High-frequency Bipolar Asymmetric Pulses Enhance Tissue Ablation Efficacy with Low Neuromuscular Stimulation

As a novel tumor ablation technology, irreversible electroporation (IRE) has gradually become one of the important research directions in the field of tumor therapy, owing to its advantages of non-thermal effect and tissue selectivity. However, its clinical application is limited by the key issue of muscle contractions induced by neural stimulation triggered by pulsed electric fields (PEF). This issue has a significant impact on patients' intraoperative treatment and postoperative rehabilita-tion. Although the newly proposed high-frequency irreversible electroporation (H-FIRE) can alleviate neuromuscular stimula-tion, its ablation efficacy is significantly reduced due to the constraint of the "bipolar cancellation" effect. Existing pulse optimization strategies struggle to balance the dual requirements of neuromuscular stimulation inhibition and ablation efficiency improvement. To address this core contradiction, this study proposes a high-frequency bipolar asymmetric pulse (H-FBAP) protocol. This protocol not only retains H-FIRE's advantage of low neuromuscular stimulation but also effectively suppresses the bipolar cancellation effect by optimizing the asymmetric configuration of pulses, thus enhancing ablation efficacy. Meanwhile, this study summarizes the conditions for H-FBAP to inhibit neural excitation and the rules for improving ablation efficiency. The outcomes regarding ablation efficacy and muscle contraction were validated via simulation, in vitro experiments, and animal studies. The results demonstrated that, compared with H-FIRE, H-FBAP increased the ablation area by up to 88.77%, while its muscle contraction intensity was only 19.8% of that of IRE at the same amplitude. This study provides a novel technical solution for addressing the core bottleneck in PEF ablation technology.