The Journal of Membrane Biology

, Volume 236, Issue 1, pp 127–136 | Cite as

Intracranial Nonthermal Irreversible Electroporation: In Vivo Analysis

  • Paulo A. Garcia
  • John H. RossmeislJr.
  • Robert E. NealII
  • Thomas L. Ellis
  • John D. Olson
  • Natalia Henao-Guerrero
  • John Robertson
  • Rafael V. Davalos
Article

Abstract

Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive technique to treat cancer. It is unique because of its nonthermal mechanism of tumor ablation. Intracranial NTIRE procedures involve placing electrodes into the targeted area of the brain and delivering a series of short but intense electric pulses. The electric pulses induce irreversible structural changes in cell membranes, leading to cell death. We correlated NTIRE lesion volumes in normal brain tissue with electric field distributions from comprehensive numerical models. The electrical conductivity of brain tissue was extrapolated from the measured in vivo data and the numerical models. Using this, we present results on the electric field threshold necessary to induce NTIRE lesions (495–510 V/cm) in canine brain tissue using 90 50-μs pulses at 4 Hz. Furthermore, this preliminary study provides some of the necessary numerical tools for using NTIRE as a brain cancer treatment. We also computed the electrical conductivity of brain tissue from the in vivo data (0.12–0.30 S/m) and provide guidelines for treatment planning and execution. Knowledge of the dynamic electrical conductivity of the tissue and electric field that correlates to lesion volume is crucial to ensure predictable complete NTIRE treatment while minimizing damage to surrounding healthy tissue.

Keywords

Brain cancer therapy Minimally invasive surgery Nonthermal ablation Tumor ablation Electropermeabilization Bioheat transfer Finite element analysis Electric field correlation Electrical conductivity 

