Using Voltage to Control Ablation Size in Integrated Nanosecond Pulse Irreversible Electroporation (INSPIRE) Treatments

Purpose: This study shows the impact of applied voltage on Integrated Nanosecond Pulse Irreversible Electroporation (INSPIRE) administered via a single applicator and grounding pad approach in a healthy liver model.

Materials and Methods: Healthy swine livers were accessed via a percutaneous, ultrasound-guided approach. INSPIRE treatments were delivered using an actively cooled single applicator and distal grounding pad. Treatments were delivered at 3000 V, 4500 V, or 6000 V using 1000 ns or 2000 ns waveforms with a 0.02 s dose and a 45 ºC temperature set point. One-week post-treatment, contrast-enhanced CTs were acquired before animals were euthanized and livers collected for analysis. A COMSOL model was used to derive the corresponding lethal electric field thresholds.

Blood samples were acquired pre-treatment, immediately post-treatment, and prior to euthanasia. Troponin levels were evaluated as a measure of cardiac safety.

Muscle stimulation was compared between traditional IRE pulses and INSPIRE treatments with or without neuromuscular paralytic. Stimulation was quantified by videoing an array of markers drawn on the skin which were then tracked in MATLAB to derive acceleration.

Results: All INSPIRE treatments were completed successfully without causing intraoperative adverse events. Ablations were visible on ultrasound within 10 minutes post-treatment. Each treatment took approximately 2-8 minutes to deliver. The largest ablations, achieved with the 2000 ns waveform at 6000 V, measured 4.4 ± 0.7 cm by 2.9 ± 0.1 cm with a lethal threshold of 322 ± 61 V/cm.

No elevated troponin levels indicative of cardiac damage occurred for any INSPIRE treatments. Elevated troponin levels were observed in the traditional IRE group during the muscle stimulation experiments, which increased from 0.252 ng/mL prior to treatment to 2.98 ng/mL after treatment. After one week, the troponin level returned to a value below the detection threshold.

Conclusion: INSPIRE can safely achieve predictable and substantially larger ablations than existing single needle IRE technologies in less time. Joule heating was adequately addressed by active temperature control and applicator cooling. Ablations were visible on ultrasound soon after completion, which may reduce risk of incomplete ablation in a clinical setting. Treatment zones can be adjusted via the applied voltage simplifying treatment planning. Finally, INSPIRE mitigates muscle stimulation and may eliminate the need for cardiac synchronization, improving its safety profile.