Perera-Bel Enric, Mercadal Borja, Garcia-Sanchez Tomas, Gonzalez Ballester Miguel Angel, Ivorra Antoni
IEEE Trans Biomed Eng. 2022 Apr;69(4):1318-1327. doi: 10.1109/TBME.2021.3115029. Epub 2022 Mar 18.
Irreversible electroporation (IRE) is a non-thermal tissue ablation therapy which is induced by applying high voltage waveforms across electrode pairs. When multiple electrode pairs are sequentially used, the treatment volume (TV) is typically computed as the geometric union of the TVs of individual pairs. However, this method neglects that some regions are exposed to overlapping treatments. Recently, a model describing cell survival probability was introduced which effectively predicted TV with overlapping fields in vivo. However, treatment overlap has yet to be quantified. This study characterizes TV overlap in a controlled in vitro setup with the two existing methods which are compared to an adapted logistic model proposed here.
CHO cells were immobilized in agarose gel. Initially, we characterized the electric field threshold and the cell survival probability for overlapping treatments. Subsequently, we created a 2D setup where we compared and validated the accuracy of the different methods in predicting the TV.
Overlap can reduce the electric field threshold required to induce cell death, particularly for treatments with low pulse number. However, it does not have a major impact on TV in the models assayed here, and all the studied methods predict TV with similar accuracy.
Treatment overlap has a minor influence in the TV for typical protocols found in IRE therapies.
This study provides evidence that the modeling method used in most pre-clinical and clinical studies seems adequate.
不可逆电穿孔（IRE）是一种非热组织消融疗法，通过在电极对之间施加高压波形来诱导。当依次使用多个电极对时，治疗体积（TV）通常计算为各个电极对的TV的几何并集。然而，这种方法忽略了一些区域会受到重叠治疗的影响。最近，引入了一种描述细胞存活概率的模型，该模型有效地预测了体内重叠场的TV。然而，治疗重叠尚未得到量化。本研究在可控的体外设置中，用两种现有方法对TV重叠进行了表征，并将其与本文提出的一种改进的逻辑模型进行比较。
将CHO细胞固定在琼脂糖凝胶中。首先，我们表征了重叠治疗的电场阈值和细胞存活概率。随后，我们创建了一个二维设置，在其中比较并验证了不同方法预测TV的准确性。
重叠可以降低诱导细胞死亡所需的电场阈值，特别是对于低脉冲数的治疗。然而，它对本文所分析模型中的TV没有重大影响，并且所有研究方法预测TV的准确性相似。
治疗重叠对IRE疗法中典型方案的TV影响较小。
本研究提供了证据，表明大多数临床前和临床研究中使用的建模方法似乎是足够的。
