Influence of anisotropic tissue electrical conductivity on electric field and temperature distribution during electroporation-based therapy

Abstract

Electroporation is a biophysical phenomenon caused by externally applied high-intensity electric field to cells that results in the increase of membrane conductivity and permeability. Among many applications it is used for in vivo drug delivery to tumors (electrochemotherapy) and for nonviral delivery of foreign genes into various tissues (gene electrotransfer). Since high-intensity electric field is applied and strong current passes through tissue, it can produce heating (Joule effect) which can cause tissue thermal damage. In our study we evaluated electric field and temperature distribution during typical electrochemotherapy pulsing protocol and gene electrotransfer specific protocol in tissue with anisotropic electrical conductivity (e.g. skeletal muscle). We developed a coupled electrical-thermal model and used finite-element method to solve it for a pair of needle electrodes 0.7 mm in diameter, 8 mm apart. The results show markedly different electric field and temperature distribution if electrode axis (defined by the line connecting two needle electrodes) is positioned along muscle fibres (i.e. longitudinally, in parallel) when compared to the position when electrode axis is across muscle fibers (i.e. transversally, perpendicularly). If electrodes are applied in the direction where electrode axis is along muscle fibers, tissue heating is higher than in the case when electrodes are applied across muscle fibers. For the two examined pulse protocols and skeletal muscle as a target tissue, temperature increase due to electric pulses was within physiological range ( < 43 °C) except near the needle tip. Increase of pulse amplitude, duration or number of pulses might induce thermal damage which is more likely to occur in gene electrotransfer protocol specially if electrode axis is oriented along muscle fibers.