN = {1536-5964 (Electronic)\n0025-7974 (Linking)},\n   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.},\n   DOI = {10.1097/MD.0000000000004803},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27603392},\n   year = {2016},\n   keywords = {cognition, functional MRI, magnetic resonance imaging, multiparametric MRI, type 2 diabetes mellitus},\n   keywords = {a) Type 2 Diabetes Mellitus, e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/26791354', event);\">\n    Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neuroendocrinol</i>, 28(3): 12366.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/26791354', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jne.12366\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://doi.org/10.1111/jne.12366', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN66,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements},\n   journal = {J Neuroendocrinol},\n   volume = {28},\n   number = {3},\n   pages = {12366},\n   ISSN = {1365-2826 (Electronic)\n0953-8194 (Linking)},\n   Abstract = {Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.},\n   DOI = {10.1111/jne.12366},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/26791354},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event);\">\n    On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; van Oostenbrugge, R. J.; Kessels, A. G.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 38(5): 876-82.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc14-2043\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://doi.org/10.2337/dc14-2043', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN67,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Oostenbrugge, R. J. and Kessels, A. G. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes},\n   journal = {Diabetes Care},\n   volume = {38},\n   number = {5},\n   pages = {876-82},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   Abstract = {OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.},\n   DOI = {10.2337/dc14-2043},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25690006},\n   year = {2015},\n   keywords = {a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27217484', event);\">\n    Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; van Veenendaal, T. M.; Hofman, P. A.; van Boxtel, M. P.; Schram, M. T.; Sep, S. J.; Dagnelie, P. C.; Schaper, N.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes</i>, 65(8): 2404-13.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\"\n     onclick=\"log_download('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27217484', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/db16-0128\"\n     onclick=\"log_download('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://doi.org/10.2337/db16-0128', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN68,\n   author = {van Bussel, F. C. and Backes, W. H. and van Veenendaal, T. M. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Sep, S. J. and Dagnelie, P. C. and Schaper, N. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study},\n   journal = {Diabetes},\n   volume = {65},\n   number = {8},\n   pages = {2404-13},\n   ISSN = {1939-327X (Electronic)\n0012-1797 (Linking)},\n   Abstract = {Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.},\n   DOI = {10.2337/db16-0128},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27217484},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28424581\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28424581', event);\">\n    Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C. G.; Backes, W. H.; Hofman, P. A. M.; van Oostenbrugge, R. J.; van Boxtel, M. P. J.; Verhey, F. R. J.; Steinbusch, H. W. M.; Schram, M. T.; Stehouwer, C. D. A.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Front Neurosci</i>, 11: 188.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28424581\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28424581', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3389/fnins.2017.00188\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017', 'http://doi.org/10.3389/fnins.2017.00188', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanoostenbrugge-vanboxtel-verhey-steinbusch-schram-etal-cerebralpathologyandcognitionindiabetesthemeritsofmultiparametricneuroimaging-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN70,\n   author = {van Bussel, F. C. G. and Backes, W. H. and Hofman, P. A. M. and van Oostenbrugge, R. J. and van Boxtel, M. P. J. and Verhey, F. R. J. and Steinbusch, H. W. M. and Schram, M. T. and Stehouwer, C. D. A. and Wildberger, J. E. and Jansen, J. F. A.},\n   title = {Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging},\n   journal = {Front Neurosci},\n   volume = {11},\n   pages = {188},\n   ISSN = {1662-4548 (Print)\n1662-453X (Linking)},\n   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.},\n   DOI = {10.3389/fnins.2017.00188},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28424581},\n   year = {2017},\n   keywords = {a) Type 2 Diabetes Mellitus},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long', event);\">\n    White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vergoossen, L. W.; Schram, M. T.; de Jong, J. J.; Stehouwer, C. D.; Schaper, N. C.; Henry, R. M.; van der Kallen, C. J.; Dagnelie, P. C.; van Boxtel, M. P.; Eussen, S. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 43(1): 201-208.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long\"\n     onclick=\"log_download('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc19-0762\"\n     onclick=\"log_download('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://doi.org/10.2337/dc19-0762', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN233,\n   author = {Vergoossen, L. W. and Schram, M. T. and de Jong, J. J. and Stehouwer, C. D. and Schaper, N. C. and Henry, R. M. and van der Kallen, C. J. and Dagnelie, P. C. and van Boxtel, M. P. and Eussen, S. J. and Backes, W. H. and Jansen, J. F.},\n   title = {White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study},\n   journal = {Diabetes Care},\n   volume = {43},\n   number = {1},\n   pages = {201-208},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   DOI = {10.2337/dc19-0762},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31601638\nhttps://care.diabetesjournals.org/content/43/1/201\nhttps://care.diabetesjournals.org/content/43/1/201.long},\n   year = {2020},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30327356 https://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30327356 https://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf', event);\">\n    Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Agtmaal, M. J. M.; Houben, A.; de Wit, V.; Henry, R. M. A.; Schaper, N. C.; Dagnelie, P. C.; van der Kallen, C. J.; Koster, A.; Sep, S. J.; Kroon, A. A.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Hofman, P. A.; Backes, W. H.; Schram, M. T.;  and Stehouwer, C. D. A.\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 41(12): 2535-2543.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30327356 https://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf\"\n     onclick=\"log_download('vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30327356 https://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc18-1132\"\n     onclick=\"log_download('vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018', 'http://doi.org/10.2337/dc18-1132', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanagtmaal-houben-dewit-henry-schaper-dagnelie-vanderkallen-koster-etal-prediabetesisassociatedwithstructuralbrainabnormalitiesthemaastrichtstudy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN213,\n   author = {van Agtmaal, M. J. M. and Houben, Ajhm and de Wit, V. and Henry, R. M. A. and Schaper, N. C. and Dagnelie, P. C. and van der Kallen, C. J. and Koster, A. and Sep, S. J. and Kroon, A. A. and Jansen, J. F. A. and Hofman, P. A. and Backes, W. H. and Schram, M. T. and Stehouwer, C. D. A.},\n   title = {Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study},\n   journal = {Diabetes Care},\n   volume = {41},\n   number = {12},\n   pages = {2535-2543},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   DOI = {10.2337/dc18-1132},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30327356\nhttps://care.diabetesjournals.org/content/diacare/41/12/2535.full.pdf},\n   year = {2018},\n   keywords = {a) Type 2 Diabetes Mellitus},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_b__Epilepsy\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_b__Epilepsy')\"\n      onkeypress=\"toggleGroup('group_b__Epilepsy')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>b) Epilepsy</span>\n      <span class=\"bibbase_group_count\">\n        \n        (12)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event);\">\n    High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; Backes, W. H.; Tse, D. H. Y.; Scheenen, T. W. J.; Klomp, D. W.; Hofman, P. A. M.; Rouhl, R. P. W.; Vlooswijk, M. C. G.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 19: 47-55.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.04.006\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://doi.org/10.1016/j.nicl.2018.04.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN83,\n   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},\n   journal = {Neuroimage Clin},\n   volume = {19},\n   pages = {47-55},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the &#x27;neurotransmitter networks&#x27; concept might also provide new insights for other neurological diseases.},\n   DOI = {10.1016/j.nicl.2018.04.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},\n   year = {2018},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26475992\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/26475992', event);\">\n    Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; DM, I. J.; Aldenkamp, A. P.; Hofman, P. A.; Vlooswijk, M. C.; Rouhl, R. P.; de Louw, A. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neurosci Biobehav Rev</i>, 59: 92-9.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26475992\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/26475992', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neubiorev.2015.10.004\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015', 'http://doi.org/10.1016/j.neubiorev.2015.10.004', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-dm-aldenkamp-hofman-vlooswijk-rouhl-delouw-backes-etal-metabolicandfunctionalmrbiomarkersofantiepilepticdrugeffectivenessareview-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN85,\n   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Hofman, P. A. and Vlooswijk, M. C. and Rouhl, R. P. and de Louw, A. J. and Backes, W. H. and Jansen, J. F.},\n   title = {Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review},\n   journal = {Neurosci Biobehav Rev},\n   volume = {59},\n   pages = {92-9},\n   ISSN = {1873-7528 (Electronic)\n0149-7634 (Linking)},\n   Abstract = {As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.},\n   DOI = {10.1016/j.neubiorev.2015.10.004},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/26475992},\n   year = {2015},\n   keywords = {b) Epilepsy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27744245', event);\">\n    Glutamate concentrations vary with antiepileptic drug use and mental slowing.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; DM, I. J.; Aldenkamp, A. P.; Lazeron, R. H. C.; Puts, N. A. J.; Edden, R. A. E.; Hofman, P. A. M.; de Louw, A. J. A.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsy Behav</i>, 64(Pt A): 200-205.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27744245', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Glutamate concentrations vary with antiepileptic drug use and mental slowing [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.yebeh.2016.08.027\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://doi.org/10.1016/j.yebeh.2016.08.027', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN87,\n   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Lazeron, R. H. C. and Puts, N. A. J. and Edden, R. A. E. and Hofman, P. A. M. and de Louw, A. J. A. and Backes, W. H. and Jansen, J. F. A.},\n   title = {Glutamate concentrations vary with antiepileptic drug use and mental slowing},\n   journal = {Epilepsy Behav},\n   volume = {64},\n   number = {Pt A},\n   pages = {200-205},\n   ISSN = {1525-5069 (Electronic)\n1525-5050 (Linking)},\n   Abstract = {OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.},\n   DOI = {10.1016/j.yebeh.2016.08.027},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27744245},\n   year = {2016},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20708970', event);\">\n    Functional MRI in chronic epilepsy: associations with cognitive impairment.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; de Krom, M. C.; Majoie, H. M.; Hofman, P. A.; Backes, W. H.;  and Aldenkamp, A. P.\n</span>\n\n  \n\n</span>\n\n  <i>Lancet Neurol</i>, 9(10): 1018-27.  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\"\n     onclick=\"log_download('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20708970', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional MRI in chronic epilepsy: associations with cognitive impairment [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/S1474-4422(10)70180-0\"\n     onclick=\"log_download('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://doi.org/10.1016/S1474-4422(10)70180-0', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN90,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and de Krom, M. C. and Majoie, H. M. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P.},\n   title = {Functional MRI in chronic epilepsy: associations with cognitive impairment},\n   journal = {Lancet Neurol},\n   volume = {9},\n   number = {10},\n   pages = {1018-27},\n   ISSN = {1474-4465 (Electronic)\n1474-4422 (Linking)},\n   Abstract = {Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.},\n   DOI = {10.1016/S1474-4422(10)70180-0},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20708970},\n   year = {2010},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21635235', event);\">\n    Memory processes and prefrontal network dysfunction in cryptogenic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Jeukens, C. R.; Majoie, H. J.; Hofman, P. A.; de Krom, M. C.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsia</i>, 52(8): 1467-75.  2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\"\n     onclick=\"log_download('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21635235', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Memory processes and prefrontal network dysfunction in cryptogenic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/j.1528-1167.2011.03108.x\"\n     onclick=\"log_download('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://doi.org/10.1111/j.1528-1167.2011.03108.x', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN91,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Jeukens, C. R. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Memory processes and prefrontal network dysfunction in cryptogenic epilepsy},\n   journal = {Epilepsia},\n   volume = {52},\n   number = {8},\n   pages = {1467-75},\n   ISSN = {1528-1167 (Electronic)\n0013-9580 (Linking)},\n   Abstract = {PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.},\n   DOI = {10.1111/j.1528-1167.2011.03108.x},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21635235},\n   year = {2011},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20679633', event);\">\n    Functional connectivity and language impairment in cryptogenic localization-related epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Majoie, H. J.; Hofman, P. A.; de Krom, M. C.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 75(5): 395-402.  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\"\n     onclick=\"log_download('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20679633', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional connectivity and language impairment in cryptogenic localization-related epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0b013e3181ebdd3e\"\n     onclick=\"log_download('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://doi.org/10.1212/WNL.0b013e3181ebdd3e', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN92,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Functional connectivity and language impairment in cryptogenic localization-related epilepsy},\n   journal = {Neurology},\n   volume = {75},\n   number = {5},\n   pages = {395-402},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.},\n   DOI = {10.1212/WNL.0b013e3181ebdd3e},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20679633},\n   year = {2010},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21832213', event);\">\n    Loss of network efficiency associated with cognitive decline in chronic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; Vaessen, M. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; de Krom, M. C.; Majoie, H. J.; Hofman, P. A.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 77(10): 938-44.  2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\"\n     onclick=\"log_download('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21832213', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Loss of network efficiency associated with cognitive decline in chronic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0b013e31822cfc2f\"\n     onclick=\"log_download('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://doi.org/10.1212/WNL.0b013e31822cfc2f', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN94,\n   author = {Vlooswijk, M. C. and Vaessen, M. J. and Jansen, J. F. and de Krom, M. C. and Majoie, H. J. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Loss of network efficiency associated with cognitive decline in chronic epilepsy},\n   journal = {Neurology},\n   volume = {77},\n   number = {10},\n   pages = {938-44},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.},\n   DOI = {10.1212/WNL.0b013e31822cfc2f},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21832213},\n   year = {2011},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22056967', event);\">\n    Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van der Kruijs, S. J.; Bodde, N. M.; Vaessen, M. J.; Lazeron, R. H.; Vonck, K.; Boon, P.; Hofman, P. A.; Backes, W. H.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neurol Neurosurg Psychiatry</i>, 83(3): 239-47.  2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\"\n     onclick=\"log_download('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22056967', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1136/jnnp-2011-300776\"\n     onclick=\"log_download('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://doi.org/10.1136/jnnp-2011-300776', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN79,\n   author = {van der Kruijs, S. J. and Bodde, N. M. and Vaessen, M. J. and Lazeron, R. H. and Vonck, K. and Boon, P. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F.},\n   title = {Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures},\n   journal = {J Neurol Neurosurg Psychiatry},\n   volume = {83},\n   number = {3},\n   pages = {239-47},\n   ISSN = {1468-330X (Electronic)\n0022-3050 (Linking)},\n   Abstract = {INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven&#x27;s Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).