Determination of the critical electric field strength for therapeutic irreversible electroporation by using a three-dimensional cell culture model

Abstract

Irreversible electroporation (IRE) is a less-invasive therapy to treat tumors by delivering short and intensive electric pulses to the tissue. The pulse settings are important factors that affect IRE outcome. In this study, we proposed a three-dimensional (3-D) cell culture model to determine the critical electric field for IRE depending on the effect of pulse parameters, particularly pulse repetition and interval, and adjuvants. Agarose gel containing fibroblasts was used as a tissue phantom. After application of electric pulses, the area that contained full of necrotized cells was quantified and compared with the distribution of the electric field estimated from a numerical analysis, so that the critical electric field strength to cause cell necrosis was determined. Ablated area increased as a function of pulse repetition, and reached a plateau at 120 pulses. When the pulse interval was extended from 100 ms to 1 s, the ablated area increased by approximately 30%. Addition of 10% DMSO and 5% ethanol also significantly increased the ablated area by 15% and 55%, respectively, indicating a reduction of the critical electric field strength. The critical electric field strength was independent of the magnitude of the applied voltage when the pulse length, interval, and the number of pulses were fixed. A longer interval and adjuvants increased the ablated area, and therefore decreased the critical electric field strength. The 3-D tissue phantom composed of agarose gel and cells was useful for examination of the IRE effect by comparing the experimentally determined necrotized region with a numerical analysis.