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Tissue Ablation with Irreversible Electroporation

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Abstract

This study introduces a new method for minimally invasive treatment of cancer—the ablation of undesirable tissue through the use of irreversible electroporation. Electroporation is the permeabilization of the cell membrane due to an applied electric field. As a function of the field amplitude and duration, the permeabilization can be reversible or irreversible. Over the last decade, reversible electroporation has been intensively pursued as a very promising technique for the treatment of cancer. It is used in combination with cytotoxic drugs, such as bleomycin, in a technique known as electrochemotherapy. However, irreversible electroporation was completely ignored in cancer therapy. We show through mathematical analysis that irreversible electroporation can ablate substantial volumes of tissue, comparable to those achieved with other ablation techniques, without causing any detrimental thermal effects and without the need of adjuvant drugs. This study suggests that irreversible electroporation may become an important and innovative tool in the armamentarium of surgeons treating cancer.

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References

  1. Baker, P. F., and D. E. Knight. Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes. Nature 276:620–622, 1978.

    Google Scholar 

  2. Boone, K., D. Barber, and B. Brown. Review—Imaging with electricity: Report of the European Concerted Action on Impedance Tomography. J. Med. Eng. Technol. 21:201–232, 1997.

    Article  Google Scholar 

  3. Bown, S. G. Phototherapy of tumors. World J. Surgery 7:700–709, 1983.

    Google Scholar 

  4. Carney, C. K. Mathematical models of bioheat transfer. In: Bioengineering Heat Transfer, edited by Y. I. Choi. Boston: Academic Press, 1992, pp. 19–152.

    Google Scholar 

  5. Chang, D. C., B. M. Chassy, J. A. Saunders, and A. E. Sowers. Guide to Electroporation and Electrofusion. San Diego, CA: Academic Press, 1992, 569 pp.

    Google Scholar 

  6. Crowley, J. M. Electrical breakdown of biomolecular lipid membranes as an electromechanical instability. Biophys. J. 13:711–724, 1973.

    Google Scholar 

  7. Davalos, R. V., B. Rubinsky, and D. M. Otten. A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine. IEEE Trans. Biomed. Eng. 49:400–403, 2002.

    Article  Google Scholar 

  8. Davalos, R. V., B. Rubinsky, and L. M. Mir. Theoretical analysis of the thermal effects during in vivo tissue electroporation. Bioelectrochemistry 61:99–107, 2003.

    Article  Google Scholar 

  9. Davalos, R. V., D. M. Otten, L. M. Mir, and B. Rubinsky. Electrical impedance tomography for imaging tissue electroporation. IEEE Trans. Biomed. Eng. 51(5):761–767, 2004.

    Article  Google Scholar 

  10. Deng, Z. S., and J. Liu. Blood perfusion-based model for characterizing the temperature fluctuations in living tissue. Phys. A STAT Mech. Appl. 300:521–530, 2001.

    Article  MATH  Google Scholar 

  11. Diller, K. R. Modeling of bioheat transfer processes at high and low temperatures. In: Bioengineering Heat Transfer, edited by Y. I. Choi. Boston: Academic Press, 1992, pp. 157–357.

    Google Scholar 

  12. Duck, F. A. Physical Properties of Tissues: A Comprehensive Reference Book. San Diego: Academic Press, 1990.

    Google Scholar 

  13. Eto, T. K., and B. Rubinsky. Bioheat transfer. In: Introduction to Bioengineering, edited by S. A. Berger, W. Goldsmith, and E. R. Lewis. Oxford: Oxford Press, 1996.

    Google Scholar 

  14. Foster, R. S., R. Bihrle, N. T. Sanghvi, F. J. Fry, J. P. Donohue. High-intensity focused ultrasound in the treatment of prostatic disease. Eur. Urol. 23:44–47, 1993.

    Google Scholar 

  15. Gauger, B., and F. W. Bentrup. A study of dielectric membrane breakdown in the Fucus egg. J. Membr. Biol. 48:249–264, 1979.

    Google Scholar 

  16. Gothelf, A., L. M. Mir, and J. Gehl. Electrochemotherapy: Results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat. Rev. 29:371–387, 2003.

    Article  Google Scholar 

  17. Heller, R., R. Gilbert, and M. J. Jaroszeski. Clinical applications of electrochemotherapy. Adv. Drug Deliv. Rev. 35:119–129, 1999.

    Article  Google Scholar 

  18. Henriques, F. C., and A. R. Moritz. Studies in thermal injuries: The predictability and the significance of thermally induced rate processes leading to irreversible epidermal damage. Arch. Pathol. 43:489–502, 1947.

    Google Scholar 

  19. Jaroszeski, M. J., R. Gilbert, C. Nicolau, and R. Heller. In vivo gene delivery by electroporation. Adv. Applic. Electrochem. 35:131–137, 1999.

    Google Scholar 

  20. Joshi, R. P., and K. H. Schoenbach. Mechanism for membrane electroporation irreversibility under high-intensity, ultrashort electrical pulse conditions. Phys. Rev. E 66:052901:1–4, 2002.

    Article  Google Scholar 

  21. Kinosita, K., Jr., and T. Y. Tsong. Hemolysis of human erythrocytes by a transient electric field. Proc. Natl. Acad. Sci. U.S.A. 74:1923–1927, 1977.

    Google Scholar 

  22. Lynn, J. G., R. Zwemer, A. J. Chick, and A. E. Miller. A new method for the generation of use of focused ultrasound in experimental biology. J. Gen. Physiol. 26:179–193, 1942.

