Dose Is a Critical Factor Affecting Treatment Volumes for Integrated Nanosecond Pulse Irreversible Electroporation (INSPIRE).

Abstract

<h4>Objective</h4>The objective of this study was to investigate the effect of electrical dose on in vivo INSPIRE treatments which administer high voltage ultrashort alternating polarity electrical pulses with active temperature control.<h4>Methods</h4>INSPIRE was administered to healthy swine liver in vivo via a percutaneous single applicator and grounding pad approach. Using 45 °C temperature control, 6000 V waveforms consisting of 750 ns, 1000 ns, or 2000 ns bipolar pulses were administered to examine the effect of pulses approximately shorter than, equal to, and longer than the cell membrane charging time. Treatment volumes were assessed one week post treatment via computed tomography and cardiac safety was assessed via serum troponin analysis.<h4>Results</h4>Pulse duration did not significantly affect treatment volumes, however, dose was found to be a critical factor affecting treatment outcomes. For 0.0025 s doses, treatment volumes of 1.3±0.6 cm³ (2.4 × 0.9 cm) were created in 0.3 minutes. This increased to 12.8±4.8 cm³ (9.7 minutes, 3.9 × 2.5 cm) for 0.04 s doses. No significant changes in troponin levels were found.<h4>Conclusion</h4>This study demonstrated the in vivo safety of high voltage INSPIRE treatments without cardiac synchronization. There is a strong dose dependent effect on treatment volumes. Optimal treatment efficiency was found for treatment doses between 0.01 and 0.02 s with treatment times between 2-4 minutes.<h4>Significance</h4>Single applicator INSPIRE treatments significantly simplify treatment planning and clinical implementation versus traditional two to six applicator approaches. This study demonstrates that INSPIRE protocols can rapidly produce large spherical treatment zones while reducing treatment times by an order of magnitude compared to existing electroporation approaches.