},\n   DOI = {10.1136/jnnp-2011-300776},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22056967},\n   year = {2012},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22038907', event);\">\n    White matter network abnormalities are associated with cognitive decline in chronic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vaessen, M. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Vlooswijk, M. C.; Hofman, P. A.; Majoie, H. J.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Cereb Cortex</i>, 22(9): 2139-47.  2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\"\n     onclick=\"log_download('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22038907', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White matter network abnormalities are associated with cognitive decline in chronic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/cercor/bhr298\"\n     onclick=\"log_download('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://doi.org/10.1093/cercor/bhr298', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN64,\n   author = {Vaessen, M. J. and Jansen, J. F. and Vlooswijk, M. C. and Hofman, P. A. and Majoie, H. J. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {White matter network abnormalities are associated with cognitive decline in chronic epilepsy},\n   journal = {Cereb Cortex},\n   volume = {22},\n   number = {9},\n   pages = {2139-47},\n   ISSN = {1460-2199 (Electronic)\n1047-3211 (Linking)},\n   Abstract = {Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.},\n   DOI = {10.1093/cercor/bhr298},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22038907},\n   year = {2012},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://www.ncbi.nlm.nih.gov/pubmed/22772649', event);\">\n    Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vaessen, M. J.; Braakman, H. M.; Heerink, J. S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Debeij-van Hall, M. H.; Hofman, P. A.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Cereb Cortex</i>, 23(8): 1997-2006.  2013.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\"\n     onclick=\"log_download('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://www.ncbi.nlm.nih.gov/pubmed/22772649', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/cercor/bhs186\"\n     onclick=\"log_download('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://doi.org/10.1093/cercor/bhs186', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN61,\n   author = {Vaessen, M. J. and Braakman, H. M. and Heerink, J. S. and Jansen, J. F. and Debeij-van Hall, M. H. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy},\n   journal = {Cereb Cortex},\n   volume = {23},\n   number = {8},\n   pages = {1997-2006},\n   ISSN = {1460-2199 (Electronic)\n1047-3211 (Linking)},\n   Abstract = {Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.},\n   DOI = {10.1093/cercor/bhs186},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22772649},\n   year = {2013},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280', event);\">\n    Lower myelin-water content of the frontal lobe in childhood absence epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Fonseca Wald, E. L. A.; Backes, W. H.; Debeij - Van Hall, M. H. J. A.; Hendriksen, J. G. M.; Aldenkamp, A. P.; Vermeulen, R. J.; Klinkenberg, S.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsia</i>, 0(0).  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Lower myelin-water content of the frontal lobe in childhood absence epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/epi.16280\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'http://doi.org/10.1111/epi.16280', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN132,\n   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Debeij - Van Hall, M. H. J. A. and Hendriksen, J. G. M. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},\n   title = {Lower myelin-water content of the frontal lobe in childhood absence epilepsy},\n   journal = {Epilepsia},\n   volume = {0},\n   number = {0},\n   ISSN = {0013-9580},\n   Abstract = {Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P &gt; 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.},\n   DOI = {10.1111/epi.16280},\n   url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280},\n   year = {2019},\n   keywords = {b) Epilepsy, j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739', event);\">\n    Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Canjels, L. P. W.; Backes, W. H.; van Veenendaal, T. M.; Vlooswijk, M. C. G.; Hofman, P. A. M.; Aldenkamp, A. P.; Rouhl, R. P. W.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neuroimaging</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739\"\n     onclick=\"log_download('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jon.12739\"\n     onclick=\"log_download('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://doi.org/10.1111/jon.12739', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>3 downloads</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN257,\n   author = {Canjels, L. P. W. and Backes, W. H. and van Veenendaal, T. M. and Vlooswijk, M. C. G. and Hofman, P. A. M. and Aldenkamp, A. P. and Rouhl, R. P. W. and Jansen, J. F. A.},\n   title = {Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study},\n   journal = {J Neuroimaging},\n   ISSN = {1552-6569 (Electronic)\n1051-2284 (Linking)},\n   DOI = {10.1111/jon.12739},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32472965\nhttps://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739},\n   year = {2020},\n   keywords = {b) Epilepsy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_c__Alzheimer_s_Disease\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_c__Alzheimer_s_Disease')\"\n      onkeypress=\"toggleGroup('group_c__Alzheimer_s_Disease')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>c) Alzheimer&#x27;s Disease</span>\n      <span class=\"bibbase_group_count\">\n        \n        (7)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25524876', event);\">\n    Blood-brain barrier impairment in dementia: current and future in vivo assessments.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; Burgmans, S.; Hofman, P. A.; Verhey, F. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurosci Biobehav Rev</i>, 49: 71-81.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\"\n     onclick=\"log_download('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25524876', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment in dementia: current and future in vivo assessments [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neubiorev.2014.11.022\"\n     onclick=\"log_download('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://doi.org/10.1016/j.neubiorev.2014.11.022', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN71,\n   author = {van de Haar, H. J. and Burgmans, S. and Hofman, P. A. and Verhey, F. R. and Jansen, J. F. and Backes, W. H.},\n   title = {Blood-brain barrier impairment in dementia: current and future in vivo assessments},\n   journal = {Neurosci Biobehav Rev},\n   volume = {49},\n   pages = {71-81},\n   ISSN = {1873-7528 (Electronic)\n0149-7634 (Linking)},\n   Abstract = {Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.},\n   DOI = {10.1016/j.neubiorev.2014.11.022},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25524876},\n   year = {2015},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27243267', event);\">\n    Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; Burgmans, S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; van Osch, M. J.; van Buchem, M. A.; Muller, M.; Hofman, P. A.; Verhey, F. R.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Radiology</i>, 281(2): 527-535.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\"\n     onclick=\"log_download('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27243267', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1148/radiol.2016152244\"\n     onclick=\"log_download('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://doi.org/10.1148/radiol.2016152244', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN72,\n   author = {van de Haar, H. J. and Burgmans, S. and Jansen, J. F. and van Osch, M. J. and van Buchem, M. A. and Muller, M. and Hofman, P. A. and Verhey, F. R. and Backes, W. H.},\n   title = {Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease},\n   journal = {Radiology},\n   volume = {281},\n   number = {2},\n   pages = {527-535},\n   ISSN = {1527-1315 (Electronic)\n0033-8419 (Linking)},\n   Abstract = {Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P &lt; .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P &lt; .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P &lt; .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.},\n   DOI = {10.1148/radiol.2016152244},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27243267},\n   year = {2016},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27459939', event);\">\n    Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; van Osch, M. J. P.; van Buchem, M. A.; Muller, M.; Wong, S. M.; Hofman, P. A. M.; Burgmans, S.; Verhey, F. R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurobiol Aging</i>, 45: 190-196.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\"\n     onclick=\"log_download('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27459939', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Neurovascular unit impairment in early Alzheimer&#x27;s disease measured with magnetic resonance imaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neurobiolaging.2016.06.006\"\n     onclick=\"log_download('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://doi.org/10.1016/j.neurobiolaging.2016.06.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN75,\n   author = {van de Haar, H. J. and Jansen, J. F. A. and van Osch, M. J. P. and van Buchem, M. A. and Muller, M. and Wong, S. M. and Hofman, P. A. M. and Burgmans, S. and Verhey, F. R. J. and Backes, W. H.},\n   title = {Neurovascular unit impairment in early Alzheimer&#x27;s disease measured with magnetic resonance imaging},\n   journal = {Neurobiol Aging},\n   volume = {45},\n   pages = {190-196},\n   ISSN = {1558-1497 (Electronic)\n0197-4580 (Linking)},\n   Abstract = {The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer&#x27;s Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.},\n   DOI = {10.1016/j.neurobiolaging.2016.06.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27459939},\n   year = {2016},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'https://pubs.rsna.org/doi/10.1148/radiol.2017162578', event);\">\n    Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Backes, W. H.; Van Osch, M. J.; Van de Haar, H. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Radiology</i>, 282(3): 924-25.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\"\n     onclick=\"log_download('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'https://pubs.rsna.org/doi/10.1148/radiol.2017162578', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1148/radiol.2017162578\"\n     onclick=\"log_download('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'http://doi.org/10.1148/radiol.2017162578', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN3,\n   author = {Backes, W. H. and Van Osch, M. J. and Van de Haar, H. J. and Jansen, J. F.},\n   title = {Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response},\n   journal = {Radiology},\n   volume = {282},\n   number = {3},\n   pages = {924-25},\n   ISSN = {1527-1315 (Electronic)\n0033-8419 (Linking)},\n   Abstract = {Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). \nModels employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility\n(2). Therefore, we are happy to respond to these comments.},\n   DOI = {10.1148/radiol.2017162578},\n   url = {https://pubs.rsna.org/doi/10.1148/radiol.2017162578},\n   year = {2017},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). Models employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility (2). Therefore, we are happy to respond to these comments.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31718926 https://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144421Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&amp;hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0197458019303380&amp;tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31718926 https://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144421Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&amp;hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0197458019303380&amp;tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client', event);\">\n    White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Freeze, W. M.; Jacobs, H. I. L.; de Jong, J. J.; Verheggen, I. C. M.; Gronenschild, E.; Palm, W. M.; Hoff, E. I.; Wardlaw, J. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Verhey, F. R.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurobiol Aging</i>, 85: 113-122.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31718926 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event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neurobiolaging.2019.09.017\"\n     onclick=\"log_download('freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020', 'http://doi.org/10.1016/j.neurobiolaging.2019.09.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN229,\n   author = {Freeze, W. M. and Jacobs, H. I. L. and de Jong, J. J. and Verheggen, I. C. M. and Gronenschild, Ehbm and Palm, W. M. and Hoff, E. I. and Wardlaw, J. M. and Jansen, J. F. A. and Verhey, F. R. and Backes, W. H.},\n   title = {White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed},\n   journal = {Neurobiol Aging},\n   volume = {85},\n   pages = {113-122},\n   ISSN = {1558-1497 (Electronic)\n0197-4580 (Linking)},\n   DOI = {10.1016/j.neurobiolaging.2019.09.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31718926\nhttps://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144421Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&amp;hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0197458019303380&amp;tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client},\n   year = {2020},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35920350', event);\">\n    Cognitive resilience depends on white matter connectivity: The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  DeJong, N. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; van Boxtel, M. P. J.; Schram, M. T.; Stehouwer, C. D. A.; Dagnelie, P. C.; van der Kallen, C. J. H.; Kroon, A. A.; Wesselius, A.; Koster, A.; Backes, W. H.;  and Kohler, S.\n</span>\n\n  \n\n</span>\n\n  <i>Alzheimers Dement</i>.  2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\"\n     onclick=\"log_download('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35920350', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Cognitive resilience depends on white matter connectivity: The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/alz.12758\"\n     onclick=\"log_download('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'http://doi.org/10.1002/alz.12758', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN307,\n   author = {DeJong, N. R. and Jansen, J. F. A. and van Boxtel, M. P. J. and Schram, M. T. and Stehouwer, C. D. A. and Dagnelie, P. C. and van der Kallen, C. J. H. and Kroon, A. A. and Wesselius, A. and Koster, A. and Backes, W. H. and Kohler, S.},\n   title = {Cognitive resilience depends on white matter connectivity: The Maastricht Study},\n   journal = {Alzheimers Dement},\n   ISSN = {1552-5279 (Electronic)\n1552-5260 (Linking)},\n   DOI = {10.1002/alz.12758},\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35920350},\n   year = {2022},\n   keywords = {c) Alzheimer&#x27;s Disease, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35871335', event);\">\n    Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Backes, W. H.; Freeze, W. M.; Jacobs, H. I. L.; Verheggen, I. C. M.; van Boxtel, M. P. J.; Hoff, E. I.; Verhey, F. R.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Alzheimers Dis</i>.  2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\"\n     onclick=\"log_download('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35871335', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer&#x27;s Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3233/JAD-220175\"\n     onclick=\"log_download('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'http://doi.org/10.3233/JAD-220175', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN305,\n   author = {Drenthen, G. S. and Backes, W. H. and Freeze, W. M. and Jacobs, H. I. L. and Verheggen, I. C. M. and van Boxtel, M. P. J. and Hoff, E. I. and Verhey, F. R. and Jansen, J. F. A.},\n   title = {Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer&#x27;s Disease},\n   journal = {J Alzheimers Dis},\n   ISSN = {1875-8908 (Electronic)\n1387-2877 (Linking)},\n   DOI = {10.3233/JAD-220175},\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35871335},\n   year = {2022},\n   keywords = {c) Alzheimer&#x27;s Disease, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_d__Cerebral_Small_Vessel_Disease\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_d__Cerebral_Small_Vessel_Disease')\"\n      onkeypress=\"toggleGroup('group_d__Cerebral_Small_Vessel_Disease')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>d) Cerebral Small Vessel Disease</span>\n      <span class=\"bibbase_group_count\">\n        \n        (10)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event);\">\n    On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Backes, W. H.; Zhang, C. E.; Staals, J.; van Oostenbrugge, R. J.; Jeukens, C.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>AJNR Am J Neuroradiol</i>, 39(2): 226-231.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3174/ajnr.A5474\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://doi.org/10.3174/ajnr.A5474', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN95,\n   author = {Wong, S. M. and Backes, W. H. and Zhang, C. E. and Staals, J. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Jansen, J. F. A.},\n   title = {On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease},\n   journal = {AJNR Am J Neuroradiol},\n   volume = {39},\n   number = {2},\n   pages = {226-231},\n   ISSN = {1936-959X (Electronic)\n0195-6108 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were &lt;3.70% in normal-appearing tissue and &lt;9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.},\n   DOI = {10.3174/ajnr.A5474},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29217741},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28160347', event);\">\n    Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Staals, J.; Hofman, P. A. M.; van Oostenbrugge, R. J.; Jeukens, C.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>J Magn Reson Imaging</i>, 46(1): 159-166.