Advertisement

A Conceivable Mechanism Responsible for the Synergy of High and Low Voltage Irreversible Electroporation Pulses

  • Yanpeng Lv
  • Chenguo YaoEmail author
  • Boris Rubinsky
Article
  • 119 Downloads

Abstract

Irreversible electroporation (IRE), is a new non-thermal tissue ablation technology in which brief high electric field pulses are delivered across the target tissue to induce cell death by irreversible permeabilization of the cell membrane. A deficiency of conventional IRE is that the ablation zone is relatively small, bounded by the irreversible electroporation isoelectric field margin. In the previous studies we have introduced a new treatment protocol that combines few short high voltage (SHV) pulses with long low-voltage (LLV) pulses. In the previous studies, we also have shown that the addition of few SHV pulses increases by almost a factor of two the area ablated by a protocol that employs only the LLV pulses. This study employs potato and gel phantom to generate a plausible explanation for the mechanism. The study provides circumstantial evidence that the mechanism involved is the production of electrolytic compounds by the LLV pulse sequence, which causes tissue ablation beyond the margin of the irreversible electroporation isoelectric field generated by the SHV pulses, presumable to the reversible electroporation isoelectric field margin generated by the SHV pulses.

Keywords

Focal ablation Electroporation Electrolysis High and low voltage pulses Synergistic effect 

Notes

Acknowledgments

The authors thank the Mechanical Engineering Department at UC Berkeley, China Scholarship Council (CSC), the National Natural Science Foundation of China (51877022), and the National Natural Science Foundation of China (51807016) for financial support.

Conflict of interest

BR reports that he is a co-inventor in a patent application entitled “Methods, Systems, and Apparatuses for Tissue Ablation Using Electrolysis and Permeabilization”—US 2016 0296269 A1. The other authors have no conflicts to report.

Supplementary material

10439_2019_2258_MOESM1_ESM.pdf (192 kb)
Supplementary material 1 (PDF 191 kb)

