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

OBJECTIVE

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.

METHODS

INSPIRE was administered to healthy swine liver in vivo via a percutaneous single applicator and grounding pad approach. Using 45°C temperature control, 6000V waveforms consisting of 750ns, 1000ns, or 2000ns 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.

RESULTS

Pulse duration did not significantly affect treatment volumes, however, dose was found to be a critical factor affecting treatment outcomes. For 0.0025s doses, treatment volumes of 1.3±0.6cm (2.4x0.9cm) were created in 0.3 minutes. This increased to 12.8±4.8 cm (9.7 minutes, 3.9x2.5cm) for 0.04s doses. No significant changes in troponin levels were found.

CONCLUSION

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 0.02s with treatment times between 2-4 minutes.

SIGNIFICANCE

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.