Preclinical Studies on Irreversible Electroporation

Abstract

Irreversible electroporation (IRE) employs a series of brief electric pulses to destabilize cell membranes by altering the transmembrane voltage to create nanoscale defects that induce cell death. Its nonthermal mechanism makes it an ideal treatment modality for treatment of tumors near critical structures and vasculature, which are contraindications for other thermal ablation modalities. Since its conception, IRE has been investigated for applications in several organs to determine its safety and efficacy. IRE ablation zones, thermal effects, potential for real-time imaging, and cell death mechanism have been thoroughly investigated in vivo, leading to its successful transition to the clinical environment. This chapter describes IRE findings in the preclinical setting, with a focus on the pancreas, kidney, liver, bone, brain, prostate, and lung, and general implications with respect to successful therapy outcomes. These include consistency of ablation zones with different treatment parameters, histology of ablation zones showing tissue and tumor destruction, in vivo safety during and after treatment, and efficacy in terms of tumor regression. In addition, the patency of critical structures such as blood vessels, nerves, and ductal systems is briefly discussed. Newer preclinical findings such as immune response activation, adjuvant therapies, and modulating pulse regimes to improve treatment outcome and ease treatment delivery are outlined.