Abstract No. 495 Non-invasive liver tumor ablation using histotripsy in an in vivo subcutaneous murine hepatocellular carcinoma model

Abstract

Histotripsy is a non-thermal, non-invasive ultrasound (US) ablation method that fractionates tissue through the precise control of acoustic cavitation guided by real-time US imaging. Histotripsy has the potential to improve treatment consistency and precision compared to thermal-based ablation methods. This study evaluates the feasibility and tumor volume reduction effects of histotripsy for liver cancer ablation in an in vivo murine HCC model. Subcutaneous xenograft tumors were generated by injecting human HCC Hep3B cells into 14 NSG mice (acute group A: treated n = 9, control n = 1 and chronic group B: treated n = 2, control n = 2) and 6 NOD-SCID mice (chronic group C: treated n = 6). Once tumors reached >5 mm, mice were treated by histotripsy using a custom built 1 MHz histotripsy transducer attached to a motorized positioner guided by US imaging system. 1-2 cycle histotripsy pulses at 100 Hz PRF (p- >30 MPa) were applied to the tumor volume. MRI was performed pre- and posttreatment to assess tumor ablation. Group A was sacrificed within 3 days post treatment. Groups B and C were monitored weekly using caliper measurements and MRI for 3 months or until tumors reached ∼1.8 cm. Tumor, brain and lung tissues were harvested for histology. Histotripsy-generated cavitation cloud and the treated region were visible on US imaging enabling real-time feedback. In group A, histopathology showed that the targeted region was completely fractionated into acellular debris with a sharp boundary. In groups B and C, MRI revealed effective tumor volume reduction post treatment as the homogenate and edema were resorbed within 3 weeks. However, as the subcutaneous tumor does not allow sufficient treatment margin, residual viable tumor cells developed into tumor regrowth at 3-9 weeks after treatment. Treated mice in group B survived 2-3 times longer than the control mice and showed no signs of metastasis in the lung and brain. At the time of submission, group C mice are being monitored until study endpoint. This study demonstrates the potential of histotripsy for non-invasive liver tumor ablation. Future work will study the biological response in immune competent orthotopic liver tumor models.