@article{RN211,
   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},
   note = {Haast, Roy A M
Ivanov, Dimo
IJsselstein, Rutger J T
Sallevelt, Suzanne C E H
Jansen, Jacobus F A
Smeets, Hubert J M
de Coo, Irenaeus F M
Formisano, Elia
Uludag, Kamil
eng
Research Support, Non-U.S. Gov't
Netherlands
2018/06/06 06:00
Neuroimage Clin. 2018 Jan 31;18:231-244. doi: 10.1016/j.nicl.2018.01.017. eCollection 2018.},
   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.},
   keywords = {Adult
Analysis of Variance
Brain/*diagnostic imaging/pathology
*Brain Mapping
Case-Control Studies
Correlation of Data
DNA, Mitochondrial/*genetics
Diabetes Mellitus/etiology
Female
Hearing Loss/etiology
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Middle Aged
Mitochondrial Diseases/complications/*diagnostic imaging/*genetics
Muscular Diseases/etiology
Mutation/*genetics
Young Adult
*15-WLT, 15-Words Learning Task
*7t mri
*ADL, Activities daily life
*ASL, Arterial spin labeling
*Brain
*CBF, Cerebral blood flow
*CN, Caudate nucleus
*CNR, Contrast-to-noise ratio
*CSF, Cerebral spinal fluid
*DN, Dentate nucleus
*EPI, Echo planar imaging
*FWHM, Full-width half maximum
*GM, Gray matter
*GP, Globus pallidus
*IQR, Interquartile range
*LDST, Letter-Digit Substitution test
*Leu, Leucine
*MANOVA, Multivariate analysis of variance
*MELAS, Mitochondrial encephalopathy lactic acidosis and stroke-like episodes
*MIDD, Mitochondrial inherited deafness and diabetes
*Mitochondrial
*NMDAS, Newcastle Mitochondrial Disease Adult Scale
*OXPHOS, Oxidative phosphorylation
*Pu, Putamen
*Quantitative
*RF, Radio frequency
*RN, Red nucleus
*ROI, Region of interest
*SLEs, Stroke-like cortical episodes
*SN, Substantia nigra
*SNR, Signal-to-noise ratio
*T, Tesla
*UECs, Urine epithelial cells
*UHF, Ultra-high field
*WM, White matter
*WMLs, White matter lesions
*cGM, Cortical gray matter
*eTIV, Estimated total intracranial volume
*m.3243A>G
*mtDNA, Mitochondrial DNA},
   ISSN = {2213-1582 (Electronic)
2213-1582 (Linking)},
   DOI = {10.1016/j.nicl.2018.01.017},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984598/pdf/main.pdf},
   year = {2018},
   type = {Journal Article}
}

{"_id":"Rbw3EGchGAfdjMxcy","bibbaseid":"haast-ivanov-rjt-sallevelt-jansen-smeets-decoo-formisano-etal-anatomicmetabolicbrainmarkersofthem3243agmutationamultiparametric7tmristudy-2018","downloads":0,"creationDate":"2018-08-03T14:29:50.089Z","title":"Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study","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."],"year":2018,"bibtype":"article","biburl":"https://raw.githubusercontent.com/jansenjfa1/bibbase.github.io/master/jansenjfa.bib","bibdata":{"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","note":"Haast, Roy A M Ivanov, Dimo IJsselstein, Rutger J T Sallevelt, Suzanne C E H Jansen, Jacobus F A Smeets, Hubert J M de Coo, Irenaeus F M Formisano, Elia Uludag, Kamil eng Research Support, Non-U.S. Gov't Netherlands 2018/06/06 06:00 Neuroimage Clin. 2018 Jan 31;18:231-244. doi: 10.1016/j.nicl.2018.01.017. eCollection 2018.","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.","keywords":"Adult Analysis of Variance Brain/*diagnostic imaging/pathology *Brain Mapping Case-Control Studies Correlation of Data DNA, Mitochondrial/*genetics Diabetes Mellitus/etiology Female Hearing Loss/etiology Humans Image Processing, Computer-Assisted Magnetic Resonance Imaging Male Middle Aged Mitochondrial Diseases/complications/*diagnostic imaging/*genetics Muscular Diseases/etiology Mutation/*genetics Young Adult *15-WLT, 15-Words Learning Task *7t mri *ADL, Activities daily life *ASL, Arterial spin labeling *Brain *CBF, Cerebral blood flow *CN, Caudate nucleus *CNR, Contrast-to-noise ratio *CSF, Cerebral spinal fluid *DN, Dentate nucleus *EPI, Echo planar imaging *FWHM, Full-width half maximum *GM, Gray matter *GP, Globus pallidus *IQR, Interquartile range *LDST, Letter-Digit Substitution test *Leu, Leucine *MANOVA, Multivariate analysis of variance *MELAS, Mitochondrial encephalopathy lactic acidosis and stroke-like episodes *MIDD, Mitochondrial inherited deafness and diabetes *Mitochondrial *NMDAS, Newcastle Mitochondrial Disease Adult Scale *OXPHOS, Oxidative phosphorylation *Pu, Putamen *Quantitative *RF, Radio frequency *RN, Red nucleus *ROI, Region of interest *SLEs, Stroke-like cortical episodes *SN, Substantia nigra *SNR, Signal-to-noise ratio *T, Tesla *UECs, Urine epithelial cells *UHF, Ultra-high field *WM, White matter *WMLs, White matter lesions *cGM, Cortical gray matter *eTIV, Estimated total intracranial volume *m.3243A>G *mtDNA, Mitochondrial DNA","issn":"2213-1582 (Electronic) 2213-1582 (Linking)","doi":"10.1016/j.nicl.2018.01.017","url":"http://www.ncbi.nlm.nih.gov/pubmed/29868447 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984598/pdf/main.pdf","year":"2018","bibtex":"@article{RN211,\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 note = {Haast, Roy A M\nIvanov, Dimo\nIJsselstein, Rutger J T\nSallevelt, Suzanne C E H\nJansen, Jacobus F A\nSmeets, Hubert J M\nde Coo, Irenaeus F M\nFormisano, Elia\nUludag, Kamil\neng\nResearch Support, Non-U.S. Gov't\nNetherlands\n2018/06/06 06:00\nNeuroimage Clin. 2018 Jan 31;18:231-244. doi: 10.1016/j.nicl.2018.01.017. eCollection 2018.},\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 keywords = {Adult\nAnalysis of Variance\nBrain/*diagnostic imaging/pathology\n*Brain Mapping\nCase-Control Studies\nCorrelation of Data\nDNA, Mitochondrial/*genetics\nDiabetes Mellitus/etiology\nFemale\nHearing Loss/etiology\nHumans\nImage Processing, Computer-Assisted\nMagnetic Resonance Imaging\nMale\nMiddle Aged\nMitochondrial Diseases/complications/*diagnostic imaging/*genetics\nMuscular Diseases/etiology\nMutation/*genetics\nYoung Adult\n*15-WLT, 15-Words Learning Task\n*7t mri\n*ADL, Activities daily life\n*ASL, Arterial spin labeling\n*Brain\n*CBF, Cerebral blood flow\n*CN, Caudate nucleus\n*CNR, Contrast-to-noise ratio\n*CSF, Cerebral spinal fluid\n*DN, Dentate nucleus\n*EPI, Echo planar imaging\n*FWHM, Full-width half maximum\n*GM, Gray matter\n*GP, Globus pallidus\n*IQR, Interquartile range\n*LDST, Letter-Digit Substitution test\n*Leu, Leucine\n*MANOVA, Multivariate analysis of variance\n*MELAS, Mitochondrial encephalopathy lactic acidosis and stroke-like episodes\n*MIDD, Mitochondrial inherited deafness and diabetes\n*Mitochondrial\n*NMDAS, Newcastle Mitochondrial Disease Adult Scale\n*OXPHOS, Oxidative phosphorylation\n*Pu, Putamen\n*Quantitative\n*RF, Radio frequency\n*RN, Red nucleus\n*ROI, Region of interest\n*SLEs, Stroke-like cortical episodes\n*SN, Substantia nigra\n*SNR, Signal-to-noise ratio\n*T, Tesla\n*UECs, Urine epithelial cells\n*UHF, Ultra-high field\n*WM, White matter\n*WMLs, White matter lesions\n*cGM, Cortical gray matter\n*eTIV, Estimated total intracranial volume\n*m.3243A>G\n*mtDNA, Mitochondrial DNA},\n ISSN = {2213-1582 (Electronic)\n2213-1582 (Linking)},\n DOI = {10.1016/j.nicl.2018.01.017},\n url = {http://www.ncbi.nlm.nih.gov/pubmed/29868447\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984598/pdf/main.pdf},\n year = {2018},\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. 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