Nonthermal Irreversible Electroporation as a Focal Ablation Treatment for Brain Cancer

  • Paulo A. Garcia
  • John H. RossmeislJr.
  • Thomas L. Ellis
  • Rafael V. Davalos
Part of the Tumors of the Central Nervous System book series (TCNS, volume 12)


Irreversible Electroporation (IRE) is a new focal tissue ablation technique that has shown great promise as a treatment for a variety of soft-tissue neoplasms. The therapy uses pulsed electric fields to destabilize cell membranes and achieve tissue death in a non-thermal manner. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about 1 min. In this chapter we describe the first systematic in vivo studies of IRE in canine brain tissue. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically in normal dogs. The necrotic lesions created with IRE were sub-millimeter in resolution, sharply delineated from normal brain, and spared the major blood vessels. In addition, our preliminary results in a rodent study indicate that IRE transiently disrupts the BBB adjacent to the ablated area in a voltage-dependent manner with implications for enhanced delivery of cytotoxic agents to regions with infiltrative tumor cells. Finally, we present representative case examples demonstrating therapeutic planning aspects, clinical applications, and results of IRE ablation of spontaneous malignant intracranial gliomas in canine patients. Our group has demonstrated that IRE ablation can be performed safely, and is effective at reducing the tumor volume and associated intracranial hypertension, and allows for improvement in tumor-associated neurologic dysfunction. Our work illustrates the potential benefits of IRE for in vivo ablation of neoplastic brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal.


Malignant Glioma Pulse Electric Field Electric Field Distribution Major Blood Vessel Irreversible Electroporation 
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.



The work highlighted in this chapter was supported by the Coulter Foundation, the Golfer’s Against Cancer, and by the CBET-0933335 and CAREER CBET-1055913 awards from the National Science Foundation (NSF) in the United States of America. The authors would also like to thank AngioDynamics® Inc. for loan of their equipment and for technical support of these studies.


