Analysis of tissue heating during electroporation based therapy: A 3D FEM model for a pair of needle electrodes

Abstract

Cancer electrochemotherapy and electro gene therapy are emerging methods in molecular medicine. Both are based on electroporation mediated introduction of foreign molecules (drugs, DNA) into target cells. Depending on the application (electrochemotherapy or DNA electrotransfer), pulse delivery protocols and electrode geometry are chosen to achieve above the permeabilization threshold electric field in the target tissue volume. In this study we present the analysis of tissue heating as a potential side effect of strong electric pulses. The analysis is based on a 3D finite-element model of tissue in which a pair of needle electrodes was inserted. By setting the appropriate boundary conditions, we simulated driving of electrodes with short, high voltage, electropermeabilizing pulses and with longer, lower voltage, electrophoretic pulses. Time dependent solutions for electric field and temperature distribution were obtained by FEM solver. The results show localized tissue heating near the electrodes. This is predominately due to the sharp radial decrease of the electric field around the needles. For a given electrode geometry, the extent of thermal effects strongly depends on tissue electrical conductivity and parameters of electric pulses (number of pulses, pulse amplitude and duration). When comparing a pair of needles to parallel plate electrodes, the results show, that with needle electrodes, it is harder to avoid tissue heating and to achieve, in a larger tissue volume, local electric field between reversible and irreversible permeabilization threshold. The results of this numerical study are in agreement with previous in vivo experiments.