Induction of rapid, reproducible hepatic ablations using next-generation, high frequency irreversible electroporation (H-FIRE) in vivo

Introduction: Irreversible electroporation (IRE) offers an alternative to thermal tissue ablation in situ. High-frequency IRE (H-FIRE), employing ultra-short bipolar electrical pulses, may overcome limitations associated with existing IRE technology to create rapid, reproducible liver ablations in vivo. Methods: IRE electrodes (1.5 cm spacing) were inserted into the hepatic parenchyma of swine (n = 3) under surgical anesthesia. In the absence of paralytics or cardiac synchronization five independent H-FIRE ablations were performed per liver using 100, 200, or 300 pulses (2250 V, 2-5-2 mu s configuration). Animals were maintained under isoflurane anesthesia for 6 h prior to analysis of ablation size, reproducibility, and apoptotic cell death. Results: Mean ablation time was 230 +/- 31 s and no EKG abnormalities occurred during H-FIRE. In 1/15 HFIRE's minor muscle twitch (rectus abdominis) was recorded. Necropsy revealed reproducible ablation areas (34 +/- 4 mm(2), 88 +/- 11 mm(2) and 110 +/- 11 mm(2); 100-, 200- and 300-pulses respectively). Tissue damage was predominantly apoptotic at pulse delivery <= 200 pulses, after which increasing evidence of tissue necrosis was observed. Conclusion: H-FIRE can be used to induce rapid, predictable ablations in hepatic tissue without the need for intraoperative paralytics or cardiac synchronization. These advantages may overcome limitations that restrict currently available IRE technology for hepatic ablations.