Implications and considerations of thermal effects when applying irreversible electroporation tissue ablation therapy

Irreversible electroporation (IRE) describes a cellular response to electric field exposure, resulting in the formation of nanoscale defects that can lead to cell death. While this behavior occurs independently of thermally-induced processes, therapeutic ablation of targeted tissues with IRE uses a series of brief electric pulses, whose parameters result in secondary Joule heating of the tissue. Where contemporary clinical pulse protocols use aggressive energy regimes, additional evidence is supplementing original studies that assert care must be taken in clinical ablation protocols to ensure the cumulative thermal effects do not induce damage that will alter outcomes for therapies using the IRE non-thermal cell death process for tissue ablation. In this letter, we seek to clarify the nomenclature regarding IRE as a non-thermal ablation technique, as well as identify existing literature that uses experimental, clinical, and numerical results to discretely address and evaluate the thermal considerations relevant when applying IRE in clinical scenarios, including several approaches for reducing these effects. Existing evidence in the literature describes cell response to electric fields, suggesting cell death from IRE is a unique process, independent from traditional thermal damage. Numerical simulations, as well as preclinical and clinical findings demonstrate the ability to deliver therapeutic IRE ablation without occurrence of morbidity associated with thermal therapies. Clinical IRE therapy generates thermal effects, which may moderate the non-thermal aspects of IRE ablation. Appropriate protocol development, utilization, and pulse delivery devices may be implemented to restrain these effects and maintain IRE as the vastly predominant tissue death modality, reducing therapy-mitigating thermal damage. Clinical applications of IRE should consider thermal effects and employ protocols to ensure safe and effective therapy delivery.