Electric Field Thresholds for Electroporation and Cell Death by Milli- To Nanosecond Pulses: How to Avoid Neuromuscular Stimulation in Cancer Ablation

Abstract

Pulsed electric field (PEF) ablation treatments utilize irreversible electroporation and are advantageous in their ability to target cellular components while leaving the vasculature and structural components intact. However, PEF therapies come with the known caveat of neuromuscular excitation outside of the ablation area, causing pain and involuntary muscle contraction. We performed a thorough examination of PEF ablation parameters, including pulse duration, pulse number, and frequency for both uni- and bipolar waveforms with the goal of minimizing neuromuscular excitation. This was done by measuring electroporation and ablation thresholds for 150 ns - 1 ms PEF, uni- and bipolar, delivered in 10-300 pulse trains at up to 1 MHz rates. The ratio between the measured ablation thresholds and already established nerve stimulation thresholds determines the span of neuromuscular effects beyond the ablated region. We found that this ratio is reduced more than 100-fold with the use of bipolar nanosecond-range PEF, in comparison to conventional methods using 100 µs unipolar pulses. This translates to a 10-fold reduction in the tissue radius excited by PEF treatments (see image). Additionally, packing nanosecond PEF into high-frequency bursts promises to reduce the number of neuromuscular responses with minimal impact on ablation efficacy. PEF ablation with bipolar nanosecond pulses is expected to produce far fewer neuromuscular side effects than conventional protocols for irreversible electroporation