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\"\n     onclick=\"log_download('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28160347', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jmri.25540\"\n     onclick=\"log_download('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://doi.org/10.1002/jmri.25540', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN96,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Staals, J. and Hofman, P. A. M. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Backes, W. H.},\n   title = {Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors},\n   journal = {J Magn Reson Imaging},\n   volume = {46},\n   number = {1},\n   pages = {159-166},\n   ISSN = {1522-2586 (Electronic)\n1053-1807 (Linking)},\n   Abstract = {PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) &lt;/=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV &lt;/=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P &lt; 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P &lt; 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.},\n   DOI = {10.1002/jmri.25540},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28160347},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) </=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV </=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P < 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P < 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event);\">\n    Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Zhang, C. E.; van Bussel, F. C.; Staals, J.; Jeukens, C. R.; Hofman, P. A.; van Oostenbrugge, R. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 14: 216-221.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2017.01.017\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://doi.org/10.1016/j.nicl.2017.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN97,\n   author = {Wong, S. M. and Zhang, C. E. and van Bussel, F. C. and Staals, J. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H. and Jansen, J. F.},\n   title = {Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging},\n   journal = {Neuroimage Clin},\n   volume = {14},\n   pages = {216-221},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p &lt; 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p &lt; 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p &lt; 0.024) and D (p &lt; 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.},\n   DOI = {10.1016/j.nicl.2017.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28180080},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29572621', event);\">\n    Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; Uiterwijk, R.; Backes, W. H.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Jeukens, C.; van Oostenbrugge, R. J.;  and Staals, J.\n</span>\n\n  \n\n</span>\n\n  <i>Brain Imaging Behav</i>.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\"\n     onclick=\"log_download('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29572621', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s11682-018-9855-7\"\n     onclick=\"log_download('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://doi.org/10.1007/s11682-018-9855-7', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN98,\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Backes, W. H. and Jansen, J. F. A. and Jeukens, Crlpn and van Oostenbrugge, R. J. and Staals, J.},\n   title = {Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging},\n   journal = {Brain Imaging Behav},\n   ISSN = {1931-7565 (Electronic)\n1931-7557 (Linking)},\n   Abstract = {Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.},\n   DOI = {10.1007/s11682-018-9855-7},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29572621},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event);\">\n    Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; Uiterwijk, R.; Staals, J.; Backes, W. H.; Hoff, E. I.; Schreuder, T.; Jeukens, C. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>;  and van Oostenbrugge, R. J.\n</span>\n\n  \n\n</span>\n\n  <i>Stroke</i>, 48(3): 658-663.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1161/STROKEAHA.116.015084\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://doi.org/10.1161/STROKEAHA.116.015084', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN99,\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Staals, J. and Backes, W. H. and Hoff, E. I. and Schreuder, T. and Jeukens, C. R. and Jansen, J. F. and van Oostenbrugge, R. J.},\n   title = {Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition},\n   journal = {Stroke},\n   volume = {48},\n   number = {3},\n   pages = {658-663},\n   ISSN = {1524-4628 (Electronic)\n0039-2499 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.},\n   DOI = {10.1161/STROKEAHA.116.015084},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28196940},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28031395', event);\">\n    Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; van de Haar, H. J.; Staals, J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Jeukens, C. R.; Hofman, P. A.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 88(5): 426-432.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\"\n     onclick=\"log_download('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28031395', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000003556\"\n     onclick=\"log_download('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://doi.org/10.1212/WNL.0000000000003556', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN100,\n   author = {Zhang, C. E. and Wong, S. M. and van de Haar, H. J. and Staals, J. and Jansen, J. F. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {88},\n   number = {5},\n   pages = {426-432},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.},\n   DOI = {10.1212/WNL.0000000000003556},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28031395},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275', event);\">\n    Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Hoff, E. I.; Staals, J.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 92(15): e1669-e1677.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000007263\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://doi.org/10.1212/WNL.0000000000007263', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN128,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {92},\n   number = {15},\n   pages = {e1669-e1677},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p &lt; 0.01) and an increase in leakage volume of 0.7% (p &lt; 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 &lt; r &lt; -0.40, p &lt; 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.},\n   DOI = {10.1212/WNL.0000000000007263},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275},\n   year = {2019},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long', event);\">\n    Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Hoff, E. I.; Staals, J.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 92(15): e1669-e1677.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000007263\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://doi.org/10.1212/WNL.0000000000007263', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN226,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {92},\n   number = {15},\n   pages = {e1669-e1677},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   DOI = {10.1212/WNL.0000000000007263},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275\nhttps://n.neurology.org/content/92/15/e1669.long},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   year = {2019},\n   \n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf', event);\">\n    Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Backes, W. H.; Drenthen, G. S.; Zhang, C. E.; Voorter, P. H. M.; Staals, J.; van Oostenbrugge, R. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Magn Reson Imaging</i>, 51(4): 1170-1180.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\"\n     onclick=\"log_download('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jmri.26920\"\n     onclick=\"log_download('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://doi.org/10.1002/jmri.26920', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN234,\n   author = {Wong, S. M. and Backes, W. H. and Drenthen, G. S. and Zhang, C. E. and Voorter, P. H. M. and Staals, J. and van Oostenbrugge, R. J. and Jansen, J. F. A.},\n   title = {Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease},\n   journal = {J Magn Reson Imaging},\n   volume = {51},\n   number = {4},\n   pages = {1170-1180},\n   ISSN = {1522-2586 (Electronic)\n1053-1807 (Linking)},\n   DOI = {10.1002/jmri.26920},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31486211\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf},\n   year = {2020},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4', event);\">\n    IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Wong, S. M.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  Volume 1 . IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease, pages 85-98. Le Bihan, D.; Iima, M.; Federau, C.;  and Sigmund, E. E., editor(s). Pan Stanford Publishing Pte. Ltd., Singapore,  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4\"\n     onclick=\"log_download('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1201/9780429427275-4\"\n     onclick=\"log_download('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'http://doi.org/10.1201/9780429427275-4', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>3 downloads</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@inbook{RN240,\n   author = {Jansen, J. F. and Wong, S. M. and Backes, W. H.},\n   title = {IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease},\n   booktitle = {Intravoxel Incoherent Motion (IVIM) MRI - Principles and Applications},\n   editor = {Le Bihan, D. and Iima, M. and Federau, C. and Sigmund, E. E.},\n   publisher = {Pan Stanford Publishing Pte. Ltd.},\n   address = {Singapore},\n   volume = {1},\n   chapter = {4},\n   pages = {85-98},\n   ISBN = {9789814800198},\n   DOI = {10.1201/9780429427275-4},\n   url = {https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},\n   type = {Book Section}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_e__Neurotransmitter_MR_Spectroscopy\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_e__Neurotransmitter_MR_Spectroscopy')\"\n      onkeypress=\"toggleGroup('group_e__Neurotransmitter_MR_Spectroscopy')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>e) Neurotransmitter MR Spectroscopy</span>\n      <span class=\"bibbase_group_count\">\n        \n        (8)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27603392', event);\">\n    Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; Puts, N. A.; Edden, R. A.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Medicine (Baltimore)</i>, 95(36): e4803.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27603392\"\n     onclick=\"log_download('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27603392', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1097/MD.0000000000004803\"\n     onclick=\"log_download('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016', 'http://doi.org/10.1097/MD.0000000000004803', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-puts-edden-vanboxtel-schram-stehouwer-etal-increasedgabaconcentrationsintype2diabetesmellitusarerelatedtolowercognitivefunctioning-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN65,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and Puts, N. A. and Edden, R. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning},\n   journal = {Medicine (Baltimore)},\n   volume = {95},\n   number = {36},\n   pages = {e4803},\n   ISSN = {1536-5964 (Electronic)\n0025-7974 (Linking)},\n   Abstract = {Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.},\n   DOI = {10.1097/MD.0000000000004803},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27603392},\n   year = {2016},\n   keywords = {cognition, functional MRI, magnetic resonance imaging, multiparametric MRI, type 2 diabetes mellitus},\n   keywords = {a) Type 2 Diabetes Mellitus, e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event);\">\n    High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; Backes, W. H.; Tse, D. H. Y.; Scheenen, T. W. J.; Klomp, D. W.; Hofman, P. A. M.; Rouhl, R. P. W.; Vlooswijk, M. C. G.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 19: 47-55.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.04.006\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://doi.org/10.1016/j.nicl.2018.04.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN83,\n   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},\n   journal = {Neuroimage Clin},\n   volume = {19},\n   pages = {47-55},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the &#x27;neurotransmitter networks&#x27; concept might also provide new insights for other neurological diseases.},\n   DOI = {10.1016/j.nicl.2018.04.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},\n   year = {2018},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27744245', event);\">\n    Glutamate concentrations vary with antiepileptic drug use and mental slowing.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; DM, I. J.; Aldenkamp, A. P.; Lazeron, R. H. C.; Puts, N. A. J.; Edden, R. A. E.; Hofman, P. A. M.; de Louw, A. J. A.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsy Behav</i>, 64(Pt A): 200-205.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27744245\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27744245', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Glutamate concentrations vary with antiepileptic drug use and mental slowing [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.yebeh.2016.08.027\"\n     onclick=\"log_download('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016', 'http://doi.org/10.1016/j.yebeh.2016.08.027', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-dm-aldenkamp-lazeron-puts-edden-hofman-delouw-etal-glutamateconcentrationsvarywithantiepilepticdruguseandmentalslowing-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN87,\n   author = {van Veenendaal, T. M. and DM, I. Jff and Aldenkamp, A. P. and Lazeron, R. H. C. and Puts, N. A. J. and Edden, R. A. E. and Hofman, P. A. M. and de Louw, A. J. A. and Backes, W. H. and Jansen, J. F. A.},\n   title = {Glutamate concentrations vary with antiepileptic drug use and mental slowing},\n   journal = {Epilepsy Behav},\n   volume = {64},\n   number = {Pt A},\n   pages = {200-205},\n   ISSN = {1525-5069 (Electronic)\n1525-5050 (Linking)},\n   Abstract = {OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.},\n   DOI = {10.1016/j.yebeh.2016.08.027},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27744245},\n   year = {2016},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27685800\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27685800', event);\">\n    Altered neurotransmitter metabolism in adolescents with high-functioning autism.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Barendse, E. M.; Aldenkamp, A. P.; van Veenendaal, T. M.; Puts, N. A.; Edden, R. A.; Zinger, S.; Thoonen, G.; Hendriks, M. P.; Kessels, R. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Psychiatry Res Neuroimaging</i>, 256: 44-49.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27685800\"\n     onclick=\"log_download('drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27685800', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Altered neurotransmitter metabolism in adolescents with high-functioning autism [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.pscychresns.2016.09.007\"\n     onclick=\"log_download('drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016', 'http://doi.org/10.1016/j.pscychresns.2016.09.007', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-barendse-aldenkamp-vanveenendaal-puts-edden-zinger-thoonen-etal-alteredneurotransmittermetabolisminadolescentswithhighfunctioningautism-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN20,\n   author = {Drenthen, G. S. and Barendse, E. M. and Aldenkamp, A. P. and van Veenendaal, T. M. and Puts, N. A. and Edden, R. A. and Zinger, S. and Thoonen, G. and Hendriks, M. P. and Kessels, R. P. and Jansen, J. F.},\n   title = {Altered neurotransmitter metabolism in adolescents with high-functioning autism},\n   journal = {Psychiatry Res Neuroimaging},\n   volume = {256},\n   pages = {44-49},\n   ISSN = {1872-7506 (Electronic)\n0925-4927 (Linking)},\n   Abstract = {Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy ((1)H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few (1)H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using (1)H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.},\n   DOI = {10.1016/j.pscychresns.2016.09.007},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27685800},\n   year = {2016},\n   keywords = {e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy ((1)H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few (1)H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using (1)H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29306050\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29306050', event);\">\n    Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; Backes, W. H.; van Bussel, F. C. G.; Edden, R. A. E.; Puts, N. A. J.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Magn Reson Imaging</i>, 48: 107-114.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29306050\"\n     onclick=\"log_download('vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29306050', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.mri.2017.12.029\"\n     onclick=\"log_download('vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018', 'http://doi.org/10.1016/j.mri.2017.12.029', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-backes-vanbussel-edden-puts-aldenkamp-jansen-glutamatequantificationbypressormegapressvalidationrepeatabilityandconcordance-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN84,\n   author = {van Veenendaal, T. M. and Backes, W. H. and van Bussel, F. C. G. and Edden, R. A. E. and Puts, N. A. J. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance},\n   journal = {Magn Reson Imaging},\n   volume = {48},\n   pages = {107-114},\n   ISSN = {1873-5894 (Electronic)\n0730-725X (Linking)},\n   Abstract = {PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r&gt;0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.},\n   DOI = {10.1016/j.mri.2017.12.029},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29306050},\n   year = {2018},\n   keywords = {e) Neurotransmitter MR Spectroscopy},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vingerhoets, C.; Tse, D. H. Y.; Van Oudenaren, M.; Hernaus, D.; Van Duin, E.; Zinkstok, J.; Ramaekers, J. G.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; McAlonan, G.;  and van Amelsvoort, T.\n</span>\n\n  \n\n</span>\n\n  <i>J Psychopharmacol</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1177/0269881120922977\"\n     onclick=\"log_download('vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020', 'http://doi.org/10.1177/0269881120922977', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN247,\n   author = {Vingerhoets, C. and Tse, D. H. Y. and Van Oudenaren, M. and Hernaus, D. and Van Duin, E. and Zinkstok, J. and Ramaekers, J. G. and Jansen, J. F. A. and McAlonan, G. and van Amelsvoort, T.