Comprehensive review on thermal aspects of nonthermal irreversible electroporation

Irreversible electroporation (IRE) is an innovative cell ablation method based on the concept that the application of excessive electric pulses induces a lethal increase in the permeability of the cell membrane owing to nanoscale defects, resulting in a gentle form of necrotic cell death. Although the mechanism of cell death by IRE is primarily nonthermal, thermal effects are inevitable because electric pulses inherently generate Joule heat. The larger the applied voltage to treat a large target, the greater the Joule heating and the consequent temperature rise. Therefore, the temperature increase due to Joule heating during pulse application should be carefully controlled to minimize thermal damage. Research on IRE is an interdisciplinary endeavor incorporating health science for humanitarian relief and engineering. Therefore, this study provides a comprehensive review of the thermal aspects of IRE based on existing in vitro and in vivo experimental and numerical studies. The paper begins with an overview of IRE treatment covering the geometry and arrangement of electrodes, pulse parameters, and cell death mechanisms, followed by sections on thermal damage evaluation that summarize the significant work of experiments, analysis, and comparisons. Finally, thermal mitigation strategies, including electrode modification, lowering the IRE threshold, and modified pulsing protocols, are discussed.