  1. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN (2011) Principles of and advances in percutaneous ablation. Radiology 258(2):351–369PubMedCrossRefGoogle Scholar
  2. Al-Sakere B, Andre F, Bernat C, Connault E, Opolon P, Davalos RV, Rubinsky B, Mir LM (2007) Tumor ablation with irreversible electroporation. PLoS One 2(11):e1135PubMedCentralPubMedCrossRefGoogle Scholar
  3. Appelbaum L, Ben-David E, Sosna J, Nissenbaum Y, Goldberg SN (2012) Us findings after irreversible electroporation ablation: radiologic-pathologic correlation. Radiology 262(1):117–125PubMedCrossRefGoogle Scholar
  4. Atsumi H, Matsumae M, Kaneda M, Muro I, Mamata Y, Komiya T, Tsugu A, Tsugane R (2001) Novel laser system and laser irradiation method reduced the risk of carbonization during laser interstitial thermotherapy: assessed by MR temperature measurement. Lasers Surg Med 29(2):108–117PubMedCrossRefGoogle Scholar
  5. Ball C, Thomson KR, Kavnoudias H (2010) Irreversible electroporation: a new challenge in “out of operating theater” anesthesia. Anesth Analg 110(5):1305–1309PubMedCrossRefGoogle Scholar
  6. Ben-David E, Appelbaum L, Sosna J, Nissenbaum I, Goldberg SN (2012) Characterization of irreversible electroporation ablation in in vivo porcine liver. Am J Roentgenol 198(1):W62–W68CrossRefGoogle Scholar
  7. Cosman ER, Nashold BS, Bedenbaugh P (1983) Stereotactic radiofrequency lesion making. Appl Neurophysiol 46(1–4):160–166PubMedGoogle Scholar
  8. Davalos RV, Mir LM, Rubinsky B (2005) Tissue ablation with irreversible electroporation. Ann Biomed Eng 33(2):223–231PubMedCrossRefGoogle Scholar
  9. Dickinson PJ, Roberts BN, Higgins RJ, Leutenegger CM, Bollen AW, Kass PH, LeCouteur RA (2006) Expression of receptor tyrosine kinases vegfr-1 (flt-1), vegfr-2 (kdr), egfr-1, pdgfra and c-met in canine primary brain tumours. Vet Comp Oncol 4(3):132–140PubMedCrossRefGoogle Scholar
  10. Edd JF, Davalos RV (2007) Mathematical modeling of irreversible electroporation for treatment planning. Technol Cancer Res Treat 6:275–286PubMedCrossRefGoogle Scholar
  11. Ellis TL, Garcia PA, Rossmeisl JH Jr, Henao-Guerrero N, Robertson J, Davalos RV (2011) Nonthermal irreversible electroporation for intracranial surgical applications. Laboratory investigation. J Neurosurg 114(3):681–688PubMedCrossRefGoogle Scholar
  12. Garcia PA, Pancotto T, Rossmeisl JH, Henao-Guerrero N, Gustafson NR, Daniel GB, Robertson JL, Ellis TL, Davalos RV (2011a) Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol Cancer Res Treat 10(1):73–83PubMedGoogle Scholar
  13. Garcia PA, Rossmeisl JH Jr, Neal RE 2nd, Ellis TL, Davalos RV (2011b) A parametric study delineating irreversible electroporation from thermal damage based on a minimally invasive intracranial procedure. Biomed Eng Online 10(1):34PubMedCentralPubMedCrossRefGoogle Scholar
  14. Garcia PA, Rossmeisl JH, Neal RE II, Ellis TL, Olson J, Henao-Guerrero N, Robertson J, Davalos RV (2010) Intracranial nonthermal irreversible electroporation: in vivo analysis. J Membr Biol 236(1):127–136PubMedCrossRefGoogle Scholar
  15. Garcia PA, Rossmeisl JH Jr, Robertson JL, Olson JD, Johnson AJ, Ellis TL, Davalos RV (2012) 7.0-T Magnetic resonance imaging characterization of acute blood–brain-barrier disruption achieved with intracranial irreversible electroporation. PLoS ONE 7(11):e50482PubMedCentralPubMedCrossRefGoogle Scholar
  16. Heidner GL, Kornegay JN, Page RL, Dodge RK, Thrall DE (1991) Analysis of survival in a retrospective study of 86 dogs with brain tumors. J Vet Intern Med 5(4):219–226PubMedCrossRefGoogle Scholar
  17. Ivorra A, Al-Sakere B, Rubinsky B, Mir LM (2009) In vivo electrical conductivity measurements during and after tumor electroporation: conductivity changes reflect the treatment outcome. Phys Med Biol 54(19):5949–5963PubMedCrossRefGoogle Scholar
  18. La Rocca RV, Mehdorn HM (2009) Localized BCNU chemotherapy and the multimodal management of malignant glioma. Curr Med Res Opin 25(1):149–160PubMedCrossRefGoogle Scholar
  19. Lee EW, Loh CT, Kee ST (2007) Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol Cancer Res Treat 6(4):287–294PubMedCrossRefGoogle Scholar
  20. Miklavcic D, Semrov D, Mekid H, Mir LM (2000) A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim Biophys Acta 1523(1):73–83PubMedCrossRefGoogle Scholar
  21. Neal R II, Garcia P, Robertson J, Davalos R (2012) Experimental characterization and numerical modeling of tissue electrical conductivity during pulsed electric fields for irreversible electroporation treatment planning. IEEE Trans Biomed Eng 99:1Google Scholar
  22. Neal RE II, Rossmeisl J, Garcia PA, Lanz O, Henao- Guerrero N, Davalos RV (2011) A case report on the successful treatment of a large soft-tissue sarcoma with irreversible electroporation. J Clin Oncol 29:1–6CrossRefGoogle Scholar
  23. Onik G, Mikus P, Rubinsky B (2007) Irreversible electroporation: implications for prostate ablation. Technol Cancer Res Treat 6(4):295–300PubMedCrossRefGoogle Scholar
  24. Rossmeisl JH, Duncan RB, Huckle WR, Troy GC (2007) Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms. Am J Vet Res 68(11):1239–1245PubMedCrossRefGoogle Scholar
  25. Rubinsky B, Onik G, Mikus P (2007) Irreversible electroporation: a new ablation modality–clinical implications. Technol Cancer Res Treat 6(1):37–48PubMedCrossRefGoogle Scholar
  26. Schmidt CR, Shires P, Mootoo M (2012) Real-time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis. HPB 14(2):98–102PubMedCentralPubMedCrossRefGoogle Scholar
  27. Stoica G, Kim HT, Hall DG, Coates JR (2004) Morphology, immunohistochemistry, and genetic alterations in dog astrocytomas. Vet Pathol 41(1):10–19PubMedCrossRefGoogle Scholar
  28. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRefGoogle Scholar
  29. Tacke J (2001) Thermal therapies in interventional mr imaging Cryotherapy. Neuroimaging Clin N Am 11(4):759–765PubMedGoogle Scholar
  30. Thomson KR, Cheung W, Ellis SJ, Federman D, Kavnoudias H, Loader-Oliver D, Roberts S, Evans P, Ball C, Haydon A (2011) Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol 22(5):611–621PubMedCrossRefGoogle Scholar
  31. Young BD, Levine JM, Porter BF, Chen-Allen AV, Rossmeisl JH, Platt SR, Kent M, Fosgate GT, Schatzberg SJ (2011) Magnetic resonance imaging features of intracranial astrocytomas and oligodendrogliomas in dogs. Vet Radiol Ultrasound 52(2):132–141PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Paulo A. Garcia
    • 1
  • John H. RossmeislJr.
    • 2
  • Thomas L. Ellis
    • 3
  • Rafael V. Davalos
    • 4
  1. 1.School of Biomedical Engineering and SciencesVirginia Tech – Wake Forest UniversityBlacksburgUSA
  2. 2.Department of Small Animal Clinical SciencesVirginia-Maryland Regional College of Veterinary MedicineBlacksburgUSA
  3. 3.Department of NeurosurgeryWake Forest University School of MedicineWinston-SalemUSA
  4. 4.School of Biomedical Engineering and SciencesVirginia Tech – Wake Forest UniversityeBlacksburgUSA

Personalised recommendations