Finite Element Analysis of Tissue Conductivity during High-frequency and Low-voltage Irreversible Electroporation

Document Type : Original Paper

Authors

1 Dept. of Medical Physics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Medical Physics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Abstract

Introduction: Irreversible electroporation (IRE) is a process in which the membrane of the cancer cells are irreversibly damaged with the use of high-intensity electric pulses, which in turn leads to cell death. The IRE is a non-thermal way to ablate the cancer cells. This process relies on the distribution of the electric field, which affects the pulse amplitude, width, and electrical conductivity of the tissues. The present study aimed to investigate the relationship of the pulse width and intensity with the conductivity changes during the IRE using simulation.
Materials and Methods: For the purpose of the study, the COMSOL 5 software was utilized to predict the conductivity changes during the IRE. We used 4,000 bipolar and monopolar pulses with the frequency of 5 kHz and 1 Hz, width of 100 µs, and electric fields of low and high intensity. Subsequently, we built three-dimensional numerical models for the liver tissue.
Results: The results of our study revealed that the conductivity of tissue increased during the application of electrical pulses. Additionally, the conductivity changes increased with the elevation of the electric field intensity.
Conclusion: As the finding of this study indicated, the IRE with high-frequency and low electric field intensity could change the tissue conductivity. Therefore, the IRE was recommended to be applied with high frequency and low voltage. 

Keywords

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    1. Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1982;1(7):841.
    2. DeBruin KA, Krassowska W. Modeling electroporation in a single cell. I. Effects of fielstrength and rest potential. Biophys. J. 1999 Sep 30;77(3):1213-24. DOI: 10.1016/S0006-3495(99)76973-0.
    3. Adeyanju O, Al-Angari H, Sahakian A. The optimization of needle electrode number and placement for IRE of hepatocellular carcinoma. Radiol Oncol. 2012 Jun 1;46(2):126-35. DOI: 10.2478/v10019-012-0026-y.
    4. Miklavčič D, Beravs K, Šemrov D, Čemažar M, Demšar F, Serša G. The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys. J. 1998 May 31;74(5):2152-8. DOI: 10.1016/S0006-3495(98)77924-X.
    5. Lu DS, Kee ST, Lee EW. IRE: ready for prime time? Tech Vasc Interv Radiol. 2013;16(4):277-86. DOI: 10.1053/j.tvir.2013.08.010.
    6. Mir LM. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry. 2001 Jan 1;53(1):1-0. DOI: 10.1016/S0302-4598(00)00112-4.
    7. Arena CB, Sano MB, Rossmeisl JH, Caldwell JL, Garcia PA, Rylander MN, et al. High-frequency IRE (H-FIRE) for non-thermal ablation without muscle contraction. Biomed Eng Online. 2011;10(1):102. DOI: 10.1186/1475-925X-10-102.
    8. Reilly JP, Freeman VT, Larkin WD. Sensory effects of transient electrical stimulation-evaluation with a neuroelectric model. IEEE Trans. Biomed. Eng. 1985 Dec(12):1001-11. DOI: 10.1109/TBME.1985.325509.
    9. Miklavcic D, Pucihar G, Pavlovec M, Ribaric S, Mali M, Macek-Lebar A, et al. The effect of high frequency electric pulses on muscle contractions and antitumor efficiency in vivo for a potential use in clinical electrochemotherapy. Bioelectrochemistry. 2005;65(2):121-8. DOI: 10.1016/j.bioelechem.2004.07.004.
    10. Corovic S, Zupanic A, Miklavcic D. Numerical modeling and optimization of electric field distribution in subcutaneous tumor treated with electrochemotherapy using needle electrodes. IEEE Trans. Plasma Sci. 2008 Aug;36(4):1665-72. DOI: 10.1109/TPS.2008.2000996.
    11. Dunki-Jacobs EM, Philips P, Martin RC. Evaluation of resistance as a measure of successful tumor ablation during IRE of the pancreas. J. Am. Coll. Surg. 2014 Feb 28;218(2):179-87. DOI: 10.1016/j.jamcollsurg.2013.10.013.
    12. Moisescu MG, Radu M, Kovacs E, Mir LM, Savopol T. Changes of cell electrical parameters induced by electroporation. A dielectrophoresis study. Biochim. Biophys. Acta. 2013 Feb 28;1828(2):365-72. DOI: 10.1016/j.bbamem.2012.08.030.
    13. Kranjc M, Bajd F, Serša I, Miklavčič D. Magnetic resonance electrical impedance tomography for measuring electrical conductivity during electroporation. Physiol Meas. 2014 May 20;35(6):985.
    14. Ivorra A, Rubinsky B. In vivo electrical impedance measurements during and after electroporation of rat liver. Bioelectrochemistry. 2007 May 31;70(2):287-95. DOI: 10.1016/j.bioelechem.2006.10.005.
    15. Pavlin M, Kandušer M, Reberšek M, Pucihar G, Hart FX, Magjarevićcacute R, et al. Effect of cell electroporation on the conductivity of a cell suspension. Biophys. J. 2005 Jun 30;88(6):4378-90. DOI: 10.1529/biophysj.104.048975.
    16. Cukjati D, Batiuskaite D, André F, Miklavčič D, Mir LM. Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry. 2007 May 31;70(2):501-7. DOI: 10.1016/j.bioelechem.2006.11.001.
    17. Glahder J, Norrild B, Persson MB, Persson BR. Transfection of HeLa‐cells with pEGFP plasmid by impedance power‐assisted electroporation. Biotechnol. Bioeng. 2005 Nov 5;92(3):267-76. DOI: 10.1002/bit.20426.
    18. Garcia PA, Rossmeisl Jr JH, Neal II RE, Ellis TL, Olson JD, Henao-Guerrero N, et al. Intracranial nonthermal IRE: in vivo analysis. J. Membr. Biol. 2010 Jul 1;236(1):127-36. DOI: 10.1007/s00s232-010-9284-z.
    19. Sano MB, Neal RE, Garcia PA, Gerber D, Robertson J, Davalos RV. Towards the creation of decellularized organ constructs using IRE and active mechanical perfusion. Biomed Eng Online. 2010 Dec 10;9(1):83. DOI: 10.1186/1475-925X-9-83.
    20. Garcia PA, Davalos RV, Miklavcic D. A numerical investigation of the electric and thermal cell kill distributions in electroporation-based therapies in tissue. PloS one. 2014 Aug 12;9(8):e103083. DOI: 10.1371/journal.pone.0103083.
    21. Shankayi Z, Firoozabadi SM, Hassan ZS. Optimization of Electric Pulse Amplitude and Frequency In Vitro for Low Voltage and High Frequency Electrochemotherapy. The Journal of membrane biology. 2014 Feb 1;247(2):147-54. DOI: 10.1007/s00232-013-9617-9.
    22. Shankayi Z, Saraf Hassan Z. Comparison of low voltage amplitude electrochemotherapy with 1 Hz and 5 kHz frequency in volume reduction of mouse mammary tumor in Balb/c Mice. Koomesh. 2012 Jun 15;13(4):486-90.
    23. Shankayi Z, Firoozabadi SM, Saraf HZ. The Endothelial Permeability Increased by Low Voltage and High Frequency Electroporation. Journal of biomedical physics & engineering. 2013 Sep;3(3):87.
    24. Bilska AO, DeBruin KA, Krassowska W. Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation. Bioelectrochemistry. 2000 Jun 30;51(2):133-43. DOI: 10.1016/S0302-4598(00)00066-0.