Annals of Biomedical Engineering

, Volume 42, Issue 3, pp 475–487

In Vitro and Numerical Support for Combinatorial Irreversible Electroporation and Electrochemotherapy Glioma Treatment

Authors

    • Bioelectromechanical Systems LabVirginia Tech – Wake Forest School of Biomedical Engineering and Sciences
    • Radiology Research UnitThe Alfred Hospital
  • J. H. RossmeislJr.
    • Neurology/Neurosurgery Service and Center for Comparative OncologyVA-MD Regional College of Veterinary Medicine
  • V. D’Alfonso
    • Neurology/Neurosurgery Service and Center for Comparative OncologyVA-MD Regional College of Veterinary Medicine
  • J. L. Robertson
    • Cancer Engineering GroupVirginia Tech – Wake Forest School of Biomedical Engineering and Sciences
  • P. A. Garcia
    • Bioelectromechanical Systems LabVirginia Tech – Wake Forest School of Biomedical Engineering and Sciences
  • S. Elankumaran
    • Department of Biomedical Sciences and PathobiologyVA-MD Regional College of Veterinary Medicine
  • R. V. Davalos
    • Bioelectromechanical Systems LabVirginia Tech – Wake Forest School of Biomedical Engineering and Sciences
Article

DOI: 10.1007/s10439-013-0923-2

Cite this article as:
Neal, R.E., Rossmeisl, J.H., D’Alfonso, V. et al. Ann Biomed Eng (2014) 42: 475. doi:10.1007/s10439-013-0923-2

Abstract

Irreversible electroporation (IRE) achieves targeted volume non-thermal focal ablation using a series of brief electric pulses to kill cells by disrupting membrane integrity. Electrochemotherapy (ECT) uses lower numbers of sub-lethal electric pulses to disrupt membranes for improved drug uptake. Malignant glioma (MG) brain tumors are difficult to treat due to diffuse peripheral margins into healthy neural tissue. Here, in vitro experimental data and numerical simulations investigate the feasibility for IRE-relevant pulse protocols with adjuvant ECT drugs to enhance MG treatment. Cytotoxicity curves were produced on two glioma cell lines in vitro at multiple pulse strengths and drug doses with Bleomycin or Carboplatin. Pulses alone increased cytotoxicity with higher pulse numbers and strengths, reaching >90% by 800 V/cm with 90 pulses. Chemotherapeutic addition increased cytotoxicity by >50% for 1 ng/mL concentrations of either drug relative to 80 pulses alone with J3T cells at electric fields ≥400 V/cm. In addition to necrosis, transmission electron microscopy visualizes apoptotic morphological changes and Hoescht 33342 staining shows apoptotic cell fractions varying with electric field and drug dose relative to controls. Numerically simulated treatment volumes in a canine brain show IRE combined with ECT expands therapeutic volume by 2.1–3.2 times compared to IRE alone.

Keywords

Combined therapyNon-thermal focal ablationBrain cancerIREECTNumerical modelingMinimally invasive surgeryMultimodality oncologyTargeted therapy

Abbreviations

IRE

Irreversible electroporation

ECT

Electrochemotherapy

BBB

Blood–brain-barrier

Copyright information

© Biomedical Engineering Society 2013