Mathematical modeling of the thermal effects of irreversible electroporation for in vitro, in vivo, and clinical use: a systematic review

Irreversible electroporation (IRE) is a relatively new ablation method for the treatment of unresectable cancers. Although the main mechanism of IRE is electric permeabilization of cell membranes, the question is to what extent thermal effects of IRE contribute to tissue ablation. This systematic review reviews the mathematical models used to numerically simulate the heat-generating effects of IRE, and uses the obtained data to assess the degree of mild-hyperthermic (temperatures between 40 °C and 50 °C) and thermally ablative (TA) effects (temperatures exceeding 50 °C) caused by IRE within the IRE-treated region (IRE-TR). A systematic search was performed in medical and technical databases for original studies reporting on numerical simulations of IRE. Data on used equations, study design, tissue models, maximum temperature increase, and surface areas of IRE-TR, mild-hyperthermic, and ablative temperatures were extracted. Several identified models, including Laplace equation for calculation of electric field distribution, Pennes Bioheat Equation for heat transfer, and Arrhenius model for thermal damage, were applied on various electrode and tissue models. Median duration of combined mild-hyperthermic and TA effects is 20% of the treatment time. Based on the included studies, mild-hyperthermic temperatures occurred in 30% and temperatures ≥50 °C in 5% of the IRE-TR. Simulation results in this review show that significant mild-hyperthermic effects occur in a large part of the IRE-TR, and direct thermal ablation in comparatively small regions. Future studies should aim to optimize clinical IRE protocols, maintaining a maximum irreversible permeabilized region with minimal TA effects.

不可逆电穿孔（IRE）是一种针对不可切除癌症的新型消融治疗手段。尽管IRE的主要机制是细胞膜的电渗透，但问题的关键在于IRE的热效应在多大程度上有助于组织消融。本系统综述回顾了用于数值模拟IRE热生成效应的数学模型，并利用所得数据评估IRE治疗区域内（IRE-TR）由IRE引起的轻度过热（40°C至50°C之间）和热消融（温度超过50°C）的程度。在医学和技术数据库中进行了系统搜索，以寻找关于IRE数值模拟的原研究报告。提取了使用方程、研究设计、组织模型、最大温升以及IRE-TR、轻度过热和消融温度的表面积等相关数据。包括用于计算电场分布的拉普拉斯方程、用于传热的彭斯生物热方程和用于热损伤的阿伦尼乌斯模型在内的几个识别出的模型，被应用于各种电极和组织模型上。轻度过热和热消融效果的均值持续时间占治疗时间的20%。基于纳入的研究，IRE-TR中有30%发生轻度过热，5%的温度≥50°C。本综述中的模拟结果表明，在IRE-TR的大部分区域发生显著的轻度过热效应，而在相对较小的区域发生直接热消融。未来的研究应致力于优化临床IRE方案，在保持最大不可逆渗透区域的同时，将热消融效应降至最低。