Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses

Abstract

BackgroundFor electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. In response to conventional, unipolar pulses, the electrical impedance of a tissue varies as a function of the local electric field, leading to a redistribution of the field. These dynamic impedance changes, which depend on the tissue type and the applied electric field, need to be quantified a priori, making mathematical modeling complicated. Here, it is shown that the impedance changes during high-frequency, bipolar electroporation therapy are reduced, and the electric field distribution can be approximated using the analytical solution to Laplace's equation that is valid for a homogeneous medium of constant conductivity.MethodsTwo methods were used to examine the agreement between the analytical solution to Laplace's equation and the electric fields generated by 100 µs unipolar pulses and bursts of 1 µs bipolar pulses. First, pulses were applied to potato tuber tissue while an infrared camera was used to monitor the temperature distribution in real-time as a corollary to the electric field distribution. The analytical solution was overlaid on the thermal images for a qualitative assessment of the electric fields. Second, potato ablations were performed and the lesion size was measured along the x- and y-axes. These values were compared to the analytical solution to quantify its ability to predict treatment outcomes. To analyze the dynamic impedance changes due to electroporation at different frequencies, electrical impedance measurements (1 Hz to 1 MHz) were made before and after the treatment of potato tissue.ResultsFor high-frequency bipolar burst treatment, the thermal images closely mirrored the constant electric field contours. The potato tissue lesions differed from the analytical solution by 39.7 ± 1.3 % (x-axis) and 6.87 ± 6.26 % (y-axis) for conventional unipolar pulses, and 15.46 ± 1.37 % (x-axis) and 3.63 ± 5.9 % (y-axis) for high- frequency bipolar pulses.ConclusionsThe electric field distributions due to high-frequency, bipolar electroporation pulses can be closely approximated with the homogeneous analytical solution. This paves way for modeling fields without prior characterization of non-linear tissue properties, and thereby simplifying electroporation procedures.

Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation

“…If electroporation is a stochastic process driven by increasing TMPs, our model would predict similar results if electroporation were explicitly considered. Further, Gowrishankar and Weaver (23) showed that a transport lattice model predicts a more homogeneous electric field and current density distribution when electrical pulses of shorter pulse widths are applied, corroborating experimental results of Sweeney et al (18) and Bhonsle et al (24).…”

“…S10 and S11). It has been previously observed that H-FIRE treatment generates more homogenous lesions (2,24,(27)(28)(29)(30)(31) and in this article, we offer an explanation for that phenomenon.…”

Avoiding nerve stimulation in irreversible electroporation: a numerical modeling study

“…In addition the medium was considered to be purely conductive with a constant conductivity and it is agreed that electroporation alters the conductivity of tissues (Corovic et al 2013); although such alteration is not as remarkable in the case of high frequency bipolar bursts as it is in the case of conventional pulses (Bhonsle et al 2015). These circumstances significantly alter the electric field distribution and, normally, would have to be modeled in an electroporation study.…”

Quantification of cell membrane permeability induced by monopolar and high-frequency bipolar bursts of electrical pulses

“…A notable recent improvement in IRE has been termed high-frequency IRE (HF-IRE) and replaces the long monopolar pulsing schemes traditionally used in IRE (80 × 100 µs-long pulses delivered at 1 Hz) with bursts of short bipolar pulses [20]. These bursts of short pulses partially mitigate intra-operative impedance changes [51] and virtually eliminate muscle contractions [52,53,54,20] during the treatment to potentially improve both current treatment planning algorithms [20,55] and the procedural safety for the patient due to the reduced need for neuroparalytic drugs typically required to inhibit muscle contraction. For the same reason, bursts of short pulses could also be advantageous in ECT and GET, which have historically utilized pulse widths of hundreds of microseconds to milliseconds to permeabilize the cell membrane.…”