Characterizing reversible, irreversible, and calcium electroporation to generate a burst-dependent dynamic conductivity curve

Abstract

The relationships between burst number, reversible, irreversible, and calcium electroporation have not been comprehensively evaluated in tumor tissue-mimics. Our findings indicate that electroporation effects saturate with a rate constant (τ) of 20 bursts for both conventional and high frequency waveforms (R² > 0.88), with the separation between reversible and irreversible electroporation thresholds converging at 50 bursts. We find the lethal thresholds for calcium electroporation are statistically similar to reversible electroporation (R² > 0.99). We then develop a burst-dependent dynamic conductivity curve that now incorporates electroporation effects due to both the electric field magnitude and burst number. Simulated ablation and thermal damage volumes vary significantly between finite element models using either the conventional or new burst-dependent dynamic conductivity curve (p < 0.05). Lastly, for clinically relevant protocols, thermal damage is indicated to not begin until 50 bursts, with maximum nonthermal ablation volumes at 100 bursts (1.5-13% thermal damage by volume). We find that >100 bursts generated negligible increases in ablation volumes with 40-70% thermal damage by volume at 300 bursts. Our results illustrate the need for considering burst number in minimizing thermal damage, choosing adjuvant therapies, and in modeling electroporation effects at low burst numbers.

Keywords: Burst number; Calcium electroporation; Dynamic conductivity curve; Electroporation; Pulsed field ablation; Thermal damage.