Characterization of Nonlinearity and Dispersion in Tissue Impedance During High-Frequency Electroporation

Objective: The use of high-voltage, high-frequency bipolar pulses (HFBPs) is an emerging electroporation-based therapy for the treatment of solid tumors. In this study, we quantify the extent of nonlinearity and dispersion during the HFBP treatment.

Methods: We utilize flat-plate electrodes to capture the impedance of the porcine liver tissue during the delivery of a burst of HFBPs of widths 1 and 2  $\mu$s at different pulse amplitudes. Next, we fit the impedance data to a frequency-dependent parallel RC network to determine the conductivity and permittivity of the tissue as a function of frequency, for different applied electric fields. Finally, we present a simple model to approximate the field distribution in the tissue using the conductivity function at a frequency that could minimize the errors due to approximation with a nondispersive model.

Results: The conductivity/permittivity of the tissue was plotted as a function of frequency for different electric fields. It was found that the extent of dispersion reduces with higher applied electric field magnitudes.

Conclusion: This is the first study to quantify dispersion and nonlinearity in the tissue during the HFBP treatment. The data have been used to predict the field distribution in a numerical model of the liver tissue utilizing two needle electrodes.

Significance: The data and technique developed in this study to monitor the electrical properties of tissue during treatment can be used to generate treatment-planning models for future high-frequency electroporation therapies as well as provide insights regarding treatment effect.