The Enlargement of Ablation Area by Electrolytic Irreversible Electroporation (E-IRE) Using Pulsed Field with Bias DC Field

Abstract

Irreversible electroporation (IRE) by high-strength electric pulses is a biomedical technique that has been effectively used for minimally invasive tumor therapy while maintaining the functionality of adjacent important tissues, such as blood vessels and nerves. In general, pulse delivery using needle electrodes can create a reversible electroporation region beyond both the ablation area and the vicinity of the needle electrodes, limiting enlargement of the ablation area. Electrochemical therapy (EChT) can also be used to ablate a tumor near electrodes by electrolysis using a direct field with a constant current or voltage (DC field). Recently, reversible electroporated cells have been shown to be susceptible to electrolysis at relatively low doses. Reversible electroporation can also be combined with electrolysis for tissue ablation. Therefore, the objective of this study is to use electrolysis to remove the reversible electroporation area and thereby enlarge the ablation area in potato slices in vitro using a pulsed field with a bias DC field (constant voltage). We call this protocol electrolytic irreversible electroporation (E-IRE). The area over which the electrolytic effect induced a pH change was also measured. The results show that decreasing the pulse frequency using IRE alone is found to enlarge the ablation area. The ablation area generated by E-IRE is significantly larger than that generated by using IRE or EChT alone. The ablation area generated by E-IRE at 1 Hz is 109.5% larger than that generated by IRE, showing that the reversible electroporation region is transformed into an ablation region by electrolysis. The area with a pH change produced by E-IRE is larger than that produced by EChT alone. Decreasing the pulse frequency in the E-IRE protocol can further enlarge the ablation area. The results of this study are a preliminary indication that the E-IRE protocol can effectively enlarge the ablation area and enhance the efficacy of traditional IRE for use in ablating large tumors.

Keywords: Electrolytic irreversible electroporation; Pulse frequency; Reversible electroporation; Tumor treatment.