References

  1. Al-Sakere B, Andre F, Bernat C, Connault E, Opolon P, Davalos RV, Rubinsky B, Mir LM (2007a) Tumor ablation with irreversible electroporation. PLoS ONE 11:e1135CrossRefGoogle Scholar
  2. Al-Sakere B, Bernat C, Andre F, Connault E, Opolon P, Davalos RV, Mir LM (2007b) A study of the immunological response to tumor ablation with irreversible electroporation. Technol Cancer Res Treat 6:301–306PubMedGoogle Scholar
  3. Ball C, Thomson KR, Kavnoudias H (2010) Irreversible electroporation: a new challenge in “out of operating theater” anesthesia. Anesth Analg 110:1305–1309CrossRefPubMedGoogle Scholar
  4. Becker SM, Kuznetsov AV (2006) Numerical modeling of in vivo plate electroporation thermal dose assessment. J Biomech Eng 128:76–84CrossRefPubMedGoogle Scholar
  5. Cha S (2009) Neuroimaging in neuro-oncology. Neurotherapeutics 6:465–477CrossRefPubMedGoogle Scholar
  6. Cherubini GB, Mantis P, Martinez TA, Lamb CR, Cappello R (2005) Utility of magnetic resonance imaging for distinguishing neoplastic from non-neoplastic brain lesions in dogs and cats. Vet Radiol Ultrasound 46:384–387CrossRefPubMedGoogle Scholar
  7. Cosman ER Jr, Cosman ER Sr (2005) Electric and thermal field effects in tissue around radiofrequency electrodes. Pain Med 6:405–424CrossRefPubMedGoogle Scholar
  8. Cukjati D, Batiuskaite D, Andre F, Miklavcic D, Mir LM (2007) Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry 70:501–507CrossRefPubMedGoogle Scholar
  9. Davalos RV, Rubinsky B (2004) Electrical impedance tomography of cell viability in tissue with application to cryosurgery. J Biomech Eng 126:305–309CrossRefPubMedGoogle Scholar
  10. Davalos RV, Rubinsky B (2008) Temperature considerations during irreversible electroporation. Int J Heat Mass Transfer 51:5617–5622CrossRefGoogle Scholar
  11. Davalos RV, Rubinsky B, Mir LM (2003) Theoretical analysis of the thermal effects during in vivo tissue electroporation. Bioelectrochemistry 61:99–107CrossRefPubMedGoogle Scholar
  12. Davalos RV, Otten DM, Mir LM, Rubinsky B (2004) Electrical impedance tomography for imaging tissue electroporation. IEEE Trans Biomed Eng 51:761–767CrossRefPubMedGoogle Scholar
  13. Davalos RV, Mir LM, Rubinsky B (2005) Tissue ablation with irreversible electroporation. Ann Biomed Eng 33:223–231CrossRefPubMedGoogle Scholar
  14. Dewhirst MW, Viglianti BL, Lora-Michiels M, Hanson M, Hoopes PJ (2003) Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. Int J Hyperthermia 19:267–294CrossRefPubMedGoogle Scholar
  15. Duck FA (1990) Physical properties of tissues: a comprehensive reference book. Academic Press, San DiegoGoogle Scholar
  16. Edd JF, Davalos RV (2007) Mathematical modeling of irreversible electroporation for treatment planning. Technol Cancer Res Treat 6:275–286PubMedGoogle Scholar
  17. Edd JF, Horowitz L, Davalos RV, Mir LM, Rubinsky B (2006) In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Trans Biomed Eng 53:1409–1415CrossRefPubMedGoogle Scholar
  18. Ellis TL, Garcia PA, Rossmeisl JH, Henao-Guerrero N, Robertson J, Davalos RV (2010) Nonthermal irreversible electroporation for intracranial surgical applications. J Neurosur (in print)Google Scholar
  19. Garcia PA, Rossmeisl JH, Robertson J, Ellis TL, Davalos RV (2009) Pilot study of irreversible electroporation for intracranial surgery. Conf Proc IEEE Eng Med Biol Soc 1:6513–6516Google Scholar
  20. Ivorra A (2010) Tissue electroporation as a biolectric phenomenon: basic concepts. In: Rubinsky B (ed) Irreversible electroporation. Springer, Berlin, pp 23–61CrossRefGoogle Scholar
  21. Ivorra A, Rubinsky B (2007) In vivo electrical impedance measurements during and after electroporation of rat liver. Bioelectrochemistry 70:287–295CrossRefPubMedGoogle Scholar
  22. 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 54:5949–5963CrossRefPubMedGoogle Scholar
  23. Jaffe R (2002) The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging. A task force report of the American Psychiatric Association, 2nd edn. Am J Psychiatry 159:331Google Scholar
  24. Lackovic I, Magjarevic R, Miklavcic D (2009) Three-dimensional finite-element analysis of joule heating in electrochemotherapy and in vivo gene electrotransfer. IEEE Trans Dielec Elec Insul 16:1338–1347CrossRefGoogle Scholar
  25. Latikka J, Kuurne T, Eskola H (2001) Conductivity of living intracranial tissues. Phys Med Biol 46:1611–1616CrossRefPubMedGoogle Scholar
  26. Lee RC, Zhang D, Hannig J (2000) Biophysical injury mechanisms in electrical shock trauma. Annu Rev Biomed Eng 2:477–509CrossRefPubMedGoogle Scholar
  27. Lee EW, Loh CT, Kee ST (2007) Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol Cancer Res Treat 6:287–294PubMedGoogle Scholar
  28. Macek-Lebar A, Miklavcic D (2001) Cell electropermeabilization to small molecules in vitro: control by pulse parameters. Radiol Oncol 35:193–202Google Scholar
  29. Matsumi N, Matsumoto K, Mishima N, Moriyama E, Furuta T, Nishimoto A, Taguchi K (1994) Thermal damage threshold of brain tissue–histological study of heated normal monkey brains. Neurol Med Chir (Tokyo) 34:209–215CrossRefGoogle Scholar
  30. 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 1523:73–83PubMedGoogle Scholar
  31. Mir LM (2001) Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry 53:1–10CrossRefPubMedGoogle Scholar
  32. Neal RE II, Davalos RV (2009) The feasibility of irreversible electroporation for the treatment of breast cancer and other heterogeneous systems. Ann Biomed Eng 37:2615–2625CrossRefPubMedGoogle Scholar
  33. Onik G, Mikus P, Rubinsky B (2007) Irreversible electroporation: implications for prostate ablation. Technol Cancer Res Treat 6:295–300PubMedGoogle Scholar
  34. Pavselj N, Bregar Z, Cukjati D, Batiuskaite D, Mir LM, Miklavcic D (2005) The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals. IEEE Trans Biomed Eng 52:1373–1381CrossRefPubMedGoogle Scholar
  35. Rubinsky B (2007) Irreversible electroporation in medicine. Technol Cancer Res Treat 6:255–260PubMedGoogle Scholar
  36. Rubinsky B, Onik G, Mikus P (2007) Irreversible electroporation: a new ablation modality–clinical implications. Technol Cancer Res Treat 6:37–48PubMedGoogle Scholar
  37. Sapareto SA, Dewey WC (1984) Thermal dose determination in cancer therapy. Int J Radiat Oncol Biol Phys 10:787–800PubMedGoogle Scholar
  38. Sel D, Cukjati D, Batiuskaite D, Slivnik T, Mir LM, Miklavcic D (2005) Sequential finite element model of tissue electropermeabilization. IEEE Trans Biomed Eng 52:816–827CrossRefPubMedGoogle Scholar
  39. Sel D, Lebar AM, Miklavcic D (2007) Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization. IEEE Trans Biomed Eng 54:773–781CrossRefPubMedGoogle Scholar
  40. Thomas WB, Wheeler SJ, Kramer R, Kornegay JN (1996) Magnetic resonance imaging features of primary brain tumors in dogs. Vet Radiol Ultrasound 37:20–27CrossRefGoogle Scholar
  41. Thomson K (2010) Human experience with irreversible electroporation. In: Rubinsky B (ed) Irreversible electroporation. Springer, Berlin, pp 249–254CrossRefGoogle Scholar
  42. Uzuka T, Tanaka R, Takahashi H, Kakinuma K, Matsuda J, Kato K (2001) Planning of hyperthermic treatment for malignant glioma using computer simulation. Int J Hyperthermia 17:114–122CrossRefPubMedGoogle Scholar
  43. Werner J, Buse M (1988) Temperature profiles with respect to inhomogeneity and geometry of the human body. J Appl Physiol 65:1110–1118PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Paulo A. Garcia
    • 1
  • John H. RossmeislJr.
    • 2
  • Robert E. NealII
    • 1
  • Thomas L. Ellis
    • 3
  • John D. Olson
    • 4
  • Natalia Henao-Guerrero
    • 2
  • John Robertson
    • 2
  • Rafael V. Davalos
    • 1
    • 5
  1. 1.Bioelectromechanical Systems (BEMS) Laboratory, School of Biomedical Engineering and Sciences (SBES)Virginia Tech-Wake Forest UniversityBlacksburgUSA
  2. 2.Virginia–Maryland Regional College of Veterinary MedicineBlacksburgUSA
  3. 3.Department of NeurosurgeryWake Forest University School of MedicineWinston-SalemUSA
  4. 4.Center for Biomolecular ImagingWake Forest University School of MedicineWinston-SalemUSA
  5. 5.Bioelectromechanical Systems (BEMS) Laboratory, Department of Engineering Science and Mechanics (ESM)Virginia Polytechnic Institute and State UniversityBlacksburgUSA

Personalised recommendations