Cell Electroporation Mechanisms and Preclinical Foundation for Focal Therapy

Chapter
First Online:
Part of the Current Clinical Urology book series (CCU)

Abstract

Irreversible electroporation (IRE) is a novel, nonthermal, minimally invasive ablation technique which employs short electrical pulses between electrode pairs that have been placed into targeted tissue. IRE results in increased permeability of cell membranes within the targeted tissue resulting in cell death through a loss of homeostasis due to the creation of permanent pores in the membranes. A detailed discussion of the effects of increased transmembrane potentials on the disruption of lipid bilayers is provided. Significant preclinical work in focal prostate ablation in canine prostates has been performed to date in which the safety and feasibility of this ablation modality has been validated. Several histopathological staining techniques and scanning electron microscopy (SEM) imaging have been successfully employed to ascertain the outcome of the various preclinical studies conducted with IRE in prostatic and other tissues. Preclinical data is also provided for preservation of critical structures such as neurovascular bundles, blood vessels, and the urethra. A favorable safety and side-effect profile has emerged in which animals survive ablation procedures, recover well, and remain potent post-ablation.

Keywords

Electric Field Strength Electric Field Distribution Radio Frequency Ablation Pancuronium Bromide Histiocytic Sarcoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgements

The authors acknowledge Dr. Paulo A. Garcia and Chris Arena for help with technical editing of the manuscript and generation of figures. In addition, Rafael Davalos acknowledges the NSF CAREER (CBET 1055913) and the Virginia Tech Institute for Critical Technologies and Applied Sciences (ICTAS) for support of the modeling effort described in the manuscript, and Mark Ortiz acknowledges Dr. Edward Lee of UCLA Radiology for providing SEM images and H&E histopathology information.