},\n   title = {Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.},\n   journal = {J Psychopharmacol},\n   DOI = {10.1177/0269881120922977},\n   year = {2020},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870', event);\">\n    Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Mason, N. L.; Theunissen, E. L.; Hutten, N.; Tse, D. H. Y.; Toennes, S. W.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Stiers, P.;  and Ramaekers, J. G.\n</span>\n\n  \n\n</span>\n\n  <i>Addict Biol</i>,e12870.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870\"\n     onclick=\"log_download('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/adb.12870\"\n     onclick=\"log_download('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://doi.org/10.1111/adb.12870', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN224,\n   author = {Mason, N. L. and Theunissen, E. L. and Hutten, Nrpw and Tse, D. H. Y. and Toennes, S. W. and Jansen, J. F. A. and Stiers, P. and Ramaekers, J. G.},\n   title = {Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users},\n   journal = {Addict Biol},\n   pages = {e12870},\n   ISSN = {1369-1600 (Electronic)\n1355-6215 (Linking)},\n   DOI = {10.1111/adb.12870},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31865628\nhttps://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870},\n   year = {2019},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf', event);\">\n    Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Mason, N. L.; Kuypers, K. P. C.; Muller, F.; Reckweg, J.; Tse, D. H. Y.; Toennes, S. W.; Hutten, N.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Stiers, P.; Feilding, A.;  and Ramaekers, J. G.\n</span>\n\n  \n\n</span>\n\n  <i>Neuropsychopharmacology</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf\"\n     onclick=\"log_download('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/s41386-020-0718-8\"\n     onclick=\"log_download('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://doi.org/10.1038/s41386-020-0718-8', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN253,\n   author = {Mason, N. L. and Kuypers, K. P. C. and Muller, F. and Reckweg, J. and Tse, D. H. Y. and Toennes, S. W. and Hutten, Nrpw and Jansen, J. F. A. and Stiers, P. and Feilding, A. and Ramaekers, J. G.},\n   title = {Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin},\n   journal = {Neuropsychopharmacology},\n   ISSN = {1740-634X (Electronic)\n0893-133X (Linking)},\n   DOI = {10.1038/s41386-020-0718-8},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32446245\nhttps://www.nature.com/articles/s41386-020-0718-8_reference.pdf},\n   year = {2020},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_f__Advanced_Diffusion_Models\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_f__Advanced_Diffusion_Models')\"\n      onkeypress=\"toggleGroup('group_f__Advanced_Diffusion_Models')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>f) Advanced Diffusion Models</span>\n      <span class=\"bibbase_group_count\">\n        \n        (8)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event);\">\n    On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; van Oostenbrugge, R. J.; Kessels, A. G.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 38(5): 876-82.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc14-2043\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://doi.org/10.2337/dc14-2043', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN67,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Oostenbrugge, R. J. and Kessels, A. G. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes},\n   journal = {Diabetes Care},\n   volume = {38},\n   number = {5},\n   pages = {876-82},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   Abstract = {OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.},\n   DOI = {10.2337/dc14-2043},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25690006},\n   year = {2015},\n   keywords = {a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event);\">\n    On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Backes, W. H.; Zhang, C. E.; Staals, J.; van Oostenbrugge, R. J.; Jeukens, C.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>AJNR Am J Neuroradiol</i>, 39(2): 226-231.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3174/ajnr.A5474\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://doi.org/10.3174/ajnr.A5474', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN95,\n   author = {Wong, S. M. and Backes, W. H. and Zhang, C. E. and Staals, J. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Jansen, J. F. A.},\n   title = {On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease},\n   journal = {AJNR Am J Neuroradiol},\n   volume = {39},\n   number = {2},\n   pages = {226-231},\n   ISSN = {1936-959X (Electronic)\n0195-6108 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were &lt;3.70% in normal-appearing tissue and &lt;9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.},\n   DOI = {10.3174/ajnr.A5474},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29217741},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event);\">\n    Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Zhang, C. E.; van Bussel, F. C.; Staals, J.; Jeukens, C. R.; Hofman, P. A.; van Oostenbrugge, R. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 14: 216-221.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2017.01.017\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://doi.org/10.1016/j.nicl.2017.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN97,\n   author = {Wong, S. M. and Zhang, C. E. and van Bussel, F. C. and Staals, J. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H. and Jansen, J. F.},\n   title = {Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging},\n   journal = {Neuroimage Clin},\n   volume = {14},\n   pages = {216-221},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p &lt; 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p &lt; 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p &lt; 0.024) and D (p &lt; 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.},\n   DOI = {10.1016/j.nicl.2017.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28180080},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event);\">\n    Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; Uiterwijk, R.; Staals, J.; Backes, W. H.; Hoff, E. I.; Schreuder, T.; Jeukens, C. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>;  and van Oostenbrugge, R. J.\n</span>\n\n  \n\n</span>\n\n  <i>Stroke</i>, 48(3): 658-663.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1161/STROKEAHA.116.015084\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://doi.org/10.1161/STROKEAHA.116.015084', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN99,\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Staals, J. and Backes, W. H. and Hoff, E. I. and Schreuder, T. and Jeukens, C. R. and Jansen, J. F. and van Oostenbrugge, R. J.},\n   title = {Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition},\n   journal = {Stroke},\n   volume = {48},\n   number = {3},\n   pages = {658-663},\n   ISSN = {1524-4628 (Electronic)\n0039-2499 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.},\n   DOI = {10.1161/STROKEAHA.116.015084},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28196940},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22826198\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22826198', event);\">\n    Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lu, Y.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Mazaheri, Y.; Stambuk, H. E.; Koutcher, J. A.;  and Shukla-Dave, A.\n</span>\n\n  \n\n</span>\n\n  <i>J Magn Reson Imaging</i>, 36(5): 1088-96.  2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22826198\"\n     onclick=\"log_download('lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22826198', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jmri.23770\"\n     onclick=\"log_download('lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012', 'http://doi.org/10.1002/jmri.23770', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lu-jansen-mazaheri-stambuk-koutcher-shukladave-extensionoftheintravoxelincoherentmotionmodeltonongaussiandiffusioninheadandneckcancer-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN49,\n   author = {Lu, Y. and Jansen, J. F. and Mazaheri, Y. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},\n   title = {Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer},\n   journal = {J Magn Reson Imaging},\n   volume = {36},\n   number = {5},\n   pages = {1088-96},\n   ISSN = {1522-2586 (Electronic)\n1053-1807 (Linking)},\n   Abstract = {PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.},\n   DOI = {10.1002/jmri.23770},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22826198},\n   year = {2012},\n   keywords = {f) Advanced Diffusion Models},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from eight patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the eight neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3-79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20037133\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20037133', event);\">\n    Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Stambuk, H. E.; Koutcher, J. A.;  and Shukla-Dave, A.\n</span>\n\n  \n\n</span>\n\n  <i>AJNR Am J Neuroradiol</i>, 31(4): 741-8.  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20037133\"\n     onclick=\"log_download('jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20037133', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3174/ajnr.A1919\"\n     onclick=\"log_download('jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010', 'http://doi.org/10.3174/ajnr.A1919', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jansen-stambuk-koutcher-shukladave-nongaussiananalysisofdiffusionweightedmrimaginginheadandnecksquamouscellcarcinomaafeasibilitystudy-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN40,\n   author = {Jansen, J. F. and Stambuk, H. E. and Koutcher, J. A. and Shukla-Dave, A.},\n   title = {Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study},\n   journal = {AJNR Am J Neuroradiol},\n   volume = {31},\n   number = {4},\n   pages = {741-8},\n   ISSN = {1936-959X (Electronic)\n0195-6108 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T. Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between K(app) and D(app). RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P &lt; .05). D(app) was approximately twice the value of ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84). K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, K(app), potentially with added value.},\n   DOI = {10.3174/ajnr.A1919},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20037133},\n   year = {2010},\n   keywords = {f) Advanced Diffusion Models},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T. Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between K(app) and D(app). RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). D(app) was approximately twice the value of ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84). K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, K(app), potentially with added value.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf', event);\">\n    Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Backes, W. H.; Drenthen, G. S.; Zhang, C. E.; Voorter, P. H. M.; Staals, J.; van Oostenbrugge, R. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Magn Reson Imaging</i>, 51(4): 1170-1180.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf\"\n     onclick=\"log_download('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31486211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jmri.26920\"\n     onclick=\"log_download('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020', 'http://doi.org/10.1002/jmri.26920', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-backes-drenthen-zhang-voorter-staals-vanoostenbrugge-jansen-spectraldiffusionanalysisofintravoxelincoherentmotionmriincerebralsmallvesseldisease-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN234,\n   author = {Wong, S. M. and Backes, W. H. and Drenthen, G. S. and Zhang, C. E. and Voorter, P. H. M. and Staals, J. and van Oostenbrugge, R. J. and Jansen, J. F. A.},\n   title = {Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease},\n   journal = {J Magn Reson Imaging},\n   volume = {51},\n   number = {4},\n   pages = {1170-1180},\n   ISSN = {1522-2586 (Electronic)\n1053-1807 (Linking)},\n   DOI = {10.1002/jmri.26920},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31486211\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078988/pdf/JMRI-51-1170.pdf},\n   year = {2020},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4', event);\">\n    IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Wong, S. M.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  Volume 1 . IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease, pages 85-98. Le Bihan, D.; Iima, M.; Federau, C.;  and Sigmund, E. E., editor(s). Pan Stanford Publishing Pte. Ltd., Singapore,  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4\"\n     onclick=\"log_download('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1201/9780429427275-4\"\n     onclick=\"log_download('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018', 'http://doi.org/10.1201/9780429427275-4', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>3 downloads</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jansen-wong-backes-ivimmriawindowtothepathophysiologyunderlyingcerebralsmallvesseldisease-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@inbook{RN240,\n   author = {Jansen, J. F. and Wong, S. M. and Backes, W. H.},\n   title = {IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease},\n   booktitle = {Intravoxel Incoherent Motion (IVIM) MRI - Principles and Applications},\n   editor = {Le Bihan, D. and Iima, M. and Federau, C. and Sigmund, E. E.},\n   publisher = {Pan Stanford Publishing Pte. Ltd.},\n   address = {Singapore},\n   volume = {1},\n   chapter = {4},\n   pages = {85-98},\n   ISBN = {9789814800198},\n   DOI = {10.1201/9780429427275-4},\n   url = {https://www.taylorfrancis.com/books/e/9780429427275/chapters/10.1201/9780429427275-4},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models},\n   type = {Book Section}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_g__Brain_Connectivity\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_g__Brain_Connectivity')\"\n      onkeypress=\"toggleGroup('group_g__Brain_Connectivity')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>g) Brain Connectivity</span>\n      <span class=\"bibbase_group_count\">\n        \n        (13)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/26791354', event);\">\n    Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neuroendocrinol</i>, 28(3): 12366.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/26791354\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/26791354', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jne.12366\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016', 'http://doi.org/10.1111/jne.12366', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanboxtel-schram-stehouwer-wildberger-jansen-alteredhippocampalwhitematterconnectivityintype2diabetesmellitusandmemorydecrements-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN66,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Altered Hippocampal White Matter Connectivity in Type 2 Diabetes Mellitus and Memory Decrements},\n   journal = {J Neuroendocrinol},\n   volume = {28},\n   number = {3},\n   pages = {12366},\n   ISSN = {1365-2826 (Electronic)\n0953-8194 (Linking)},\n   Abstract = {Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.},\n   DOI = {10.1111/jne.12366},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/26791354},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes mellitus is associated with cognitive decrements. Specifically affected cognitive domains are learning and memory, for which the hippocampus plays an essential role. The pathophysiological mechanism remains to be revealed. The present study examined whether local hippocampal microstructure and white matter connectivity are related to type 2 diabetes and memory performance. Forty participants with type 2 diabetes and 38 participants without type 2 diabetes underwent detailed cognitive assessment and 3-Tesla diffusion magnetic resonance imaging (MRI). Diffusion MRI was performed to assess microstructure (fractional anisotropy and mean diffusivity) and white matter connectivity (tract volume) of the hippocampus, which were compared between participants with and without type 2 diabetes. No differences in hippocampal microstructure were observed. Participants with type 2 diabetes had fewer white matter connections between the hippocampus and frontal lobe (P = 0.017). Participants who scored lower on memory function, regardless of type 2 diabetes, had fewer white matter connections between the hippocampus and temporal lobe (P = 0.017). Taken together, type 2 diabetes and memory decrements appear to be associated with altered hippocampal white matter connectivity.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27217484', event);\">\n    Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; van Veenendaal, T. M.; Hofman, P. A.; van Boxtel, M. P.; Schram, M. T.; Sep, S. J.; Dagnelie, P. C.; Schaper, N.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes</i>, 65(8): 2404-13.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27217484\"\n     onclick=\"log_download('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27217484', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/db16-0128\"\n     onclick=\"log_download('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016', 'http://doi.org/10.2337/db16-0128', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-vanveenendaal-hofman-vanboxtel-schram-sep-dagnelie-etal-functionalbrainnetworksarealteredintype2diabetesandprediabetessignsforcompensationofcognitivedecrementsthemaastrichtstudy-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN68,\n   author = {van Bussel, F. C. and Backes, W. H. and van Veenendaal, T. M. and Hofman, P. A. and van Boxtel, M. P. and Schram, M. T. and Sep, S. J. and Dagnelie, P. C. and Schaper, N. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study},\n   journal = {Diabetes},\n   volume = {65},\n   number = {8},\n   pages = {2404-13},\n   ISSN = {1939-327X (Electronic)\n0012-1797 (Linking)},\n   Abstract = {Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.},\n   DOI = {10.2337/db16-0128},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27217484},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event);\">\n    High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; Backes, W. H.; Tse, D. H. Y.; Scheenen, T. W. J.; Klomp, D. W.; Hofman, P. A. M.; Rouhl, R. P. W.; Vlooswijk, M. C. G.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 19: 47-55.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.04.006\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://doi.org/10.1016/j.nicl.2018.04.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN83,\n   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},\n   journal = {Neuroimage Clin},\n   volume = {19},\n   pages = {47-55},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the &#x27;neurotransmitter networks&#x27; concept might also provide new insights for other neurological diseases.