A Multiscale Computational Model of Skeletal Muscle Electroporation Validated Using <i>In Situ</i> Porcine Experiments
Rok Šmerc, David A. Ramirez, Samo Mahnič-Kalamiza, Janja Dermol‐Černe, Daniel C. Sigg, Lars M. Mattison, Paul A. Iaizzo, Damijan Miklavčič
Abstract
OBJECTIVE: The goal of our study was to determine the importance of electric field orientation in an anisotropic muscle tissue for the extent of irreversible electroporation damage by means of an experimentally validated mathematical model. METHODS: Electrical pulses were delivered to porcine skeletal muscle in vivo by inserting needle electrodes so that the electric field was applied in direction either parallel or perpendicular to the direction of the muscle fibres. Triphenyl tetrazolium chloride staining was used to determine the shape of the lesions. Next, we used a single cell model to determine the cell-level conductivity during electroporation, and then generalised the calculated conductivity changes to the bulk tissue. Finally, we compared the experimental lesions with the calculated field strength distributions using the Sørensen-Dice similarity coefficient to find the contours of the electric field strength threshold beyond which irreversible damage is thought to occur. RESULTS: Lesions in the parallel group were consistently smaller and narrower than lesions in the perpendicular group. The determined irreversible threshold of electroporation for the selected pulse protocol was 193.4 V/cm with a standard deviation of 42.1 V/cm, and was not dependent on field orientation. CONCLUSION: Muscle anisotropy is of significant importance when considering electric field distribution in electroporation applications. SIGNIFICANCE: The paper presents an important advancement in building up from the current understanding of single cell electroporation to an in silico multiscale model of bulk muscle tissue. The model accounts for anisotropic electrical conductivity and has been validated through experiments in vivo.