Prior studies have left the selection of high frequency irreversible electroporation (H-FIRE) pulse parameters in glioma ablation ambiguous. We developed a pulse waveform-depended glioma ablation model for the first time, in which the dynamic conductivity of tumor and gray/white tissues were determined based on the peak frequency of H-FIRE pulses. Four typical H-FIRE pulses (5-1-5-1 μs, 5-5-5-5 μs, 10-1-10-1 μs, 10-5-10-5 μs) were selected to investigate the effect of pulse duration and interphase delay on glioma ablation. Firstly, the optimal voltage was determined as the minimal voltage required to completely ablate the tumor. It was observed that the optimal voltage gradually decreased with increasing pulse duration and interphase delay. Specifically, the 5-1-5-1 μs pulse required 2650 V, whereas the 10-1-10-1 μs pulse required a lower voltage of 1950 V. Secondly, we assessed the impacts of nerve excitation and ablation of normal tissue (white matter) around the tumor at these optimal voltages. At the 5-1-5-1 μs pulse, the neural excitability and white matter ablation volume were minimal, despite the maximum tissue temperature rise. At the same time, variations in pulse duration had a more significant impact on white matter ablation and neural excitation than interphase delays. Finally, sensitivity analysis identified the lethal electric field threshold (LEFT) of white matter as the most critical parameter affecting white matter ablation outcomes. In this study, the effects of pulse parameters were systematically compared from the perspective of frequency, enriching the internal mechanism of changes in pulse parameters affecting glioma treatment.
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