},\n   DOI = {10.1016/j.nicl.2018.04.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},\n   year = {2018},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20708970', event);\">\n    Functional MRI in chronic epilepsy: associations with cognitive impairment.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; de Krom, M. C.; Majoie, H. M.; Hofman, P. A.; Backes, W. H.;  and Aldenkamp, A. P.\n</span>\n\n  \n\n</span>\n\n  <i>Lancet Neurol</i>, 9(10): 1018-27.  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20708970\"\n     onclick=\"log_download('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20708970', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional MRI in chronic epilepsy: associations with cognitive impairment [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/S1474-4422(10)70180-0\"\n     onclick=\"log_download('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010', 'http://doi.org/10.1016/S1474-4422(10)70180-0', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-dekrom-majoie-hofman-backes-aldenkamp-functionalmriinchronicepilepsyassociationswithcognitiveimpairment-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN90,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and de Krom, M. C. and Majoie, H. M. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P.},\n   title = {Functional MRI in chronic epilepsy: associations with cognitive impairment},\n   journal = {Lancet Neurol},\n   volume = {9},\n   number = {10},\n   pages = {1018-27},\n   ISSN = {1474-4465 (Electronic)\n1474-4422 (Linking)},\n   Abstract = {Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.},\n   DOI = {10.1016/S1474-4422(10)70180-0},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20708970},\n   year = {2010},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Chronic epilepsy is frequently accompanied by serious cognitive side-effects. Clinical factors are important, but cannot account entirely for this cognitive comorbidity. Therefore, research is focusing on the underlying cerebral mechanisms to understand the development of cognitive dysfunction. In the past two decades, functional MRI techniques have been applied extensively to the study of cognitive impairment in chronic epilepsy. However, because of wide variation in study designs, analysis methods, and data presentation, interpretation of these studies has become increasingly difficult for clinicians. In patients with localisation-related epilepsy, whether findings of functional MRI represent the underlying neuronal substrate for cognitive decline remains a subject of debate.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21635235', event);\">\n    Memory processes and prefrontal network dysfunction in cryptogenic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Jeukens, C. R.; Majoie, H. J.; Hofman, P. A.; de Krom, M. C.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsia</i>, 52(8): 1467-75.  2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21635235\"\n     onclick=\"log_download('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21635235', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Memory processes and prefrontal network dysfunction in cryptogenic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/j.1528-1167.2011.03108.x\"\n     onclick=\"log_download('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011', 'http://doi.org/10.1111/j.1528-1167.2011.03108.x', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-jeukens-majoie-hofman-dekrom-aldenkamp-backes-memoryprocessesandprefrontalnetworkdysfunctionincryptogenicepilepsy-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN91,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Jeukens, C. R. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Memory processes and prefrontal network dysfunction in cryptogenic epilepsy},\n   journal = {Epilepsia},\n   volume = {52},\n   number = {8},\n   pages = {1467-75},\n   ISSN = {1528-1167 (Electronic)\n0013-9580 (Linking)},\n   Abstract = {PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.},\n   DOI = {10.1111/j.1528-1167.2011.03108.x},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21635235},\n   year = {2011},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. METHODS: Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. KEY FINDINGS: Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient group. SIGNIFICANCE: Deficits in the processes involved in transient working memory, and to a lesser extent in short-term memory, in patients with localization-related epilepsy of both temporal and extratemporal origin cannot be attributed to hippocampal atrophy or function only, but are also related to reduced functional connectivity in the prefrontal brain. Because patients with symptomatic lesions or mesiotemporal sclerosis were excluded from this study, the results cannot be explained by structural lesions. Therefore, the current findings highlight the influence of epilepsy on the prefrontal network integrity as a possible underlying problem of memory impairment.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20679633', event);\">\n    Functional connectivity and language impairment in cryptogenic localization-related epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Majoie, H. J.; Hofman, P. A.; de Krom, M. C.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 75(5): 395-402.  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/20679633\"\n     onclick=\"log_download('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://www.ncbi.nlm.nih.gov/pubmed/20679633', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional connectivity and language impairment in cryptogenic localization-related epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0b013e3181ebdd3e\"\n     onclick=\"log_download('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010', 'http://doi.org/10.1212/WNL.0b013e3181ebdd3e', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-jansen-majoie-hofman-dekrom-aldenkamp-backes-functionalconnectivityandlanguageimpairmentincryptogeniclocalizationrelatedepilepsy-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN92,\n   author = {Vlooswijk, M. C. and Jansen, J. F. and Majoie, H. J. and Hofman, P. A. and de Krom, M. C. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Functional connectivity and language impairment in cryptogenic localization-related epilepsy},\n   journal = {Neurology},\n   volume = {75},\n   number = {5},\n   pages = {395-402},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.},\n   DOI = {10.1212/WNL.0b013e3181ebdd3e},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/20679633},\n   year = {2010},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21832213', event);\">\n    Loss of network efficiency associated with cognitive decline in chronic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vlooswijk, M. C.; Vaessen, M. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; de Krom, M. C.; Majoie, H. J.; Hofman, P. A.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 77(10): 938-44.  2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21832213\"\n     onclick=\"log_download('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21832213', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Loss of network efficiency associated with cognitive decline in chronic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0b013e31822cfc2f\"\n     onclick=\"log_download('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011', 'http://doi.org/10.1212/WNL.0b013e31822cfc2f', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vlooswijk-vaessen-jansen-dekrom-majoie-hofman-aldenkamp-backes-lossofnetworkefficiencyassociatedwithcognitivedeclineinchronicepilepsy-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN94,\n   author = {Vlooswijk, M. C. and Vaessen, M. J. and Jansen, J. F. and de Krom, M. C. and Majoie, H. J. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Loss of network efficiency associated with cognitive decline in chronic epilepsy},\n   journal = {Neurology},\n   volume = {77},\n   number = {10},\n   pages = {938-44},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.},\n   DOI = {10.1212/WNL.0b013e31822cfc2f},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/21832213},\n   year = {2011},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22056967', event);\">\n    Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van der Kruijs, S. J.; Bodde, N. M.; Vaessen, M. J.; Lazeron, R. H.; Vonck, K.; Boon, P.; Hofman, P. A.; Backes, W. H.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neurol Neurosurg Psychiatry</i>, 83(3): 239-47.  2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22056967\"\n     onclick=\"log_download('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22056967', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1136/jnnp-2011-300776\"\n     onclick=\"log_download('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012', 'http://doi.org/10.1136/jnnp-2011-300776', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanderkruijs-bodde-vaessen-lazeron-vonck-boon-hofman-backes-etal-functionalconnectivityofdissociationinpatientswithpsychogenicnonepilepticseizures-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN79,\n   author = {van der Kruijs, S. J. and Bodde, N. M. and Vaessen, M. J. and Lazeron, R. H. and Vonck, K. and Boon, P. and Hofman, P. A. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F.},\n   title = {Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures},\n   journal = {J Neurol Neurosurg Psychiatry},\n   volume = {83},\n   number = {3},\n   pages = {239-47},\n   ISSN = {1468-330X (Electronic)\n0022-3050 (Linking)},\n   Abstract = {INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven&#x27;s Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).},\n   DOI = {10.1136/jnnp-2011-300776},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22056967},\n   year = {2012},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22038907', event);\">\n    White matter network abnormalities are associated with cognitive decline in chronic epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vaessen, M. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Vlooswijk, M. C.; Hofman, P. A.; Majoie, H. J.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Cereb Cortex</i>, 22(9): 2139-47.  2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22038907\"\n     onclick=\"log_download('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/22038907', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White matter network abnormalities are associated with cognitive decline in chronic epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/cercor/bhr298\"\n     onclick=\"log_download('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012', 'http://doi.org/10.1093/cercor/bhr298', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vaessen-jansen-vlooswijk-hofman-majoie-aldenkamp-backes-whitematternetworkabnormalitiesareassociatedwithcognitivedeclineinchronicepilepsy-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN64,\n   author = {Vaessen, M. J. and Jansen, J. F. and Vlooswijk, M. C. and Hofman, P. A. and Majoie, H. J. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {White matter network abnormalities are associated with cognitive decline in chronic epilepsy},\n   journal = {Cereb Cortex},\n   volume = {22},\n   number = {9},\n   pages = {2139-47},\n   ISSN = {1460-2199 (Electronic)\n1047-3211 (Linking)},\n   Abstract = {Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.},\n   DOI = {10.1093/cercor/bhr298},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22038907},\n   year = {2012},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://www.ncbi.nlm.nih.gov/pubmed/22772649', event);\">\n    Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vaessen, M. J.; Braakman, H. M.; Heerink, J. S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Debeij-van Hall, M. H.; Hofman, P. A.; Aldenkamp, A. P.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Cereb Cortex</i>, 23(8): 1997-2006.  2013.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/22772649\"\n     onclick=\"log_download('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://www.ncbi.nlm.nih.gov/pubmed/22772649', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/cercor/bhs186\"\n     onclick=\"log_download('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013', 'http://doi.org/10.1093/cercor/bhs186', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vaessen-braakman-heerink-jansen-debeijvanhall-hofman-aldenkamp-backes-abnormalmodularorganizationoffunctionalnetworksincognitivelyimpairedchildrenwithfrontallobeepilepsy-2013')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN61,\n   author = {Vaessen, M. J. and Braakman, H. M. and Heerink, J. S. and Jansen, J. F. and Debeij-van Hall, M. H. and Hofman, P. A. and Aldenkamp, A. P. and Backes, W. H.},\n   title = {Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy},\n   journal = {Cereb Cortex},\n   volume = {23},\n   number = {8},\n   pages = {1997-2006},\n   ISSN = {1460-2199 (Electronic)\n1047-3211 (Linking)},\n   Abstract = {Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.},\n   DOI = {10.1093/cercor/bhs186},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/22772649},\n   year = {2013},\n   keywords = {b) Epilepsy, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long', event);\">\n    White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vergoossen, L. W.; Schram, M. T.; de Jong, J. J.; Stehouwer, C. D.; Schaper, N. C.; Henry, R. M.; van der Kallen, C. J.; Dagnelie, P. C.; van Boxtel, M. P.; Eussen, S. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 43(1): 201-208.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long\"\n     onclick=\"log_download('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/31601638 https://care.diabetesjournals.org/content/43/1/201 https://care.diabetesjournals.org/content/43/1/201.long', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc19-0762\"\n     onclick=\"log_download('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020', 'http://doi.org/10.2337/dc19-0762', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vergoossen-schram-dejong-stehouwer-schaper-henry-vanderkallen-dagnelie-etal-whitematterconnectivityabnormalitiesinprediabetesandtype2diabetesthemaastrichtstudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN233,\n   author = {Vergoossen, L. W. and Schram, M. T. and de Jong, J. J. and Stehouwer, C. D. and Schaper, N. C. and Henry, R. M. and van der Kallen, C. J. and Dagnelie, P. C. and van Boxtel, M. P. and Eussen, S. J. and Backes, W. H. and Jansen, J. F.},\n   title = {White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study},\n   journal = {Diabetes Care},\n   volume = {43},\n   number = {1},\n   pages = {201-208},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   DOI = {10.2337/dc19-0762},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31601638\nhttps://care.diabetesjournals.org/content/43/1/201\nhttps://care.diabetesjournals.org/content/43/1/201.long},\n   year = {2020},\n   keywords = {a) Type 2 Diabetes Mellitus, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35920350', event);\">\n    Cognitive resilience depends on white matter connectivity: The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  DeJong, N. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; van Boxtel, M. P. J.; Schram, M. T.; Stehouwer, C. D. A.; Dagnelie, P. C.; van der Kallen, C. J. H.; Kroon, A. A.; Wesselius, A.; Koster, A.; Backes, W. H.;  and Kohler, S.\n</span>\n\n  \n\n</span>\n\n  <i>Alzheimers Dement</i>.  2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35920350\"\n     onclick=\"log_download('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35920350', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Cognitive resilience depends on white matter connectivity: The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/alz.12758\"\n     onclick=\"log_download('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022', 'http://doi.org/10.1002/alz.12758', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('dejong-jansen-vanboxtel-schram-stehouwer-dagnelie-vanderkallen-kroon-etal-cognitiveresiliencedependsonwhitematterconnectivitythemaastrichtstudy-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN307,\n   author = {DeJong, N. R. and Jansen, J. F. A. and van Boxtel, M. P. J. and Schram, M. T. and Stehouwer, C. D. A. and Dagnelie, P. C. and van der Kallen, C. J. H. and Kroon, A. A. and Wesselius, A. and Koster, A. and Backes, W. H. and Kohler, S.},\n   title = {Cognitive resilience depends on white matter connectivity: The Maastricht Study},\n   journal = {Alzheimers Dement},\n   ISSN = {1552-5279 (Electronic)\n1552-5260 (Linking)},\n   DOI = {10.1002/alz.12758},\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35920350},\n   year = {2022},\n   keywords = {c) Alzheimer&#x27;s Disease, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35871335', event);\">\n    Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Backes, W. H.; Freeze, W. M.; Jacobs, H. I. L.; Verheggen, I. C. M.; van Boxtel, M. P. J.; Hoff, E. I.; Verhey, F. R.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Alzheimers Dis</i>.  2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/35871335\"\n     onclick=\"log_download('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'https://www.ncbi.nlm.nih.gov/pubmed/35871335', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer&#x27;s Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3233/JAD-220175\"\n     onclick=\"log_download('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022', 'http://doi.org/10.3233/JAD-220175', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-backes-freeze-jacobs-verheggen-vanboxtel-hoff-verhey-etal-richclubconnectivityofthestructuralcovariancenetworkrelatestomemoryprocessesinmildcognitiveimpairmentandalzheimersdisease-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN305,\n   author = {Drenthen, G. S. and Backes, W. H. and Freeze, W. M. and Jacobs, H. I. L. and Verheggen, I. C. M. and van Boxtel, M. P. J. and Hoff, E. I. and Verhey, F. R. and Jansen, J. F. A.},\n   title = {Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer&#x27;s Disease},\n   journal = {J Alzheimers Dis},\n   ISSN = {1875-8908 (Electronic)\n1387-2877 (Linking)},\n   DOI = {10.3233/JAD-220175},\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/35871335},\n   year = {2022},\n   keywords = {c) Alzheimer&#x27;s Disease, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_h__Cerebrovascular_MRI\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_h__Cerebrovascular_MRI')\"\n      onkeypress=\"toggleGroup('group_h__Cerebrovascular_MRI')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>h) Cerebrovascular MRI</span>\n      <span class=\"bibbase_group_count\">\n        \n        (17)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27920431', event);\">\n    Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; van Bussel, F. C.; van de Haar, H. J.; van Osch, M. J.; Hofman, P. A.; van Boxtel, M. P.; van Oostenbrugge, R. J.