Rapid Impedance Spectroscopy for Monitoring Tissue Impedance, Temperature, and Treatment Outcome During Electroporation-Based Therapies. Lorenzo, M. F., Bhonsle, S. P., Arena, C. B., & Davalos, R. V. IEEE Trans Biomed Eng, 68(5):1536-1546, 2021. 1558-2531 Lorenzo, Melvin F Bhonsle, Suyashree P Arena, Christopher B Davalos, Rafael V P30 CA012197/CA/NCI NIH HHS/United States R01 CA240476/CA/NCI NIH HHS/United States P01 CA207206/CA/NCI NIH HHS/United States R43 CA233158/CA/NCI NIH HHS/United States R01 CA213423/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2020/11/07 IEEE Trans Biomed Eng. 2021 May;68(5):1536-1546. doi: 10.1109/TBME.2020.3036535. Epub 2021 Apr 21.
doi  abstract   bibtex   
OBJECTIVE: Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue; this results in changes in electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time ( ∼ 10 s); this timeframe is much larger than pulse periods used with EBTs ( ∼ 1 s). In this study, we utilize rapid EIS techniques to develop a methodology for characterizing electroporation (EP) and thermal effects associated with high-frequency irreversible EP (H-FIRE) in real-time by monitoring inter-burst impedance changes. METHODS: A charge-balanced, bipolar rectangular chirp signal is proposed for rapid EIS. Validation of rapid EIS measurements against a commercial potentiostat was conducted in potato tissue using flat-plate electrodes and thereafter for the measurement of impedance changes throughout IRE treatment. Flat-plate electrodes were then utilized to uniformly heat potato tissue; throughout high-voltage H-FIRE treatment, low-voltage inter-burst impedance measurements were used to continually monitor impedance change and to identify a frequency at which thermal effects are delineated from EP effects. RESULTS: Inter-burst impedance measurements (1.8 kHz - 4.93 MHz) were accomplished at 216 discrete frequencies. Impedance measurements at frequencies above ∼ 1 MHz served to delineate thermal and EP effects in measured impedance. CONCLUSION: We demonstrate rapid-capture ( 1 s) EIS which enables monitoring of inter-burst impedance in real-time. For the first time, we show impedance analysis at high frequencies can delineate thermal effects from EP effects in measured impedance. SIGNIFICANCE: The proposed waveform demonstrates the potential to perform inter-burst EIS using PEFs compatible with existing pulse generator topologies.
@article{RN125,
   author = {Lorenzo, M. F. and Bhonsle, S. P. and Arena, C. B. and Davalos, R. V.},
   title = {Rapid Impedance Spectroscopy for Monitoring Tissue Impedance, Temperature, and Treatment Outcome During Electroporation-Based Therapies},
   journal = {IEEE Trans Biomed Eng},
   volume = {68},
   number = {5},
   pages = {1536-1546},
   note = {1558-2531
Lorenzo, Melvin F
Bhonsle, Suyashree P
Arena, Christopher B
Davalos, Rafael V
P30 CA012197/CA/NCI NIH HHS/United States
R01 CA240476/CA/NCI NIH HHS/United States
P01 CA207206/CA/NCI NIH HHS/United States
R43 CA233158/CA/NCI NIH HHS/United States
R01 CA213423/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2020/11/07
IEEE Trans Biomed Eng. 2021 May;68(5):1536-1546. doi: 10.1109/TBME.2020.3036535. Epub 2021 Apr 21.},
   abstract = {OBJECTIVE: Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue; this results in changes in electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time (  ∼ 10 s); this timeframe is much larger than pulse periods used with EBTs (  ∼ 1 s). In this study, we utilize rapid EIS techniques to develop a methodology for characterizing electroporation (EP) and thermal effects associated with high-frequency irreversible EP (H-FIRE) in real-time by monitoring inter-burst impedance changes. METHODS: A charge-balanced, bipolar rectangular chirp signal is proposed for rapid EIS. Validation of rapid EIS measurements against a commercial potentiostat was conducted in potato tissue using flat-plate electrodes and thereafter for the measurement of impedance changes throughout IRE treatment. Flat-plate electrodes were then utilized to uniformly heat potato tissue; throughout high-voltage H-FIRE treatment, low-voltage inter-burst impedance measurements were used to continually monitor impedance change and to identify a frequency at which thermal effects are delineated from EP effects. RESULTS: Inter-burst impedance measurements (1.8 kHz - 4.93 MHz) were accomplished at 216 discrete frequencies. Impedance measurements at frequencies above  ∼ 1 MHz served to delineate thermal and EP effects in measured impedance. CONCLUSION: We demonstrate rapid-capture ( 1 s) EIS which enables monitoring of inter-burst impedance in real-time. For the first time, we show impedance analysis at high frequencies can delineate thermal effects from EP effects in measured impedance. SIGNIFICANCE: The proposed waveform demonstrates the potential to perform inter-burst EIS using PEFs compatible with existing pulse generator topologies.},
   keywords = {*Dielectric Spectroscopy
Electric Impedance
*Electroporation
Temperature
Treatment Outcome},
   ISSN = {0018-9294 (Print)
0018-9294},
   DOI = {10.1109/tbme.2020.3036535},
   year = {2021},
   type = {Journal Article}
}

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