Low-duty-cycle pulsed ultrasound for ex vivo liver tissue ablation: thermal safety, lesion conformity, and vascular structure preservation

OBJECTIVE: To investigate the physical mechanisms and engineering efficacy of low-duty-cycle pulsed ultrasound (histotripsy) in overcoming the heat sink effect and preserving major hepatic vessels.Impact Statement: This study provides a highly conformal, non-thermal ablation strategy that eliminates blood flow cooling effects while maintaining vascular integrity, offering superior precision over traditional methods. INTRODUCTION: Conventional thermal ablation for hepatocellular carcinoma is limited by the "heat sink effect," causing marginal residual tumors and risking irreversible damage to major blood vessels. Quantitative investigations defining the thermal safety boundaries of histotripsy to overcome these limitations are currently lacking. METHODS: Combining simulation optimization and ex-vivo validation, an acoustic-thermal coupled model identified an optimal protocol (2.0 MHz, 37 MPa, 0.5% duty cycle). Ex-vivo porcine liver experiments compared this cavitation ablation head-to-head with continuous-wave thermal ablation near major vessels, assessing morphology, Conformity Index (CI), and vascular integrity. RESULTS: Simulations showed a 0.5% duty cycle kept peak temperatures below the 60°C denaturation threshold. Ex-vivo, the cavitation group achieved homogeneous liquefaction, sharp boundaries, and preserved adjacent vessels, yielding a 96.8 ± 2.1% CI. The thermal group suffered from the cooling effect, showing irregular defects and a lower CI of 71.2 ± 15.6% (P < 0.01). CONCLUSION: Low-duty-cycle pulsed ultrasound provides a safe, highly conformal non-thermal ablation solution that successfully overcomes the heat sink effect and preserves critical vascular architecture.