An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields. Lorenzo, M. F., Campelo, S. N., Arroyo, J. P., Aycock, K. N., Hinckley, J., Arena, C. B., Rossmeisl, J. H., & Davalos, R. V. Pharmaceuticals (Basel), 2021. 1424-8247 Lorenzo, Melvin F Orcid: 0000-0002-6518-5398 Campelo, Sabrina N Orcid: 0000-0001-6570-7427 Arroyo, Julio P Orcid: 0000-0003-4690-6337 Aycock, Kenneth N Orcid: 0000-0003-3885-6798 Hinckley, Jonathan Orcid: 0000-0001-9868-1163 Arena, Christopher B Orcid: 0000-0002-9380-1194 Rossmeisl, John H Jr Orcid: 0000-0003-1655-7076 Davalos, Rafael V Orcid: 0000-0003-1503-9509 P01 CA207206/CA/NCI NIH HHS/United States R01 CA213423/CA/NCI NIH HHS/United States R25 GM072767/GM/NIGMS NIH HHS/United States P01CA207206/NH/NIH HHS/United States Journal Article Switzerland 2021/12/29 Pharmaceuticals (Basel). 2021 Dec 20;14(12):1333. doi: 10.3390/ph14121333.doi abstract bibtex The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.
@article{RN110,
author = {Lorenzo, M. F. and Campelo, S. N. and Arroyo, J. P. and Aycock, K. N. and Hinckley, J. and Arena, C. B. and Rossmeisl, J. H., Jr. and Davalos, R. V.},
title = {An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields},
journal = {Pharmaceuticals (Basel)},
volume = {14},
number = {12},
note = {1424-8247
Lorenzo, Melvin F
Orcid: 0000-0002-6518-5398
Campelo, Sabrina N
Orcid: 0000-0001-6570-7427
Arroyo, Julio P
Orcid: 0000-0003-4690-6337
Aycock, Kenneth N
Orcid: 0000-0003-3885-6798
Hinckley, Jonathan
Orcid: 0000-0001-9868-1163
Arena, Christopher B
Orcid: 0000-0002-9380-1194
Rossmeisl, John H Jr
Orcid: 0000-0003-1655-7076
Davalos, Rafael V
Orcid: 0000-0003-1503-9509
P01 CA207206/CA/NCI NIH HHS/United States
R01 CA213423/CA/NCI NIH HHS/United States
R25 GM072767/GM/NIGMS NIH HHS/United States
P01CA207206/NH/NIH HHS/United States
Journal Article
Switzerland
2021/12/29
Pharmaceuticals (Basel). 2021 Dec 20;14(12):1333. doi: 10.3390/ph14121333.},
abstract = {The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.},
keywords = {Evans blue dye
Gadolinium
T1-weighted MRI
blood-brain barrier disruption
electroporation
finite element methods
pulsed field ablation
tissue ablation
treatment planning},
ISSN = {1424-8247 (Print)
1424-8247},
DOI = {10.3390/ph14121333},
year = {2021},
type = {Journal Article}
}
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Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.","keywords":"Evans blue dye Gadolinium T1-weighted MRI blood-brain barrier disruption electroporation finite element methods pulsed field ablation tissue ablation treatment planning","issn":"1424-8247 (Print) 1424-8247","doi":"10.3390/ph14121333","year":"2021","bibtex":"@article{RN110,\n author = {Lorenzo, M. F. and Campelo, S. N. and Arroyo, J. P. and Aycock, K. N. and Hinckley, J. and Arena, C. B. and Rossmeisl, J. H., Jr. and Davalos, R. V.},\n title = {An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields},\n journal = {Pharmaceuticals (Basel)},\n volume = {14},\n number = {12},\n note = {1424-8247\nLorenzo, Melvin F\nOrcid: 0000-0002-6518-5398\nCampelo, Sabrina N\nOrcid: 0000-0001-6570-7427\nArroyo, Julio P\nOrcid: 0000-0003-4690-6337\nAycock, Kenneth N\nOrcid: 0000-0003-3885-6798\nHinckley, Jonathan\nOrcid: 0000-0001-9868-1163\nArena, Christopher B\nOrcid: 0000-0002-9380-1194\nRossmeisl, John H Jr\nOrcid: 0000-0003-1655-7076\nDavalos, Rafael V\nOrcid: 0000-0003-1503-9509\nP01 CA207206/CA/NCI NIH HHS/United States\nR01 CA213423/CA/NCI NIH HHS/United States\nR25 GM072767/GM/NIGMS NIH HHS/United States\nP01CA207206/NH/NIH HHS/United States\nJournal Article\nSwitzerland\n2021/12/29\nPharmaceuticals (Basel). 2021 Dec 20;14(12):1333. doi: 10.3390/ph14121333.},\n abstract = {The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). 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