    Article  Google Scholar 

  23. Miklavcic, D., D. Semrov, H. Mekid, and L. M. Mir. 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.

    Google Scholar 

  24. Mir, L. M. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry 53:1–10, 2001.

    Article  Google Scholar 

  25. Mir, L. M., and S. Orlowski. Mechanisms of electrochemotherapy. Adv. Drug Deliv. Rev. 35:107–118, 1999.

    Article  Google Scholar 

  26. Mir, L. M., S. Orlowski, J. Belehradek Jr., and C. Paoletti. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur. J. Cancer 27:68–72, 1991.

    Article  Google Scholar 

  27. Mir, L. M., L. F. Glass, G. Sersa, J. Teissie, C. Domenge, D. Miklavcic, M. J. Jaroszeski, S. Orlowski, D. S. Reintgen, Z. Rudolf, M. Belehradek, R. Gilbert, M. P. Rols, J. Belehradek, J. M. Bachaud, R. Deconti, B. Stabuc, M. Cemazar, P. Coninx, and R. Heller. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br. J. Cancer 77:2336–2342, 1998.

    Google Scholar 

  28. Neumann, E., and K. Rosenheck. Permeability changes induced by electric impulses in vesicular membranes. J. Membr. Biol. 10:279–290, 1972.

    Google Scholar 

  29. Neumann, E., A. E. Sowers, and C. A. Jordan. Electroporation and Electrofusion in Cell Biology. New York: Plenum Press, 1989.

    Google Scholar 

  30. Neumann, E., M. Schaefer-Ridder, Y. Wang, and P. H. Hofschneider. Gene transfer into mouse lyoma cells by electroporation in high electric fields. J. EMBO 1:841–845, 1982.

    Google Scholar 

  31. Okino, M., and H. Mohri. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn. J. Cancer Res. 78:1319–1321, 1987.

    Google Scholar 

  32. Onik, G., B. Rubinsky, and E. Al. Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma. Cancer 67:901–907, 1991.

    CAS  Google Scholar 

  33. Onik, G. M., J. K. Cohen, G. D. Reyes, and B. Rubinsky. Transrectal ultrasound-guided percutaneous radical cryosurgical ablation of the prostate. Cancer 72:1291–1299, 1993.

    Google Scholar 

  34. Organ, L. W. Electrophysiological principles of radiofrequency lesion making. Appl. Neurophysiol. 39:69–76, 1976.

    Google Scholar 

  35. Pennes, H. H. Analysis of tissue and arterial blood flow temperatures in the resting forearm. J. Appl. Physiol. 1:93–122, 1948.

    Google Scholar 

  36. Rowan, N. J., S. J. Macgregor, J. G. Anderson, R. A. Fouracre, and O. Farish. Pulsed electric field inactivation of diarrhoeagenic Bacillus cereus through irreversible electroporation. Lett. Appl. Microbiol. 31:110–114, 2000.

    Article  Google Scholar 

  37. Rubinsky, B. Cryosurgery, In: Annual Review of Biomedical Engineering v. 2, edited by M. L. Yarmush, K. R. Diller, M. T. Toner, Palo Alto: Annual Reviews, pp. 157–187, 2002.

    Google Scholar 

  38. Shiina, S., K. Tagawa, Y. Niwa, and E. Al. Percutaneous ethanol injection therapy for hepatocellular carcinoma: Results in 146 patients. Am. J. Roentgenol. 160:1023–1028, 1993.

    Google Scholar 

  39. Somiari, S., J. Glasspool-Malone, J. J. Drabick, R. A. Gilbert, R. Heller, M. J. Jaroszeski, and R. W. Malone. Theory and in vivo application of electroporative gene delivery. Molec. Ther. 2:178–187, 2000.

    Article  Google Scholar 

  40. Suzuki, T., B. Shin, K. Fujikura, T. Matsuzaki, and K. Takata. Direct gene transfer into rat liver cells by in vivo electroporation. FEBS Lett. 425:436–440, 1998.

    Article  Google Scholar 

  41. Tieleman, D. P., H. Leontiadau, A. E. Mark, and S. J. Marrink. Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. J. Am. Chem. Soc. 125:6382–6383, 2003.

    Article  Google Scholar 

  42. Vernhes, M. C., A. Benichou, P. Pernin, P. A. Cabanes, and J. Teissie. Elimination of free-living amoebae in fresh water with pulsed electric fields. Water Res. 36:3429–3438, 2002.

    Article  Google Scholar 

  43. Weaver, J. C., and Y. A. Chizmadzhev. Theory of electroporation: A review. Bioelectrochem. Bioenerg. 41:135–160, 1996.

    Article  Google Scholar 

  44. Zimmermann, U., J. Vienken, and G. Pilwat. Dielectric breakdown of cell membranes. Biophys. J. 14:881–899, 1974.

    Article  Google Scholar 

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Authors and Affiliations

  1. Microsystems and Advanced Concepts Engineering, Sandia National Laboratories, 7011 East Ave, MS 9036, Livermore, CA, 94550

    R. V. Davalos

  2. Vectorology and gene transfer, UMR 8121 CNRS, Institut Gustave-Roussy, Villejuif Cédex, France

    L. M. Mir

  3. Department of Mechanical Engineering, Biomedical Engineering Laboratory, University of California, Berkeley, CA, 94720-1740

    B. Rubinsky

Authors
  1. R. V. Davalos
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  2. L. M. Mir
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  3. B. Rubinsky
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Correspondence to R. V. Davalos.

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Davalos, R.V., Mir, L.M. & Rubinsky, B. Tissue Ablation with Irreversible Electroporation. Ann Biomed Eng 33, 223–231 (2005). https://doi.org/10.1007/s10439-005-8981-8

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  • DOI: https://doi.org/10.1007/s10439-005-8981-8

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