A Multiphysics Model for Studying the Influence of Pulse Repetition Frequency on Tissue Heating During Electrochemotherapy

摘要

For enhancing the delivery of chemotherapeutic drugs to cancer cells or for the delivery of foreign genes, cells can be exposed to strong external electric field, known to induce membrane electroporation. The use of electroporation for delivery of chemotherapy (electrochemotherapy) involves the injection of chemotherapeutic agent followed by a local delivery of a train of short high voltage pulses to the tumor nodule (i.e. 8 square-wave pulses of 100 us delivered at the repetition frequency of 1 Hz, with a voltage-to-distance ratio of up to 1500 V/cm). As biological tissues are conductive, an electrical current is flowing during pulse delivery and Joule heating is also taking place. Recent experimental studies have shown that using higher repetition frequency (e.g. 1 kHz or 5 kHz) have beneficial effects for patients (better tolerance due to a single unpleasant contraction instead of a number of individual contractions, shorter treatment time, etc.). In this work we investigated the influence of pulse repetition frequency on tissue heating. We developed a multiphysics model that couples PDEs for electric and thermal field calculation. Realistic electrode geometries (plate electrodes; needle electrodes) and tissue electrical and thermal properties were used. All simulations were performed with COMSOL Multiphysics. Results of our simulations show that the increase of pulse repetition frequency from 1 Hz to 1 kHz causes higher temperature rise in the tissue due to the Joule heating. However, the increase of bulk tissue temperature is still low and unlikely to induce thermal damage.