Extended interpulse delays improve therapeutic efficacy of microsecond-duration pulsed electric fields.

Irreversible electroporation (IRE), or pulsed field ablation, employs microsecond-duration pulsed electric fields to generate targeted cellular damage without injury to the underlying tissue architecture. Biphasic, burst-type waveforms (termed high-frequency IRE, or H-FIRE) have garnered attention for their ability to elicit clinically relevant ablation volumes while reducing several undesirable side effects (muscle contractions/electrochemical effects) seen with monophasic pulses. Pulse width is generally the main (or only) parameter considered during burst construction, with little attention given to the delays within the burst. In this work, we tested the hypothesis that H-FIRE waveforms could be further optimized by manipulating only the interpulse delay between biphasic pulses within each burst. Using benchtop, ex vivo, and in vivo models, we demonstrate that extended interpulse delays (i.e., ~100 µs) reduce the severity of induced muscle contractions, alleviate mechanical tissue destruction, and minimize the chances of electrical arcing. Clinical Relevance- This proof-of-concept study shows that H-FIRE waveforms with extended interpulse delays provide several therapeutic benefits over conventional waveforms.