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Sci Rep</i>, 6(1): 10.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27920431\"\n     onclick=\"log_download('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27920431', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/s41598-016-0003-6\"\n     onclick=\"log_download('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016', 'http://doi.org/10.1038/s41598-016-0003-6', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jansen-vanbussel-vandehaar-vanosch-hofman-vanboxtel-vanoostenbrugge-schram-etal-cerebralbloodflowbloodsupplyandcognitionintype2diabetesmellitus-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN41,\n   author = {Jansen, J. F. and van Bussel, F. C. and van de Haar, H. J. and van Osch, M. J. and Hofman, P. A. and van Boxtel, M. P. and van Oostenbrugge, R. J. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Backes, W. H.},\n   title = {Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus},\n   journal = {Sci Rep},\n   volume = {6},\n   number = {1},\n   pages = {10},\n   ISSN = {2045-2322 (Electronic)\n2045-2322 (Linking)},\n   Abstract = {We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a &#x27;distributed deviating voxels&#x27; method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total &#x27;distributed deviating voxels&#x27; demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.},\n   DOI = {10.1038/s41598-016-0003-6},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27920431},\n   year = {2016},\n   keywords = {a) Type 2 Diabetes Mellitus, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event);\">\n    On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Bussel, F. C.; Backes, W. H.; Hofman, P. A.; van Oostenbrugge, R. J.; Kessels, A. G.; van Boxtel, M. P.; Schram, M. T.; Stehouwer, C. D.; Wildberger, J. E.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes Care</i>, 38(5): 876-82.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25690006\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25690006', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/dc14-2043\"\n     onclick=\"log_download('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015', 'http://doi.org/10.2337/dc14-2043', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanbussel-backes-hofman-vanoostenbrugge-kessels-vanboxtel-schram-stehouwer-etal-ontheinterplayofmicrovasculatureparenchymaandmemoryintype2diabetes-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN67,\n   author = {van Bussel, F. C. and Backes, W. H. and Hofman, P. A. and van Oostenbrugge, R. J. and Kessels, A. G. and van Boxtel, M. P. and Schram, M. T. and Stehouwer, C. D. and Wildberger, J. E. and Jansen, J. F.},\n   title = {On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes},\n   journal = {Diabetes Care},\n   volume = {38},\n   number = {5},\n   pages = {876-82},\n   ISSN = {1935-5548 (Electronic)\n0149-5992 (Linking)},\n   Abstract = {OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.},\n   DOI = {10.2337/dc14-2043},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25690006},\n   year = {2015},\n   keywords = {a) Type 2 Diabetes Mellitus, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS: Thirty-nine participants with type 2 diabetes (64.5 +/- 6.1 years old) and 34 participants without type 2 diabetes (58.3 +/- 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS: For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS: In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25524876', event);\">\n    Blood-brain barrier impairment in dementia: current and future in vivo assessments.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; Burgmans, S.; Hofman, P. A.; Verhey, F. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurosci Biobehav Rev</i>, 49: 71-81.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25524876\"\n     onclick=\"log_download('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25524876', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment in dementia: current and future in vivo assessments [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neubiorev.2014.11.022\"\n     onclick=\"log_download('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015', 'http://doi.org/10.1016/j.neubiorev.2014.11.022', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-burgmans-hofman-verhey-jansen-backes-bloodbrainbarrierimpairmentindementiacurrentandfutureinvivoassessments-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN71,\n   author = {van de Haar, H. J. and Burgmans, S. and Hofman, P. A. and Verhey, F. R. and Jansen, J. F. and Backes, W. H.},\n   title = {Blood-brain barrier impairment in dementia: current and future in vivo assessments},\n   journal = {Neurosci Biobehav Rev},\n   volume = {49},\n   pages = {71-81},\n   ISSN = {1873-7528 (Electronic)\n0149-7634 (Linking)},\n   Abstract = {Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.},\n   DOI = {10.1016/j.neubiorev.2014.11.022},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/25524876},\n   year = {2015},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Increasing evidence indicates that blood-brain barrier (BBB) impairment may play a role in the pathophysiology of cognitive decline and dementia. In vivo imaging studies are needed to quantify and localize the BBB defects during life, contemplating the circulatory properties. We reviewed the literature for imaging studies investigating BBB impairment in patients suffering from dementia. After selection, 11 imaging studies were included, of which 6 used contrast-enhanced magnetic resonance imaging (MRI), 2 used contrast-enhanced computed tomography (CT), and 3 positron emission tomography (PET). Primarily the MRI studies hint at a subtle increasing permeability of the BBB, particularly in patients already exhibiting cerebrovascular pathology. More elaborate studies are required to provide convincing evidence on BBB impairment in patients with various stages of dementia with and without obvious cerebrovascular pathology. In the future, dynamic contrast enhanced MRI techniques and transport specific imaging using PET may further detail the research on the molecular nature of BBB defects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27243267', event);\">\n    Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; Burgmans, S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; van Osch, M. J.; van Buchem, M. A.; Muller, M.; Hofman, P. A.; Verhey, F. R.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Radiology</i>, 281(2): 527-535.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27243267\"\n     onclick=\"log_download('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27243267', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1148/radiol.2016152244\"\n     onclick=\"log_download('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016', 'http://doi.org/10.1148/radiol.2016152244', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-burgmans-jansen-vanosch-vanbuchem-muller-hofman-verhey-etal-bloodbrainbarrierleakageinpatientswithearlyalzheimerdisease-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN72,\n   author = {van de Haar, H. J. and Burgmans, S. and Jansen, J. F. and van Osch, M. J. and van Buchem, M. A. and Muller, M. and Hofman, P. A. and Verhey, F. R. and Backes, W. H.},\n   title = {Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease},\n   journal = {Radiology},\n   volume = {281},\n   number = {2},\n   pages = {527-535},\n   ISSN = {1527-1315 (Electronic)\n0033-8419 (Linking)},\n   Abstract = {Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P &lt; .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P &lt; .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P &lt; .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.},\n   DOI = {10.1148/radiol.2016152244},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27243267},\n   year = {2016},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27459939', event);\">\n    Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van de Haar, H. J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; van Osch, M. J. P.; van Buchem, M. A.; Muller, M.; Wong, S. M.; Hofman, P. A. M.; Burgmans, S.; Verhey, F. R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurobiol Aging</i>, 45: 190-196.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/27459939\"\n     onclick=\"log_download('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://www.ncbi.nlm.nih.gov/pubmed/27459939', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Neurovascular unit impairment in early Alzheimer&#x27;s disease measured with magnetic resonance imaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neurobiolaging.2016.06.006\"\n     onclick=\"log_download('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016', 'http://doi.org/10.1016/j.neurobiolaging.2016.06.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vandehaar-jansen-vanosch-vanbuchem-muller-wong-hofman-burgmans-etal-neurovascularunitimpairmentinearlyalzheimersdiseasemeasuredwithmagneticresonanceimaging-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN75,\n   author = {van de Haar, H. J. and Jansen, J. F. A. and van Osch, M. J. P. and van Buchem, M. A. and Muller, M. and Wong, S. M. and Hofman, P. A. M. and Burgmans, S. and Verhey, F. R. J. and Backes, W. H.},\n   title = {Neurovascular unit impairment in early Alzheimer&#x27;s disease measured with magnetic resonance imaging},\n   journal = {Neurobiol Aging},\n   volume = {45},\n   pages = {190-196},\n   ISSN = {1558-1497 (Electronic)\n0197-4580 (Linking)},\n   Abstract = {The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer&#x27;s Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.},\n   DOI = {10.1016/j.neurobiolaging.2016.06.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/27459939},\n   year = {2016},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'https://pubs.rsna.org/doi/10.1148/radiol.2017162578', event);\">\n    Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Backes, W. H.; Van Osch, M. J.; Van de Haar, H. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Radiology</i>, 282(3): 924-25.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://pubs.rsna.org/doi/10.1148/radiol.2017162578\"\n     onclick=\"log_download('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'https://pubs.rsna.org/doi/10.1148/radiol.2017162578', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1148/radiol.2017162578\"\n     onclick=\"log_download('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017', 'http://doi.org/10.1148/radiol.2017162578', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('backes-vanosch-vandehaar-jansen-bloodbrainbarrierleakageinearlyalzheimerdiseaseresponse-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN3,\n   author = {Backes, W. H. and Van Osch, M. J. and Van de Haar, H. J. and Jansen, J. F.},\n   title = {Blood-Brain Barrier Leakage in Early Alzheimer Disease, Response},\n   journal = {Radiology},\n   volume = {282},\n   number = {3},\n   pages = {924-25},\n   ISSN = {1527-1315 (Electronic)\n0033-8419 (Linking)},\n   Abstract = {Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). \nModels employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility\n(2). Therefore, we are happy to respond to these comments.},\n   DOI = {10.1148/radiol.2017162578},\n   url = {https://pubs.rsna.org/doi/10.1148/radiol.2017162578},\n   year = {2017},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Dr Lecler and colleagues comment on theoretical aspects of the kinetic modeling used in our study on BBB leakage measurements (1). Models employed in imaging studies are frequently discussed and should always be carefully designed, validated, and tested for reproducibility (2). Therefore, we are happy to respond to these comments.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event);\">\n    On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Backes, W. H.; Zhang, C. E.; Staals, J.; van Oostenbrugge, R. J.; Jeukens, C.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>AJNR Am J Neuroradiol</i>, 39(2): 226-231.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29217741\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29217741', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3174/ajnr.A5474\"\n     onclick=\"log_download('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018', 'http://doi.org/10.3174/ajnr.A5474', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-backes-zhang-staals-vanoostenbrugge-jeukens-jansen-onthereproducibilityofinversionrecoveryintravoxelincoherentmotionimagingincerebrovasculardisease-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN95,\n   author = {Wong, S. M. and Backes, W. H. and Zhang, C. E. and Staals, J. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Jansen, J. F. A.},\n   title = {On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease},\n   journal = {AJNR Am J Neuroradiol},\n   volume = {39},\n   number = {2},\n   pages = {226-231},\n   ISSN = {1936-959X (Electronic)\n0195-6108 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were &lt;3.70% in normal-appearing tissue and &lt;9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.},\n   DOI = {10.3174/ajnr.A5474},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29217741},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 x10(-2) and for parenchymal diffusivity from 7.20 to 9.11 x 10(-4) mm(2)/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 x 10(-2) and 0.10 to 0.37 x 10(-4) mm(2)/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28160347', event);\">\n    Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Staals, J.; Hofman, P. A. M.; van Oostenbrugge, R. J.; Jeukens, C.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>J Magn Reson Imaging</i>, 46(1): 159-166.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28160347\"\n     onclick=\"log_download('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28160347', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jmri.25540\"\n     onclick=\"log_download('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017', 'http://doi.org/10.1002/jmri.25540', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-staals-hofman-vanoostenbrugge-jeukens-backes-measuringsubtleleakageofthebloodbrainbarrierincerebrovasculardiseasewithdcemritestretestreproducibilityanditsinfluencingfactors-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN96,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Staals, J. and Hofman, P. A. M. and van Oostenbrugge, R. J. and Jeukens, Crlpn and Backes, W. H.},\n   title = {Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors},\n   journal = {J Magn Reson Imaging},\n   volume = {46},\n   number = {1},\n   pages = {159-166},\n   ISSN = {1522-2586 (Electronic)\n1053-1807 (Linking)},\n   Abstract = {PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) &lt;/=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV &lt;/=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P &lt; 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P &lt; 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.},\n   DOI = {10.1002/jmri.25540},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28160347},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: Increased blood-brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test-retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. MATERIAL AND METHODS: DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 +/- 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5-25 minutes) on the reproducibility were evaluated in WM and GM. RESULTS: Coefficients of variation (CV) </=14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV </=13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7.10(-3) to 0.4.10(-3) min(-1) in WM (P < 0.01) and 4.4.10(-3) to 0.9.10(-3) min(-1) in GM (P < 0.01) with increasing scan time (range 5-25 minutes). CONCLUSION: Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:159-166.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event);\">\n    Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; Zhang, C. E.; van Bussel, F. C.; Staals, J.; Jeukens, C. R.; Hofman, P. A.; van Oostenbrugge, R. J.; Backes, W. H.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 14: 216-221.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28180080\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28180080', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2017.01.017\"\n     onclick=\"log_download('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017', 'http://doi.org/10.1016/j.nicl.2017.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-zhang-vanbussel-staals-jeukens-hofman-vanoostenbrugge-backes-etal-simultaneousinvestigationofmicrovasculatureandparenchymaincerebralsmallvesseldiseaseusingintravoxelincoherentmotionimaging-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN97,\n   author = {Wong, S. M. and Zhang, C. E. and van Bussel, F. C. and Staals, J. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H. and Jansen, J. F.},\n   title = {Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging},\n   journal = {Neuroimage Clin},\n   volume = {14},\n   pages = {216-221},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p &lt; 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p &lt; 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p &lt; 0.024) and D (p &lt; 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.},\n   DOI = {10.1016/j.nicl.2017.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28180080},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 +/- 11 y) and thirty-nine controls (age 69 +/- 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29572621', event);\">\n    Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; Uiterwijk, R.; Backes, W. H.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Jeukens, C.; van Oostenbrugge, R. J.;  and Staals, J.\n</span>\n\n  \n\n</span>\n\n  <i>Brain Imaging Behav</i>.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29572621\"\n     onclick=\"log_download('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29572621', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s11682-018-9855-7\"\n     onclick=\"log_download('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018', 'http://doi.org/10.1007/s11682-018-9855-7', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-uiterwijk-backes-jansen-jeukens-vanoostenbrugge-staals-bloodbrainbarrierleakageinrelationtowhitematterhyperintensityvolumeandcognitioninsmallvesseldiseaseandnormalaging-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN98,\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Backes, W. H. and Jansen, J. F. A. and Jeukens, Crlpn and van Oostenbrugge, R. J. and Staals, J.},\n   title = {Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging},\n   journal = {Brain Imaging Behav},\n   ISSN = {1931-7565 (Electronic)\n1931-7557 (Linking)},\n   Abstract = {Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.},\n   DOI = {10.1007/s11682-018-9855-7},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29572621},\n   year = {2018},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event);\">\n    Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; Uiterwijk, R.; Staals, J.; Backes, W. H.; Hoff, E. I.; Schreuder, T.; Jeukens, C. R.