Physiological changes may dominate the electrical properties of liver during reversible electroporation: Measurements and modelling.

This study presents electrical measurements (both conductivity during the pulses and impedance spectroscopy before and after) performed in liver tissue of mice during electroporation with classical electrochemotherapy conditions (8 pulses of 100 µs duration). A four-needle electrode arrangement inserted in the tissue was used for the measurements. The undesirable effects of the four-electrode geometry, notably concerning its sensitivity, were quantified and discussed showing how the electrode geometry chosen for the measurements can impact the results. Numerical modelling was applied to the information collected during the pulse, and to the impedance spectra acquired before and after the pulses sequence. Our results show that the numerical results were not consistent, suggesting that other collateral phenomena not considered in the model are at work during electroporation in vivo. We show how the modification in the volume of the intra and extra cellular media, likely caused by the vascular lock effect, could at least partially explain the recorded impedance evolution. In the present study we demonstrate the significant impact that physiological effects have on impedance changes following electroporation at the tissue scale and the potential need of introducing them into the numerical models. The code for the numerical model is publicly available at https://gitlab.inria.fr/poignard/4-electrode-system.

Dynamical modeling of tissue electroporation.

In this paper, we propose a new dynamical model of tissue electroporation. The model is based on equivalent circuit approach at the tissue. Considering two current densities from cells and extracellular matrix, we identify the macroscopic homogenised contribution of the cell membranes. Our approach makes it possible to define a macroscopic homogenised electric field and a macroscopic homogenised transmembrane potential. This provides a direct link between the cell scale electroporation models and the tissue models. Finite element method adapted to the new non-linear model of tissue electroporation is used to compare experiments with simulations. Adapting the phenomenological electroporation model of Leguèbe et al. to the tissue scale, we calibrate the tissue model with experimental data. This makes two steps appear in the tissue electroporation process, as for cells. The new insight of the model lies in the well-established equivalent circuit approach to provide a homogenised version of cell scale models. Our approach is tightly linked to numerical homogenisation strategies adapted to bioelectrical tissue modeling.

Improvements in the extraction of cell electric properties from their electrorotation spectrum.

In this paper, we propose a new approach to perform cell dielectric characterization from their electrorotation spectrum. At first, a variance analysis is carried out to quantify the dispersion in electrorotation spectra due to the different parameters involved. On this basis, the impact of each parameter is emphasized by weighing the spectrum with an appropriate frequency-dependent coefficient: this technique enables to minimize the coupling effects which deteriorate the accuracy of parameter extraction. In addition, the Nelder-Mead simplex algorithm used in the identification procedure is modified to account for bounded intervals in which the unknown parameters are expected to vary. Both these techniques have proven to give increased confidence levels compared to previous work reported in the literature.