References

  1. 1.
    Al-Sakere, B., F. André, C. Bernat, E. Connault, P. Opolon, R. V. Davalos, B. Rubinsky, and L. M. Mir. Tumor ablation with irreversible electroporation. PLoS ONE 2:e1135, 2007.CrossRefGoogle Scholar
  2. 2.
    Bertacchini, C., P. M. Margotti, E. Bergamini, et al. Irreversible electroporation systems for clinical use. In: Irreversible Electroporation. Berlin: Springer, 2010, pp. 255–272.Google Scholar
  3. 3.
    Bhonsle, S., et al. Characterization of irreversible electroporation ablation with a validated perfused organ model. J. Vasc. Interv. Radiol. 27:1913.e2–1922.e2, 2016.CrossRefGoogle Scholar
  4. 4.
    Bonakdar, M., et al. The feasibility of a smart surgical probe for verification of IRE treatments using electrical impedance spectroscopy. IEEE Trans. Biomed. Eng. 2015.  https://doi.org/10.1109/TBME.2015.2441636.Google Scholar
  5. 5.
    Cheung, W., et al. Irreversible electroporation for unresectable hepatocellular carcinoma: initial experience and review of safety and outcomes. Technol. Cancer Res. Treat. 12:233–241, 2013.CrossRefGoogle Scholar
  6. 6.
    Clayton, K., D. O. Trimmer, M. D. Ankaj Khosla, et al. Minimally invasive percutaneous treatment of small renal tumors with irreversible electroporation: a single-center experience. J. Vasc. Interv. Radiol. 26(10):1465–1471, 2015.CrossRefGoogle Scholar
  7. 7.
    Davalos, R. V., L. M. Mir, and R. Boris. Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 33:223–231, 2005.CrossRefGoogle Scholar
  8. 8.
    Dunki-Jacobs, E. M., et al. Evaluation of thermal injury to liver, pancreas and kidney during irreversible electroporation in an in vivo experimental model. Br. J. Surg. 2014.  https://doi.org/10.1002/bjs.9536.Google Scholar
  9. 9.
    Gehl, J., and G. Sersa. Electrochemotherapy and its clinical applications. In: Handbook of Electroporation, edited by D. Miklavcic. New York: Springer, 2017, pp. 1771–1786.Google Scholar
  10. 10.
    Golberg, A., and M. L. Yarmush. Nonthermal irreversible electroporation: fundamentals, applications, and challenges. IEEE Trans. Biomed. Eng. 2013.  https://doi.org/10.1109/TBME.2013.2238672.Google Scholar
  11. 11.
    Guenther, E., N. Klein, P. Mikus, M. K. Stehling, and B. Rubinsky. Electrical breakdown in tissue electroporation. Biochem. Biophys. Res. Commun. 467:736–741, 2015.CrossRefGoogle Scholar
  12. 12.
    Hjouj, M., and B. Rubinsky. Magnetic resonance imaging characteristics of nonthermal irreversible electroporation in vegetable tissue. J. Membr. Biol. 236:137–146, 2010.CrossRefGoogle Scholar
  13. 13.
    Jourabchi, N., K. Beroukhim, B. A. Tafti, et al. Irreversible electroporation (NanoKnife) in cancer treatment. Gastrointest. Interv. 3(1):8–18, 2014.CrossRefGoogle Scholar
  14. 14.
    Kotnik, T., et al. Cell membrane electroporation—part 1: the phenomenon. IEEE Electr. Insul. Mag. 28:14–23, 2012.CrossRefGoogle Scholar
  15. 15.
    Maglietti, F., S. Michinski, N. Olaiz, M. Castro, C. Suárez, and G. Marshall. The role of Ph fronts in tissue electroporation based treatments. PLoS ONE 8:e80167, 2013.CrossRefGoogle Scholar
  16. 16.
    Marinoa, M., et al. pH fronts and tissue natural buffer interaction in gene electrotransfer Protocols. Electrochim. Acta. 255:463–471, 2017.CrossRefGoogle Scholar
  17. 17.
    Martin, R. C. G. Irreversible electroporation of locally advanced pancreatic head adenocarcinoma. J. Gastrointest. Surg. 17:1850–1856, 2013.CrossRefGoogle Scholar
  18. 18.
    Martin, R. C. G. Use of irreversible electroporation in unresectable pancreatic cancer. Hepatobiliary Surg. Nutr. 4(3):211–215, 2015.Google Scholar
  19. 19.
    Martin, R. C. G. Irreversible electroporation techniques in the treatment of locally advanced liver and pancreatic cancer. In: Handbook of Electroporation, edited by D. Miklavcic. Cham: Springer, 2017, pp. 2001–2015.CrossRefGoogle Scholar
  20. 20.
    Martin, R. C. G., K. McFarland, S. Ellis, and V. Velanovich. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J. Am. Coll. Surg. 2012.  https://doi.org/10.1016/j.jamcollsurg.2012.05.021.Google Scholar
  21. 21.
    Miklavcic, D., et al. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim. Biophys. Acta 1523:73–83, 2000.CrossRefGoogle Scholar
  22. 22.
    Miklovic, T., et al. A comprehensive characterization of parameters affecting high-frequency irreversible electroporation lesions. Ann. Biomed. Eng. 2017.  https://doi.org/10.1007/s10439-017-1889-2.Google Scholar
  23. 23.
    Mir, L. M., et al. Electrochemotherapy, a new antitumor treatment: first clinical trial. C. R. Acad. Sci. Ser. III 313:613–618, 1991.Google Scholar
  24. 24.
    Niessen, C., S. Thumann, L. Beyer, et al. Percutaneous irreversible electroporation: long-term survival analysis of 71 patients with inoperable malignant hepatic tumors. Sci. Rep. 7:43687, 2017.CrossRefGoogle Scholar
  25. 25.
    Nilsson, E., J. Berendson, and E. Fontes. Electrochemical treatment of tumours: a simplified mathematical model. J. Electroanal. Chem. 460:88–99, 1999.CrossRefGoogle Scholar
  26. 26.
    Olaiz, N., et al. Tissue damage modeling in gene electrotransfer: The role of pH. Bioelectrochemistry. 100:105–111, 2014.CrossRefGoogle Scholar
  27. 27.
    Rubinsky, B., G. Onik, and P. Mikus. Irreversible electroporation: a new ablation modality–clinical implications. Technol. Cancer Res. Treat. 6:37–48, 2007.CrossRefGoogle Scholar
  28. 28.
    Rubinsky, L., et al. Electrolytic effects during tissue ablation by electroporation. Technol. Cancer Res. Treat. 15:95–103, 2016.CrossRefGoogle Scholar
  29. 29.
    Sánchez-Velázquez, P., et al. Irreversible electroporation of the liver: Is there a safe limit to the ablation volume? Sci. Rep. 2016.  https://doi.org/10.1038/srep23781.Google Scholar
  30. 30.
    Saulis, G., et al. Changes of the solution pH due to exposure by high-voltage electric pulses. Bioelectrochemistry 67:101–108, 2005.CrossRefGoogle Scholar
  31. 31.
    Scheffer, H. J., et al. Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. J. Vasc. Interv. Radiol. 25:997–1011, 2014.CrossRefGoogle Scholar
  32. 32.
    Scheltema, M. J. V., V. D. B. Willemien, D. M. De Bruin, et al. Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial. BMC Cancer 16(1):299, 2016.CrossRefGoogle Scholar
  33. 33.
    Siddiqui, I. A., et al. High-frequency irreversible electroporation: safety and efficacy of next-generation irreversible electroporation adjacent to critical hepatic structures. Surg. Innov. 2017.  https://doi.org/10.1177/1553350617692202.Google Scholar
  34. 34.
    Silk, M. T., et al. Percutaneous ablation of peribiliary tumors with irreversible electroporation. J. Vasc. Interv. Radiol. 2014.  https://doi.org/10.1016/j.jvir.2013.10.012.Google Scholar
  35. 35.
    Suarez, C., et al. The role of additional pulses in electropermeabilization protocols. PLoS ONE 9:e113413, 2014.CrossRefGoogle Scholar
  36. 36.
    Thomson, K. R., et al. Investigation of the safety of irreversible electroporation in humans. J. Vasc. Interv. Radiol. 22:611–621, 2011.CrossRefGoogle Scholar
  37. 37.
    Thomson, K., et al. Safety of clinical irreversible electroporation. In: Handbook of Electroporation, edited by D. Miklavčič. Cham: Springer, 2017, pp. 2017–2035.CrossRefGoogle Scholar
  38. 38.
    Turjanski, P., et al. pH front tracking in the electrochemical treatment (EChT) of tumors: experiments and simulations. Electrochim. Acta 54(26):6199–6206, 2009.CrossRefGoogle Scholar
  39. 39.
    Turjanski, P., et al. The role of ph fronts in reversible electroporation. PLoS ONE 6:e17303, 2011.CrossRefGoogle Scholar
  40. 40.
    Yao, C., et al. Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses. PLoS ONE 12:e0173181, 2017.CrossRefGoogle Scholar
  41. 41.
    Yao, C., et al. Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy. Sci. Rep. 7:15123, 2017.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  1. 1.College of Electrical EngineeringChongqing UniversityChongqingChina
  2. 2.Department of Mechanical Engineering and Department of BioengineeringUniversity of California BerkeleyBerkeleyUSA

Personalised recommendations