Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings

Abstract

Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole target tissue; therefore, tissue heterogeneity may affect the treatment outcome. In this study, we investigate electroporation in the liver using a numerical mesoscale tissue model. We numerically reconstructed four ECT experiments in healthy porcine liver and computed the electric field distribution using our treatment planning framework. We compared the computed results with histopathological changes identified on microscopic images after treatment. The mean electric field threshold that best fitted the zone of coagulation necrosis was 1225 V/cm, while the mean threshold that best fitted the zone of partially damaged liver parenchyma attributed to IRE was 805 V/cm. We evaluated how the liver macro- and microstructures affect the electric field distribution. Our results show that the liver microstructure does not significantly affect the electric field distribution on the level needed for treatment planning. However, major hepatic vessels and portal spaces significantly affect the electric field distribution, and should be considered when planning treatments.

Liver‐tumor mimics as a potential translational framework for planning and testing irreversible electroporation with multiple electrodes

“…The higher demand of voltage to eradicate endothelial cells, compared to liver‐tumor cells, supports the findings reported for non‐transformed BEAS‐2B cells 23 . The poor response of endothelial cells to IRE, particularly exhibited in co‐cultured hydrogels, aligns with its reported significant impact on the EF distribution 24 . This trend may be observed in Figures 2b and 3d, and Figure S1, for an alternative experiment in which the HUVEC‐GFP hydrogel was pipetted directly in the well center resembling a semi‐sphere.…”

“…23 The poor response of endothelial cells to IRE, particularly exhibited in cocultured hydrogels, aligns with its reported significant impact on the EF distribution. 24 This trend may be observed in Figures 2b and 3d, and Figure S1, for an alternative experiment in which the HUVEC-GFP hydrogel was pipetted directly in the well center resembling a semisphere. Therein, the ablation zone diminishes concentrically through the Hep-G2 hydrogel from the bottom to the top, whereas the viable extent becomes inversely larger through the HUVEC-GFP hydrogel.…”

Safety and Feasibility of Analgosedation for Electrochemotherapy of Liver Lesions

“…As an alternative to thermal ablation, electrochemotherapy (ECT) was introduced for improving ablative results, being characterized by nonthermal mechanism, that means without heat sink effect and harm to vessels, with more apoptosis than necrosis, based on the pulsed electrical field instead of joule heating, with consequent easier to simulate the physics and better plannable intervention [ 27 ].…”

A Multiscale Computational Model of Skeletal Muscle Electroporation Validated Using In Situ Porcine Experiments

“…Thus there were no tissues adjacent to the treated muscle present that could affect the electric field distribution within the treated muscle tissue and its conductivity. The microstructure of the tissue also has no significant influence on the distribution of the electric field on a macroscopic level and can therefore be neglected, but it does influence the distribution of the electric field on a microscopic level / locally [45], [60]. As can be observed in Fig.…”

“…The increase in bulk tissue conductivity due to or during electroporation has been described previously and was used to control pulse delivery, thus limiting the damage induced due to electroporation [43]. It has been described by various functional dependencies of conductivity as a function of local electric field [44], [45], but until recently was not explicitly linked to changes in membrane conductivity. The conductivity of the cell membrane and consequently the conductivity of the cell is increased in the direction of the electric field of the delivered electroporative pulses, i.e., it can be said that electroporation induces or increases the anisotropy of the tissue [30].…”