For irreversible-electroporation (IRE)-based therapies, the underlying electric field distribution in the target tissue is influenced by the electroporation-induced conductivity changes and is important for predicting the treatment zone. Objective: In this study, we characterized the liver tissue conductivity changes during high-frequency irreversible electroporation (H-FIRE) treatments of widths 5 and 10 μs and proposed a method for predicting the ablation zones. Methods: To achieve this, we created a finite-element model of the tissue treated with H-FIRE and IRE pulses based on experiments conducted in an in-vivo rabbit liver study. We performed a parametric sweep on a Heaviside function that captured the tissue conductivity versus electric field behavior to yield a model current close to the experimental current during the first burst/pulse. A temperature module was added to account for the current increase in subsequent bursts/pulses. The evolution of the electric field at the end of the treatment was overlaid on the experimental ablation zones determined from hematoxylin and eosin staining to find the field thresholds of ablation. Results: Dynamic conductivity curves that provided a statistically significant relation between the model and experimental results were determined for H-FIRE. In addition, the field thresholds of ablation were obtained for the tested H-FIRE parameters. Conclusion: The proposed numerical model can simulate the electroporation process during H-FIRE. Significance: The treatment planning method developed in this study can be translated to H-FIRE treatments of different widths and for different tissue types.

Pulsed electric fields have recently been the focus of considerable attention because of their potential application in biomedicine. However, their practical clinical applications are limited by poor understanding of the interaction mechanism between pulsed electric fields and cells, particularly in the process of electroporation and its effect on parameter selection. This paper established a multishelled dielectric model based on finite elements to simulate and analyze the processes involved in electroporation. In particular, the processes include the dynamic development of the pore radius and electroporation region: the distribution of recoverable, nonrecoverable, and nonelectroporation areas on the cell; and the influence of pulse parameters on varying degrees of electroporation. Results showed that membrane conductivity, pore density, transmembrane potential, and distribution of pore radii are functions of time and position on the cell. The electroporation areas were divided into recoverable, nonrecoverable, and no-electroporation pores. For 10 μs, 1.5-kV/cm pulse was observed in the regions exposed to sufficiently high transmembrane voltage (1 V), electroporation occurred, membrane conductivity and pore density (up to 10 ¹⁶ /m ² rapidly increased with time, and electroporation areas increased gradually and were mainly distributed in the range 0°-70° (recoverable pore [0°, 35°], nonrecoverable pore [35°, 70°], and no-electroporation pore [70°, 90°]). Electric field strength was the major factor that induced electroporation, particularly in the recoverable pore, but it had minimal effect on pore expansion. However, pulse duration affects the nonrecoverable pore, such that the high-intensity wide pulse is more useful in the field of irreversible electroporation. The high-intensity short pulse can increase permeability and maintain cell viability.

High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay (d ₁ )-negative phase-interpulse delay (d ₂ ) pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively. Objective: We sought to determine whether modifications to the delays within H-FIRE bursts could yield a more desirable clinical outcome in terms of ablation volume versus extent of tissue excitation. Methods: We used a modified spatially extended nonlinear node (SENN) nerve fiber model to evaluate excitation thresholds for H-FIRE bursts with varying delays. We then calculated non-thermal tissue ablation, thermal damage, and excitation in a clinically relevant numerical model. Results: Excitation thresholds were maximized by shortening d ₁ , and extension of d ₂ up to 1,000 μs increased excitation thresholds by at least 60% versus symmetric bursts. In the ablation model, long interpulse delays lowered the effective frequency of burst waveforms, modulating field redistribution and reducing heat production. Finally, we demonstrate mathematically that variable delays allow for increased voltages and larger ablations with similar extents of excitation as symmetric waveforms. Conclusion: Interphase and interpulse delays play a significant role in outcomes resulting from H-FIRE treatment. Significance: Waveforms with short interphase delays (d ₁ ) and extended interpulse delays (d ₂ ) may improve therapeutic efficacy of H-FIRE as it emerges as a clinical tissue ablation modality.

Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.

Objective: Tissue electroporation is achieved by applying a series of electric pulses to destabilize cell membranes within the target tissue. The treatment volume is dictated by the electric field distribution, which depends on the pulse parameters and tissue type and can be readily predicted using numerical methods. These models require the relevant tissue properties to be known beforehand. This study aims to quantify electrical and thermal properties for three different tissue types relevant to current clinical electroporation. Methods: Pancreatic, brain, and liver tissue were harvested from pigs, then treated with IRE pulses in a parallel-plate configuration. Resulting current and temperature readings were used to calculate the conductivity and its temperature dependence for each tissue type. Finally, a computational model was constructed to examine the impact of differences between tissue types. Results: Baseline conductivity values (mean 0.11, 0.14, and 0.12 S/m) and temperature coefficients of conductivity (mean 2.0, 2.3, and 1.2 % per degree Celsius) were calculated for pancreas, brain, and liver, respectively. The accompanying computational models suggest field distribution and thermal damage volumes are dependent on tissue type. Conclusion: The three tissue types show similar electrical and thermal responses to IRE, though brain tissue exhibits the greatest differences. The results also show that tissue type plays a role in the expected ablation and thermal damage volumes. Significance: The conductivity and its changes due to heating are expected to have a marked impact on the ablation volume. Incorporating these tissue properties aids in the prediction and optimization of electroporation-based therapies.

Chemoresistance causes tumor recurrence and metastasis, resulting in poor clinical outcomes and low survival, and has been considered an obstacle to tumor therapy. The development of novel therapeutic approaches that can effectively kill chemoresistant tumor cells (CRTCs) is therefore critical to overcoming these obstacles. Objective: Here, we introduce an emerging physical feature-based therapeutic approach based on nanosecond pulsed electric fields (nsPEFs). The goal of this study is to investigate the effect of nsPEFs on CRTCs. Methods: The cell viability, ablation effects on a 3D-cultured scaffold, and lethal thresholds of nsPEFs were evaluated according to fluorescence staining assays. Results: nsPEF treatment preferentially affected chemoresistant cells (A549/CDDP) with a higher cell viability inhibition ability/cell death rate, larger ablation area, and lower ablation threshold compared to their respective homologous tumor cells (A549). The experimental and theoretical studies suggested that nsPEFs displayed selective behavior toward intracellular structures. With this selective character, nsPEFs can induce higher electroporation effects (e.g., higher pore number, larger electroporation area, and faster fluorescence dissipation on the nuclear envelope) on CRTCs due to their larger nuclear size and cell membrane capacitance. Conclusion: These findings demonstrated that nsPEFs induced preferential ablation of CRTCs over their respective homologous tumor cells. Significance: This study provides an experimental and theoretical basis for the study of killing CRTCs by electrical treatments and suggests potential applications in the optimization of novel anti-chemoresistance methods.