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>;  and van Oostenbrugge, R. J.\n</span>\n\n  \n\n</span>\n\n  <i>Stroke</i>, 48(3): 658-663.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28196940\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28196940', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1161/STROKEAHA.116.015084\"\n     onclick=\"log_download('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017', 'http://doi.org/10.1161/STROKEAHA.116.015084', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-uiterwijk-staals-backes-hoff-schreuder-jeukens-etal-intravoxelincoherentmotionimaginginsmallvesseldiseasemicrostructuralintegrityandmicrovascularperfusionrelatedtocognition-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN99,\n   author = {Zhang, C. E. and Wong, S. M. and Uiterwijk, R. and Staals, J. and Backes, W. H. and Hoff, E. I. and Schreuder, T. and Jeukens, C. R. and Jansen, J. F. and van Oostenbrugge, R. J.},\n   title = {Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition},\n   journal = {Stroke},\n   volume = {48},\n   number = {3},\n   pages = {658-663},\n   ISSN = {1524-4628 (Electronic)\n0039-2499 (Linking)},\n   Abstract = {BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.},\n   DOI = {10.1161/STROKEAHA.116.015084},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28196940},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, f) Advanced Diffusion Models, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28031395', event);\">\n    Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Zhang, C. E.; Wong, S. M.; van de Haar, H. J.; Staals, J.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F.</a>; Jeukens, C. R.; Hofman, P. A.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 88(5): 426-432.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/28031395\"\n     onclick=\"log_download('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/28031395', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000003556\"\n     onclick=\"log_download('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017', 'http://doi.org/10.1212/WNL.0000000000003556', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhang-wong-vandehaar-staals-jansen-jeukens-hofman-vanoostenbrugge-etal-bloodbrainbarrierleakageismorewidespreadinpatientswithcerebralsmallvesseldisease-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN100,\n   author = {Zhang, C. E. and Wong, S. M. and van de Haar, H. J. and Staals, J. and Jansen, J. F. and Jeukens, C. R. and Hofman, P. A. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {88},\n   number = {5},\n   pages = {426-432},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.},\n   DOI = {10.1212/WNL.0000000000003556},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/28031395},\n   year = {2017},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage. METHODS: We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter. RESULTS: Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions. CONCLUSION: We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275', event);\">\n    Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Hoff, E. I.; Staals, J.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 92(15): e1669-e1677.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000007263\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://doi.org/10.1212/WNL.0000000000007263', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN128,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {92},\n   number = {15},\n   pages = {e1669-e1677},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   Abstract = {OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p &lt; 0.01) and an increase in leakage volume of 0.7% (p &lt; 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 &lt; r &lt; -0.40, p &lt; 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.},\n   DOI = {10.1212/WNL.0000000000007263},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275},\n   year = {2019},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE: To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD). METHODS: Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r. RESULTS: We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (-0.53 < r < -0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03). CONCLUSION: BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/29225580', event);\">\n    Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Schnerr, R. S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Uludag, K.; Hofman, P. A. M.; Wildberger, J. E.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Front Physiol</i>, 8: 961.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\"\n     onclick=\"log_download('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/29225580', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3389/fphys.2017.00961\"\n     onclick=\"log_download('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://doi.org/10.3389/fphys.2017.00961', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN56,\n   author = {Schnerr, R. S. and Jansen, J. F. A. and Uludag, K. and Hofman, P. A. M. and Wildberger, J. E. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect},\n   journal = {Front Physiol},\n   volume = {8},\n   pages = {961},\n   ISSN = {1664-042X (Print)\n1664-042X (Linking)},\n   Abstract = {Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.},\n   DOI = {10.3389/fphys.2017.00961},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29225580},\n   year = {2017},\n   keywords = {i) High Field MR, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event);\">\n    Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Haast, R. A. M.; Ivanov, D.; RJT, I. J.; Sallevelt, S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Smeets, H. J. M.; de Coo, I. F. M.; Formisano, E.;  and Uludag, K.\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 18: 231-244.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.01.017\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://doi.org/10.1016/j.nicl.2018.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN27,\n   author = {Haast, R. A. M. and Ivanov, D. and RJT, I. Jsselstein and Sallevelt, Sceh and Jansen, J. F. A. and Smeets, H. J. M. and de Coo, I. F. M. and Formisano, E. and Uludag, K.},\n   title = {Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study},\n   journal = {Neuroimage Clin},\n   volume = {18},\n   pages = {231-244},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A&gt;G patients&#x27; brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A&gt;G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain&#x27;s state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A&gt;G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A&gt;G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A&gt;G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.},\n   DOI = {10.1016/j.nicl.2018.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447},\n   year = {2018},\n   keywords = {i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long', event);\">\n    Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Wong, S. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Zhang, C. E.; Hoff, E. I.; Staals, J.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurology</i>, 92(15): e1669-e1677.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30867275 https://n.neurology.org/content/92/15/e1669.long', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1212/WNL.0000000000007263\"\n     onclick=\"log_download('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019', 'http://doi.org/10.1212/WNL.0000000000007263', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('wong-jansen-zhang-hoff-staals-vanoostenbrugge-backes-bloodbrainbarrierimpairmentandhypoperfusionarelinkedincerebralsmallvesseldisease-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN226,\n   author = {Wong, S. M. and Jansen, J. F. A. and Zhang, C. E. and Hoff, E. I. and Staals, J. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease},\n   journal = {Neurology},\n   volume = {92},\n   number = {15},\n   pages = {e1669-e1677},\n   ISSN = {1526-632X (Electronic)\n0028-3878 (Linking)},\n   DOI = {10.1212/WNL.0000000000007263},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30867275\nhttps://n.neurology.org/content/92/15/e1669.long},\n   keywords = {d) Cerebral Small Vessel Disease, h) Cerebrovascular MRI},\n   year = {2019},\n   \n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31718926 https://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144421Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&amp;hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0197458019303380&amp;tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client\"\n 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event);\">\n    White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Freeze, W. M.; Jacobs, H. I. L.; de Jong, J. J.; Verheggen, I. C. M.; Gronenschild, E.; Palm, W. M.; Hoff, E. I.; Wardlaw, J. M.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Verhey, F. R.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Neurobiol Aging</i>, 85: 113-122.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31718926 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event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neurobiolaging.2019.09.017\"\n     onclick=\"log_download('freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020', 'http://doi.org/10.1016/j.neurobiolaging.2019.09.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('freeze-jacobs-dejong-verheggen-gronenschild-palm-hoff-wardlaw-etal-whitematterhyperintensitiesmediatetheassociationbetweenbloodbrainbarrierleakageandinformationprocessingspeed-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN229,\n   author = {Freeze, W. M. and Jacobs, H. I. L. and de Jong, J. J. and Verheggen, I. C. M. and Gronenschild, Ehbm and Palm, W. M. and Hoff, E. I. and Wardlaw, J. M. and Jansen, J. F. A. and Verhey, F. R. and Backes, W. H.},\n   title = {White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed},\n   journal = {Neurobiol Aging},\n   volume = {85},\n   pages = {113-122},\n   ISSN = {1558-1497 (Electronic)\n0197-4580 (Linking)},\n   DOI = {10.1016/j.neurobiolaging.2019.09.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31718926\nhttps://pdf.sciencedirectassets.com/271067/1-s2.0-S0197458019X0010X/1-s2.0-S0197458019303380/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144421Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=6650a5a1e25cb66781e4dc396a5b1946a692de246947f606c85c2b133aa9c555&amp;hash=32853b2fb515b3523c9f281606d91b391f05bc615dbbb9bbd4da70855fac47d3&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0197458019303380&amp;tid=spdf-fce9abfa-2520-4d1f-822d-1f5f1e421a36&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client},\n   year = {2020},\n   keywords = {c) Alzheimer&#x27;s Disease, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_i__High_Field_MR\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_i__High_Field_MR')\"\n      onkeypress=\"toggleGroup('group_i__High_Field_MR')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>i) High Field MR</span>\n      <span class=\"bibbase_group_count\">\n        \n        (7)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event);\">\n    High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  van Veenendaal, T. M.; Backes, W. H.; Tse, D. H. Y.; Scheenen, T. W. J.; Klomp, D. W.; Hofman, P. A. M.; Rouhl, R. P. W.; Vlooswijk, M. C. G.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 19: 47-55.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30035001\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/30035001', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.04.006\"\n     onclick=\"log_download('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018', 'http://doi.org/10.1016/j.nicl.2018.04.006', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vanveenendaal-backes-tse-scheenen-klomp-hofman-rouhl-vlooswijk-etal-highfieldimagingoflargescaleneurotransmitternetworksproofofconceptandinitialapplicationtoepilepsy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN83,\n   author = {van Veenendaal, T. M. and Backes, W. H. and Tse, D. H. Y. and Scheenen, T. W. J. and Klomp, D. W. and Hofman, P. A. M. and Rouhl, R. P. W. and Vlooswijk, M. C. G. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy},\n   journal = {Neuroimage Clin},\n   volume = {19},\n   pages = {47-55},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the &#x27;neurotransmitter networks&#x27; concept might also provide new insights for other neurological diseases.},\n   DOI = {10.1016/j.nicl.2018.04.006},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30035001},\n   year = {2018},\n   keywords = {b) Epilepsy, e) Neurotransmitter MR Spectroscopy, i) High Field MR, g) Brain Connectivity},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/29225580', event);\">\n    Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Schnerr, R. S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Uludag, K.; Hofman, P. A. M.; Wildberger, J. E.; van Oostenbrugge, R. J.;  and Backes, W. H.\n</span>\n\n  \n\n</span>\n\n  <i>Front Physiol</i>, 8: 961.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29225580\"\n     onclick=\"log_download('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://www.ncbi.nlm.nih.gov/pubmed/29225580', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3389/fphys.2017.00961\"\n     onclick=\"log_download('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017', 'http://doi.org/10.3389/fphys.2017.00961', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('schnerr-jansen-uludag-hofman-wildberger-vanoostenbrugge-backes-pulsatilityoflenticulostriatearteriesassessedby7teslaflowmrimeasurementreproducibilityandapplicabilitytoagingeffect-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN56,\n   author = {Schnerr, R. S. and Jansen, J. F. A. and Uludag, K. and Hofman, P. A. M. and Wildberger, J. E. and van Oostenbrugge, R. J. and Backes, W. H.},\n   title = {Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect},\n   journal = {Front Physiol},\n   volume = {8},\n   pages = {961},\n   ISSN = {1664-042X (Print)\n1664-042X (Linking)},\n   Abstract = {Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.},\n   DOI = {10.3389/fphys.2017.00961},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29225580},\n   year = {2017},\n   keywords = {i) High Field MR, h) Cerebrovascular MRI},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event);\">\n    Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Haast, R. A. M.; Ivanov, D.; RJT, I. J.; Sallevelt, S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Smeets, H. J. M.; de Coo, I. F. M.; Formisano, E.;  and Uludag, K.\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 18: 231-244.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.01.017\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://doi.org/10.1016/j.nicl.2018.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN27,\n   author = {Haast, R. A. M. and Ivanov, D. and RJT, I. Jsselstein and Sallevelt, Sceh and Jansen, J. F. A. and Smeets, H. J. M. and de Coo, I. F. M. and Formisano, E. and Uludag, K.},\n   title = {Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study},\n   journal = {Neuroimage Clin},\n   volume = {18},\n   pages = {231-244},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A&gt;G patients&#x27; brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A&gt;G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain&#x27;s state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A&gt;G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A&gt;G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A&gt;G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.},\n   DOI = {10.1016/j.nicl.2018.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447},\n   year = {2018},\n   keywords = {i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Vingerhoets, C.; Tse, D. H. Y.; Van Oudenaren, M.; Hernaus, D.; Van Duin, E.; Zinkstok, J.; Ramaekers, J. G.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; McAlonan, G.;  and van Amelsvoort, T.\n</span>\n\n  \n\n</span>\n\n  <i>J Psychopharmacol</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1177/0269881120922977\"\n     onclick=\"log_download('vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020', 'http://doi.org/10.1177/0269881120922977', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('vingerhoets-tse-vanoudenaren-hernaus-vanduin-zinkstok-ramaekers-jansen-etal-glutamatergicandgabaergicreactivityandcognitionin22q112deletionsyndromeandhealthyvolunteersarandomizeddoubleblind7teslapharmacologicalmrsstudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN247,\n   author = {Vingerhoets, C. and Tse, D. H. Y. and Van Oudenaren, M. and Hernaus, D. and Van Duin, E. and Zinkstok, J. and Ramaekers, J. G. and Jansen, J. F. A. and McAlonan, G. and van Amelsvoort, T.},\n   title = {Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: a randomized double-blind 7Tesla pharmacological MRS study.},\n   journal = {J Psychopharmacol},\n   DOI = {10.1177/0269881120922977},\n   year = {2020},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870', event);\">\n    Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Mason, N. L.; Theunissen, E. L.; Hutten, N.; Tse, D. H. Y.; Toennes, S. W.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Stiers, P.;  and Ramaekers, J. G.\n</span>\n\n  \n\n</span>\n\n  <i>Addict Biol</i>,e12870.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870\"\n     onclick=\"log_download('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31865628 https://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/adb.12870\"\n     onclick=\"log_download('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019', 'http://doi.org/10.1111/adb.12870', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('mason-theunissen-hutten-tse-toennes-jansen-stiers-ramaekers-reducedresponsivenessoftherewardsystemisassociatedwithtolerancetocannabisimpairmentinchronicusers-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN224,\n   author = {Mason, N. L. and Theunissen, E. L. and Hutten, Nrpw and Tse, D. H. Y. and Toennes, S. W. and Jansen, J. F. A. and Stiers, P. and Ramaekers, J. G.},\n   title = {Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users},\n   journal = {Addict Biol},\n   pages = {e12870},\n   ISSN = {1369-1600 (Electronic)\n1355-6215 (Linking)},\n   DOI = {10.1111/adb.12870},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/31865628\nhttps://onlinelibrary.wiley.com/doi/full/10.1111/adb.12870},\n   year = {2019},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739', event);\">\n    Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Canjels, L. P. W.; Backes, W. H.; van Veenendaal, T. M.; Vlooswijk, M. C. G.; Hofman, P. A. M.; Aldenkamp, A. P.; Rouhl, R. P. W.