High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction. Arena, C. B., Sano, M. B., Rossmeisl, J. H., Caldwell, J. L., Garcia, P. A., Rylander, M. N., & Davalos, R. V. Biomed Eng Online, 10:102, 2011. 1475-925x Arena, Christopher B Sano, Michael B Rossmeisl, John H Jr Caldwell, John L Garcia, Paulo A Rylander, Marissa Nichole Davalos, Rafael V Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2011/11/23 Biomed Eng Online. 2011 Nov 21;10:102. doi: 10.1186/1475-925X-10-102.doi abstract bibtex BACKGROUND: Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. METHODS: A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. RESULTS: No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. CONCLUSIONS: H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
@article{RN215,
author = {Arena, C. B. and Sano, M. B. and Rossmeisl, J. H., Jr. and Caldwell, J. L. and Garcia, P. A. and Rylander, M. N. and Davalos, R. V.},
title = {High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction},
journal = {Biomed Eng Online},
volume = {10},
pages = {102},
note = {1475-925x
Arena, Christopher B
Sano, Michael B
Rossmeisl, John H Jr
Caldwell, John L
Garcia, Paulo A
Rylander, Marissa Nichole
Davalos, Rafael V
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
England
2011/11/23
Biomed Eng Online. 2011 Nov 21;10:102. doi: 10.1186/1475-925X-10-102.},
abstract = {BACKGROUND: Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. METHODS: A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. RESULTS: No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. CONCLUSIONS: H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.},
keywords = {Ablation Techniques/*adverse effects
Animals
Brain/physiology
Electroporation/*methods
Finite Element Analysis
Male
Membrane Potentials
*Muscle Contraction
Rats
Temperature},
ISSN = {1475-925x},
DOI = {10.1186/1475-925x-10-102},
year = {2011},
type = {Journal Article}
}
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A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. RESULTS: No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. CONCLUSIONS: H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.","keywords":"Ablation Techniques/*adverse effects Animals Brain/physiology Electroporation/*methods Finite Element Analysis Male Membrane Potentials *Muscle Contraction Rats Temperature","issn":"1475-925x","doi":"10.1186/1475-925x-10-102","year":"2011","bibtex":"@article{RN215,\n author = {Arena, C. B. and Sano, M. B. and Rossmeisl, J. H., Jr. and Caldwell, J. L. and Garcia, P. A. and Rylander, M. N. and Davalos, R. V.},\n title = {High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction},\n journal = {Biomed Eng Online},\n volume = {10},\n pages = {102},\n note = {1475-925x\nArena, Christopher B\nSano, Michael B\nRossmeisl, John H Jr\nCaldwell, John L\nGarcia, Paulo A\nRylander, Marissa Nichole\nDavalos, Rafael V\nJournal Article\nResearch Support, Non-U.S. Gov't\nResearch Support, U.S. Gov't, Non-P.H.S.\nEngland\n2011/11/23\nBiomed Eng Online. 2011 Nov 21;10:102. doi: 10.1186/1475-925X-10-102.},\n abstract = {BACKGROUND: Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. METHODS: A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. RESULTS: No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. CONCLUSIONS: H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. 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