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.

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.

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.

Given its nonthermal property and other advantages, irreversible electroporation (IRE) has quickly translated into clinical applications. An increasing number of clinical cases using IRE have also revealed crucial issues. The uneven distribution of the electric field caused by the heterogeneity of biological tissues has not been completely and effectively addressed to date. The use of high-frequency monopolar pulse bursts (HFMPBs) is expected to solve this problem. The high-frequency content of the HFMPB is used to ensure the uniform distribution of the electric field in the tissue. A temperature increase similar to that of the conventional pulse method does not cause thermal damage and results in a killing effect similar to that of the conventional technique. Meanwhile, the subpulse has a pulse duration of 1– $100~\mu \text{s}$ , which remains unexplored and may induce new cell responses. This paper analyzes the HFMPB based on the frequency domain and infers that the cell death pathways under this pulse induce necrosis and other processes, such as apoptosis. The phosphatidylserine externalization rate had a peak value at a different inner frequency of HFMPB when the electric field was 1 kV/cm for melanoma cells. This new type of pulse is expected to solve the problem of the uneven distribution of the electric field without altering the cell killing effect. If this effect is also verified in tissue ablation, these new types of pulses will promote the clinical application of IRE.