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neuroimaging</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739\"\n     onclick=\"log_download('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32472965 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jon.12739\"\n     onclick=\"log_download('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020', 'http://doi.org/10.1111/jon.12739', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>3 downloads</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('canjels-backes-vanveenendaal-vlooswijk-hofman-aldenkamp-rouhl-jansen-volumetricandfunctionalactivitylateralizationinhealthysubjectsandpatientswithfocalepilepsyinitialfindingsina7tmristudy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN257,\n   author = {Canjels, L. P. W. and Backes, W. H. and van Veenendaal, T. M. and Vlooswijk, M. C. G. and Hofman, P. A. M. and Aldenkamp, A. P. and Rouhl, R. P. W. and Jansen, J. F. A.},\n   title = {Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study},\n   journal = {J Neuroimaging},\n   ISSN = {1552-6569 (Electronic)\n1051-2284 (Linking)},\n   DOI = {10.1111/jon.12739},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32472965\nhttps://onlinelibrary.wiley.com/doi/full/10.1111/jon.12739},\n   year = {2020},\n   keywords = {b) Epilepsy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf', event);\">\n    Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Mason, N. L.; Kuypers, K. P. C.; Muller, F.; Reckweg, J.; Tse, D. H. Y.; Toennes, S. W.; Hutten, N.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Stiers, P.; Feilding, A.;  and Ramaekers, J. G.\n</span>\n\n  \n\n</span>\n\n  <i>Neuropsychopharmacology</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf\"\n     onclick=\"log_download('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32446245 https://www.nature.com/articles/s41386-020-0718-8_reference.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/s41386-020-0718-8\"\n     onclick=\"log_download('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020', 'http://doi.org/10.1038/s41386-020-0718-8', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('mason-kuypers-muller-reckweg-tse-toennes-hutten-jansen-etal-memyselfbyeregionalalterationsinglutamateandtheexperienceofegodissolutionwithpsilocybin-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN253,\n   author = {Mason, N. L. and Kuypers, K. P. C. and Muller, F. and Reckweg, J. and Tse, D. H. Y. and Toennes, S. W. and Hutten, Nrpw and Jansen, J. F. A. and Stiers, P. and Feilding, A. and Ramaekers, J. G.},\n   title = {Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin},\n   journal = {Neuropsychopharmacology},\n   ISSN = {1740-634X (Electronic)\n0893-133X (Linking)},\n   DOI = {10.1038/s41386-020-0718-8},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32446245\nhttps://www.nature.com/articles/s41386-020-0718-8_reference.pdf},\n   year = {2020},\n   keywords = {e) Neurotransmitter MR Spectroscopy, i) High Field MR},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_j__Myelin_Imaging\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_j__Myelin_Imaging')\"\n      onkeypress=\"toggleGroup('group_j__Myelin_Imaging')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>j) Myelin Imaging</span>\n      <span class=\"bibbase_group_count\">\n        \n        (6)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event);\">\n    Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Haast, R. A. M.; Ivanov, D.; RJT, I. J.; Sallevelt, S.; <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>; Smeets, H. J. M.; de Coo, I. F. M.; Formisano, E.;  and Uludag, K.\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage Clin</i>, 18: 231-244.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/29868447\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://www.ncbi.nlm.nih.gov/pubmed/29868447', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nicl.2018.01.017\"\n     onclick=\"log_download('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018', 'http://doi.org/10.1016/j.nicl.2018.01.017', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN27,\n   author = {Haast, R. A. M. and Ivanov, D. and RJT, I. Jsselstein and Sallevelt, Sceh and Jansen, J. F. A. and Smeets, H. J. M. and de Coo, I. F. M. and Formisano, E. and Uludag, K.},\n   title = {Anatomic &amp; metabolic brain markers of the m.3243A&gt;G mutation: A multi-parametric 7T MRI study},\n   journal = {Neuroimage Clin},\n   volume = {18},\n   pages = {231-244},\n   ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n   Abstract = {One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A&gt;G patients&#x27; brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A&gt;G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain&#x27;s state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A&gt;G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A&gt;G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A&gt;G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.},\n   DOI = {10.1016/j.nicl.2018.01.017},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447},\n   year = {2018},\n   keywords = {i) High Field MR, h) Cerebrovascular MRI, j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N=22) and healthy controls (N=15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30965132\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30965132', event);\">\n    Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Backes, W. H.; Aldenkamp, A. P.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage</i>, 195: 333-339.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30965132\"\n     onclick=\"log_download('drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30965132', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neuroimage.2019.04.011\"\n     onclick=\"log_download('drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019', 'http://doi.org/10.1016/j.neuroimage.2019.04.011', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-backes-aldenkamp-jansen-applicabilityandreproducibilityof2dmultislicegrasemyelinwaterfractionwithvaryingacquisitionacceleration-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN127,\n   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Jansen, J. F. A.},\n   title = {Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration},\n   journal = {Neuroimage},\n   volume = {195},\n   pages = {333-339},\n   ISSN = {1095-9572 (Electronic)\n1053-8119 (Linking)},\n   Abstract = {Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30min still provides an excellent reproducibility.},\n   Keywords = {Myelin water fraction\nReproducibility\nT2 relaxometry},\n   DOI = {10.1016/j.neuroimage.2019.04.011},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30965132},\n   year = {2019},\n   keywords = {j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30min still provides an excellent reproducibility.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30444019\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30444019', event);\">\n    A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Backes, W. H.; Aldenkamp, A. P.; Op 't Veld, G. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Magn Reson Med</i>, 81(5): 3292-3303.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/30444019\"\n     onclick=\"log_download('drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/30444019', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/mrm.27600\"\n     onclick=\"log_download('drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019', 'http://doi.org/10.1002/mrm.27600', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-backes-aldenkamp-optveld-jansen-anewanalysisapproachfort2relaxometrymyelinwaterquantificationorthogonalmatchingpursuit-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN121,\n   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Op &#x27;t Veld, G. J. and Jansen, J. F. A.},\n   title = {A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit},\n   journal = {Magn Reson Med},\n   volume = {81},\n   number = {5},\n   pages = {3292-3303},\n   ISSN = {1522-2594 (Electronic)\n0740-3194 (Linking)},\n   Abstract = {PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.},\n   Keywords = {T2 relaxometry\nmyelin water fraction\nnonnegative least squares\northogonal matching pursuit},\n   DOI = {10.1002/mrm.27600},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/30444019},\n   year = {2019},\n   keywords = {j) Myelin Imaging},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280', event);\">\n    Lower myelin-water content of the frontal lobe in childhood absence epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Fonseca Wald, E. L. A.; Backes, W. H.; Debeij - Van Hall, M. H. J. A.; Hendriksen, J. G. M.; Aldenkamp, A. P.; Vermeulen, R. J.; Klinkenberg, S.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Epilepsia</i>, 0(0).  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Lower myelin-water content of the frontal lobe in childhood absence epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/epi.16280\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019', 'http://doi.org/10.1111/epi.16280', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-fonsecawald-backes-debeijvanhall-hendriksen-aldenkamp-vermeulen-klinkenberg-etal-lowermyelinwatercontentofthefrontallobeinchildhoodabsenceepilepsy-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN132,\n   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Debeij - Van Hall, M. H. J. A. and Hendriksen, J. G. M. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},\n   title = {Lower myelin-water content of the frontal lobe in childhood absence epilepsy},\n   journal = {Epilepsia},\n   volume = {0},\n   number = {0},\n   ISSN = {0013-9580},\n   Abstract = {Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P &gt; 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.},\n   DOI = {10.1111/epi.16280},\n   url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16280},\n   year = {2019},\n   keywords = {b) Epilepsy, j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Abstract Objective The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. Methods Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. Results The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. Significance The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32255537 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32255537 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707', event);\">\n    Constructing an Axonal-Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Fonseca Wald, E. L. A.; Backes, W. H.; Aldenkamp, A. P.; Vermeulen, R. J.; Debeij-van Hall, M. H.; Klinkenberg, S.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neuroimaging</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32255537 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32255537 https://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Constructing an Axonal-Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jon.12707\"\n     onclick=\"log_download('drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020', 'http://doi.org/10.1111/jon.12707', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-fonsecawald-backes-aldenkamp-vermeulen-debeijvanhall-klinkenberg-jansen-constructinganaxonalspecificmyelindevelopmentalgraphanditsapplicationtochildhoodabsenceepilepsy-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN246,\n   author = {Drenthen, G. S. and Fonseca Wald, E. L. A. and Backes, W. H. and Aldenkamp, A. P. and Vermeulen, R. J. and Debeij-van Hall, M. H. and Klinkenberg, S. and Jansen, J. F. A.},\n   title = {Constructing an Axonal-Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy},\n   journal = {J Neuroimaging},\n   ISSN = {1552-6569 (Electronic)\n1051-2284 (Linking)},\n   DOI = {10.1111/jon.12707},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32255537\nhttps://onlinelibrary.wiley.com/doi/full/10.1111/jon.12707},\n   year = {2020},\n   keywords = {j) Myelin Imaging},\n   type = {Journal Article}\n}\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"drenthen-backes-aldenkamp-vermeulen-klinkenberg-jansen-onthemeritsofnoninvasivemyelinimaginginepilepsyaliteraturereview-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32173402 https://pdf.sciencedirectassets.com/271055/1-s2.0-S0165027020X00069/1-s2.0-S0165027020301096/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144416Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=056b2124d0201d73cff3fdbc8782f9bf757551387d2965706f98fdbe39efd262&amp;hash=4d7f86d5e3129e3315f7b93be2b4b0f22a8ce1e81eed96dd5fceeb7cf5fbaf78&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0165027020301096&amp;tid=spdf-d2d2f778-426e-43b9-9ea8-f8dbd5cf3a81&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'drenthen-backes-aldenkamp-vermeulen-klinkenberg-jansen-onthemeritsofnoninvasivemyelinimaginginepilepsyaliteraturereview-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32173402 https://pdf.sciencedirectassets.com/271055/1-s2.0-S0165027020X00069/1-s2.0-S0165027020301096/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144416Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=056b2124d0201d73cff3fdbc8782f9bf757551387d2965706f98fdbe39efd262&amp;hash=4d7f86d5e3129e3315f7b93be2b4b0f22a8ce1e81eed96dd5fceeb7cf5fbaf78&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0165027020301096&amp;tid=spdf-d2d2f778-426e-43b9-9ea8-f8dbd5cf3a81&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client', event);\">\n    On the merits of non-invasive myelin imaging in epilepsy, a literature review.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Drenthen, G. S.; Backes, W. H.; Aldenkamp, A. P.; Vermeulen, R. J.; Klinkenberg, S.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>J Neurosci Methods</i>,108687.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32173402 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event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"On the merits of non-invasive myelin imaging in epilepsy, a literature review [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.jneumeth.2020.108687\"\n     onclick=\"log_download('drenthen-backes-aldenkamp-vermeulen-klinkenberg-jansen-onthemeritsofnoninvasivemyelinimaginginepilepsyaliteraturereview-2020', 'http://doi.org/10.1016/j.jneumeth.2020.108687', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/drenthen-backes-aldenkamp-vermeulen-klinkenberg-jansen-onthemeritsofnoninvasivemyelinimaginginepilepsyaliteraturereview-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('drenthen-backes-aldenkamp-vermeulen-klinkenberg-jansen-onthemeritsofnoninvasivemyelinimaginginepilepsyaliteraturereview-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN228,\n   author = {Drenthen, G. S. and Backes, W. H. and Aldenkamp, A. P. and Vermeulen, R. J. and Klinkenberg, S. and Jansen, J. F. A.},\n   title = {On the merits of non-invasive myelin imaging in epilepsy, a literature review},\n   journal = {J Neurosci Methods},\n   pages = {108687},\n   ISSN = {1872-678X (Electronic)\n0165-0270 (Linking)},\n   DOI = {10.1016/j.jneumeth.2020.108687},\n   url = {http://www.ncbi.nlm.nih.gov/pubmed/32173402\nhttps://pdf.sciencedirectassets.com/271055/1-s2.0-S0165027020X00069/1-s2.0-S0165027020301096/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEF4aCXVzLWVhc3QtMSJHMEUCIQCQGLYSXBQtb7r4qT6xaeajHMEJn6X2iG8WZ7Vpu8u5MQIgPVGKdIA2FkySMN3tV5iDJKECZpsVyFFnn7STPy7Mk%2FEqtAMIdhADGgwwNTkwMDM1NDY4NjUiDK5vEFyvRtd%2BCavrzSqRA0OF63kv2fsAOKn5lzBazvQ1yL9IkjHlyfXQWjFcvdmRtRiBu4318K2zDokogx4CQbn47M3Gx5tppJhVnhcjAFGxCWXw3PR%2Fw2x2j1VtWVZWPU3fe0lLG7b%2B%2BHGfvaY1L3nAY5mkXF3iNP57UFlAGzhnaj8Nmj2tn5gxzUpRPW2TkNDqI52nJXOh0rP4KwLmtAva2ZfmbO4Z59vpXs%2FB%2FwbfzQaDVQOPcc1OVP29h4PTRKO%2ByHCa9d7W0L0muCaUSkRfN98ZqiYArm6Y605ncr9mDtmDkMlD0TeBMKJ1pg8fIuaApWJCWjwyjO6ZiA3ARle%2BH6EecnASzG1%2FzcedAFwraeiOvkQgcE3thOabOY4DkCa5kijGz31Q%2FW9wSFVZn3IapMwms%2F%2B6124gSXXCtXyNy8SlQrw4B45hM%2BJ88e%2BbepYiuhVc6mwX%2FTNxzqz3A%2Fr01%2Bgn24kL1ou0ee9zRv8xV00ilXIG4vg9%2F9375c%2FT93Bl2VHGftxcddm5zW7MeozVm7o6UDjb3ZS89k%2FMn4QOMKbw1vQFOusB%2FPvv5yV10dZJp4ib90%2BwrNvb6qC3RRTjIYzYDbgqNsem%2BNb3KYh1%2FYp3v8jGG%2BJCmScNCjIyBE2CG%2F2hMNSOxn1OoUlux6ii78X%2BAY7RkHW9mSj1rJnln2oEQkNScHxnNJ%2FNo3ax5qusrILKOw9tHvW9q5ADFKQOUVyoHOUAokB3KVJklHDHlhEFT0PK5Mhxz3Onkx5wpsK%2Fhbg4duEbmCOQN4xvyMGFvkNk9e%2FJuOpG571y6v3An%2FeO1jOyK%2FJXUE6dXWKv1W6P1KqxAAscnr%2Be3EI69v0GtTdE77h57Bs2NPw6z66AX%2FchtQ%3D%3D&amp;X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20200414T144416Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=300&amp;X-Amz-Credential=ASIAQ3PHCVTY2Z7GK7HT%2F20200414%2Fus-east-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=056b2124d0201d73cff3fdbc8782f9bf757551387d2965706f98fdbe39efd262&amp;hash=4d7f86d5e3129e3315f7b93be2b4b0f22a8ce1e81eed96dd5fceeb7cf5fbaf78&amp;host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&amp;pii=S0165027020301096&amp;tid=spdf-d2d2f778-426e-43b9-9ea8-f8dbd5cf3a81&amp;sid=011858f4477d9942d7581a16e4804d44a9c6gxrqb&amp;type=client},\n   year = {2020},\n   keywords = {j) Myelin Imaging},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_k__MRI_quality_control\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_k__MRI_quality_control')\"\n      onkeypress=\"toggleGroup('group_k__MRI_quality_control')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>k) MRI quality control</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/34000406\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021', 'https://www.ncbi.nlm.nih.gov/pubmed/34000406', event);\">\n    Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Monereo-Sanchez, J.; de Jong, J. J. A.; Drenthen, G. S.; Beran, M.; Backes, W. H.; Stehouwer, C. D. A.; Schram, M. T.; Linden, D. E. J.;  and <a class=\"bibbase author link\" href=\"https://www.jansenjfa.com/research/\">Jansen, J. F. A.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neuroimage</i>,118174.  2021.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/34000406\"\n     onclick=\"log_download('monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021', 'https://www.ncbi.nlm.nih.gov/pubmed/34000406', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.neuroimage.2021.118174\"\n     onclick=\"log_download('monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021', 'http://doi.org/10.1016/j.neuroimage.2021.118174', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('monereosanchez-dejong-drenthen-beran-backes-stehouwer-schram-linden-etal-qualitycontrolstrategiesforbrainmrisegmentationandparcellationpracticalapproachesandrecommendationsinsightsfromthemaastrichtstudy-2021')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{RN280,\n   author = {Monereo-Sanchez, J. and de Jong, J. J. A. and Drenthen, G. S. and Beran, M. and Backes, W. H. and Stehouwer, C. D. A. and Schram, M. T. and Linden, D. E. J. and Jansen, J. F. A.},\n   title = {Quality control strategies for brain MRI segmentation and parcellation: practical approaches and recommendations - insights from The Maastricht Study},\n   journal = {Neuroimage},\n   pages = {118174},\n   ISSN = {1095-9572 (Electronic)\n1053-8119 (Linking)},\n   DOI = {10.1016/j.neuroimage.2021.118174},\n   url = {https://www.ncbi.nlm.nih.gov/pubmed/34000406},\n   year = {2021},\n   keywords = {k) MRI quality control},\n   type = {Journal Article}\n}\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n\n\n\n  </div>\n\n\n  <!-- Modal -->\n\n  <!-- <iframe id=\"bibbase_network_frame\" -->\n  <!--         src=\"//bibbase.org/network/control\" -->\n  <!--         style=\"display: none;\"> -->\n  <!-- </iframe> -->\n\n</div>\n"}; document.write(bibbase_data.data);