References

  1. 1.
    Al-Sakere B, et al. Tumor ablation with irreversible electroporation. PLoS ONE. 2007;2(11):e1135.PubMedCrossRefGoogle Scholar
  2. 2.
    Davalos RV, Mir LM, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng. 2005;33(2):223–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Edd JF, et al. In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Trans Biomed Eng. 2006;53(7):1409–15.PubMedCrossRefGoogle Scholar
  4. 4.
    Mir LM. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry. 2001;53(1):1–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Andre F, Mir LM. DNA electrotransfer: its principles and an updated review of its therapeutic applications. Gene Ther. 2004;11 Suppl 1:S33–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Mir LM, et al. Electric pulse-mediated gene delivery to various animal tissues. Adv Genet. 2005;54:83–114.PubMedCrossRefGoogle Scholar
  7. 7.
    Lee RC, Zhang D, Hannig J. Biophysical injury mechanisms in electrical shock trauma. In: Yarmish ML, Diller KR, Toner M, editors. Annual review of biomedical engineering. Palo Alto: Annual Review Press; 2000. p. 477–509.Google Scholar
  8. 8.
    Weaver JC. Electroporation of cells and tissues. IEEE Trans Plasma Sci. 2000;28(1):24–33.CrossRefGoogle Scholar
  9. 9.
    Sale AJ, Hamilton WA. Effects of high electric fields on micro-organisms. 1. Killing of bacteria and yeasts. Biochim Biophys Acta. 1967;148:781–8.CrossRefGoogle Scholar
  10. 10.
    Neu JC, Krassowska W. Asymptotic model of electroporation. Phys Rev E. 1999;59(3):3471–82.CrossRefGoogle Scholar
  11. 11.
    Abidor IG, et al. Electric breakdown of bilayer lipid-membranes. 1. Main experimental facts and their qualitative discussion. Bioelectrochem Bioenerg. 1979;6(1):37–52.CrossRefGoogle Scholar
  12. 12.
    Glaser RW, et al. Reversible electrical breakdown of lipid bilayers—formation and evolution of pores. Biochim Biophys Acta. 1988;940(2):275–87.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee EW, et al. Electron microscopic (EM) demonstration and evaluation of irreversible electroporation (IRE)-induced nanopores on hepatocyte membranes. In SIR Annual Meeting Poster Presentation, Chicago, IL; 2011.Google Scholar
  14. 14.
    Gowrishankar TR, Weaver JC. An approach to electrical modeling of single and multiple cells. Proc Natl Acad Sci USA. 2003;100(6):3203–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Davalos RV, Otten DM, Rubinsky B. A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine. IEEE Trans Biomed Eng. 2002;49(4):400–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Pavlin M, Miklavcic D. Effective conductivity of a suspension of permeabilized cells: a theoretical analysis. Biophys J. 2003;85:719–29.PubMedCrossRefGoogle Scholar
  17. 17.
    Gehl J, et al. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys Acta. 1999;1428(2–3):223–40.Google Scholar
  18. 18.
    Onik G, Mikus P, Rubinsky B. Irreversible electroporation: implications for prostate ablation. Technol Cancer Res Treat. 2007;6(4):295–300.PubMedGoogle Scholar
  19. 19.
    Rubinsky B, Onik G, Mikus P. Irreversible electroporation: a new ablation modality–clinical implications. Technol Cancer Res Treat. 2007;6(1):37–48.PubMedGoogle Scholar
  20. 20.
    Gervais DA, et al. Radiofrequency ablation of renal cell carcinoma: part 2, Lessons learned with ablation of 100 tumors. Am J Roentgenol. 2005;185(1):72–80.CrossRefGoogle Scholar
  21. 21.
    MacMahon PJ, et al. Modified prostate volume algorithm improves transrectal US volume estimation in men presenting for prostate brachytherapy. Radiology. 2009;250(1):273–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Pennes HH. Analysis of tissue and arterial blood ­temperatures in the resting forearm. J Appl Physiol. 1948;1:93–122.PubMedGoogle Scholar
  23. 23.
    Davalos RV, Rubinsky B, Mir LM. Theoretical analysis of the thermal effects during in vivo tissue electroporation. Bioelectrochemistry. 2003;61(1–2):99–107.PubMedCrossRefGoogle Scholar
  24. 24.
    Becker SM, Kuznetsov AV. Numerical modeling of in vivo plate electroporation thermal dose assessment. J Biomech Eng. 2006;128(1):76–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Duck FA. Physical properties of tissues: a comprehensive reference book. San Diego: Academic Press; 1990.Google Scholar
  26. 26.
    Davalos RV, et al. Electrical impedance tomography for imaging tissue electroporation. IEEE Trans Biomed Eng. 2004;51(5):761–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Bhatt DL, Gaylor DC, Lee RC. Rhabdomyolysis due to pulses electric fields. Plast Reconstr Surg. 1990;86(1):1–11.PubMedCrossRefGoogle Scholar
  28. 28.
    Miklavcic D, et al. Sequential finite element model of tissue electropermeabilisation. In Proceedings of the 26th Annual International Conference of the IEEE EMBS, San Francisco, CA; 2004.Google Scholar
  29. 29.
    Sel D, Lebar AM, Miklavcic D. Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization. IEEE Trans Biomed Eng. 2007;54(5):773–81.PubMedCrossRefGoogle Scholar
  30. 30.
    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. 2000;1523:73–83.PubMedCrossRefGoogle Scholar
  31. 31.
    Sel D, et al. Sequential finite element model of tissue electropermeabilization. IEEE Trans Biomed Eng. 2005;52(5):816–27.PubMedCrossRefGoogle Scholar
  32. 32.
    Lee RC, Despa F. Distinguishing electroporation from thermal injuries in electrical shock by MR imaging. In: Engineering in medicine and biology, 27th Annual Conference. Shanghai, China: IEEE; 2005.Google Scholar
  33. 33.
    Tropea BI, Lee RC. Thermal injury kinetics in electrical trauma. J Biomech Eng. 1992;114:241–50.PubMedCrossRefGoogle Scholar
  34. 34.
    Henriques FC, Moritz AR. Studies in thermal injuries: the predictability and the significance of thermally induced rate processes leading to irreversible epidermal damage. Arch Pathol. 1947;43:489–502.Google Scholar
  35. 35.
    Diller KR. Modeling of bioheat transfer processes at high and low temperatures. In: Choi YI, editor. Bioengineering heat transfer. Boston: Academic Press; 1992. p. 157–357.CrossRefGoogle Scholar
  36. 36.
    Rylander MN, et al. Optimizing HSP expression in prostate cancer laser therapy through predictive ­computational models. J Biomed Opt. 2005;11(4):04111131–16.Google Scholar
  37. 37.
    Diller KR, Hayes LJ. A finite-element model of burn injury in blood-perfused skin. J Biomech Eng Trans Asme. 1983;105(3):300–7.CrossRefGoogle Scholar
  38. 38.
    Garcia PA, et al. Intracranial nonthermal irreversible electroporation: in vivo analysis. J Membr Biol. 2010;236(1):127–36.PubMedCrossRefGoogle Scholar
  39. 39.
    Duck FA. Physical properties of tissue: a comprehensive reference book. New York: Academic Press; 1990.Google Scholar
  40. 40.
    Tracy CR, Kabbani W, Cadeddu JA. Irreversible electroporation (IRE): a novel method for renal tissue ablation. BJU Int. 2011;107(12):1982–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Charpentier KP. Irreversible electroporation of the liver and liver hilum in swine. In Society of Surgical Oncology Annual Meeting, San Antonio; 2011.Google Scholar
  42. 42.
    Lee EW, Loh CT, Kee ST. Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol Cancer Res Treat. 2007;6(4):287–94.PubMedGoogle Scholar
  43. 43.
    Anderson JK, et al. Time course of nicotinamide adenine dinucleotide diaphorase staining after renal radiofrequency ablation influences viability assessment. J Endourol. 2007;21(2):223–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Rubinsky B. Irreversible electroporation in medicine. Technol Cancer Res Treat. 2007;6(4):255–60.PubMedGoogle Scholar
  45. 45.
    Neal 2nd RE, et al. Successful treatment of a large soft tissue sarcoma with irreversible electroporation. J Clin Oncol. 2011;29:372–7.CrossRefGoogle Scholar
  46. 46.
    Garcia PA, et al. Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol Cancer Res Treat. 2011;10(1):73–83.PubMedGoogle Scholar
  47. 47.
    Ellis TL, et al. Nonthermal irreversible electroporation for intracranial surgical applications. J Neurosurg. 2011;114:681–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Oncology/Surgery DivisionAngioDynamics, Inc.FremontUSA
  2. 2.Department of Biomedical Engineering and SciencesVirginia Tech–Wake Forest UniversityBlacksburgUSA

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