In Vivo Results of a New Focal Tissue Ablation Technique: Irreversible Electroporation

TLDR

Electroporation generates electric‑potential‑induced nanoscale defects in cell membranes, and irreversible electroporation permanently disrupts these defects to kill cells. This study demonstrates that irreversible electroporation can serve as an effective, drug‑free, nonthermal tissue ablation technique. The authors tested this by delivering a single 20‑ms, 1000 V/cm square pulse to the livers of male Sprague‑Dawley rats, as predicted to produce nonthermal IRE. The pulse produced microvascular occlusion, endothelial necrosis, ischemic parenchymal damage with preserved large vessels, hepatocyte degeneration, and nonthermal injury with sharp borders at 300–500 V/cm.

Abstract

This paper reports results of in vivo experiments that confirm the feasibility of a new minimally invasive method for tissue ablation, irreversible electroporation (IRE). Electroporation is the generation of a destabilizing electric potential across biological membranes that causes the formation of nanoscale defects in the lipid bilayer. In IRE, these defects are permanent and lead to cell death. This paper builds on our earlier theoretical work and demonstrates that IRE can become an effective method for nonthermal tissue ablation requiring no drugs. To test the capability of IRE pulses to ablate tissue in a controlled fashion, we subjected the livers of male Sprague-Dawley rats to a single 20-ms-long square pulse of 1000 V/cm, which calculations had predicted would cause nonthermal IRE. Three hours after the pulse, treated areas in perfusion-fixed livers exhibited microvascular occlusion, endothelial cell necrosis, and diapedeses, resulting in ischemic damage to parenchyma and massive pooling of erythrocytes in sinusoids. However, large blood vessel architecture was preserved. Hepatocytes displayed blurred cell borders, pale eosinophilic cytoplasm, variable pyknosis and vacuolar degeneration. Mathematical analysis indicates that this damage was primarily nonthermal in nature and that sharp borders between affected and unaffected regions corresponded to electric fields of 300-500 V/cm.