Safety and feasibility of transvascular pulsedfield ablation for orthotopic liver tumor in a rabbit model

Local ablation is a cornerstone of hepatocellular carcinoma management. However, thermal techniques are unsuitable for perivascular tumors due to the heat-sink effect and risk of injury to adjacent critical structures. While non-thermal pulsedfield ablation (PFA) overcomes these limitations, its percutaneous needle-based delivery risks tract seeding and potential vascular injury. This study evaluates a novel transvascular PFA approach using intravascularly delivered electrodes. By circumventing percutaneous needle-based electrode insertion, this strategy may reduce puncture-related complications and enable the ablation of tumors adjacent to major vessels. A custom endovascular PFA electrode was developed. Candidate treatment parameters were selected based on computational modeling. Subsequent transvascular PFA was performed in healthy rabbits with electrodes in the portal vein and inferior vena cava, assessing safety and histology over 28 days. The feasibility of tumor ablation was then evaluated in a rabbit VX2 orthotopic liver tumor model. Based on simulations, a protocol of 800 V (corresponding to an electric field strength of 1000 V/cm across the 8-mm electrode gap) and 80 pulses was selected, at which the modeled field between electrodes exceeded a conservative irreversible electroporation threshold (600 V/cm) without predictive thermal injury. In vivo, the procedure caused no persistent alterations in vital signs. Histopathological analysis showed coagulative necrosis of the targeted liver parenchyma and extensive necrosis of VX2 tumor tissue within the ablation zone, followed by a characteristic inflammatory and fibrotic repair response. Although the perivascular parenchyma was ablated, the structural architecture of the portal vein and inferior vena cava was preserved. Re-endothelialization was evident by day 21. Apart from a transient surgery-related fibrinogen elevation, coagulation parameters showed no PFA-specific changes under perioperative anticoagulant and postoperative antiplatelet therapy. No vascular perforation, acute occlusion, or ablation-related hemorrhage occurred in any animal. Transvascular PFA achieved effective ablation of liver tissue and transplanted VX2 liver tumors adjacent to major vessels while preserving vascular architecture, without evidence of significant thermal injury and major vascular injury-related complication. These preliminary findings suggest that transvascular PFA is promising and innovative, yet further investigation is warranted for high-risk anatomical tumors.