Histotripsy has been shown promising for non-invasive treatment of deep venous thrombosis. Important challenges remain, however, to perform a safe and accurate treatment in human patients. The objective of this work was to evaluate 1) the feasibility of this approach assisted by a robot to recanalize effectively a venous thrombosis in vivo and 2) the safety or our device on venous wall injury and risk of pulmonary embolism.

A femoral venous thrombosis of 9 pigs weighing 49.6kg was systematically created. To obtain occlusive thrombosis, we used a double jugular and femoral approach to position the balloons. A thrombosis was obtained after 2h of stasis associated with 50 IU of human thrombin. A 2.25MHz transducer (Imasonic©) centered by a linear probe (SL10-2, SuperSonic Imagine©) was used and cavitation was obtained in the center the vein. After manual determination of the thrombus, a 6-axis robotic arm was used to automatically move the transducer along the thrombus trajectory. Success of recanalization was evaluated by the flow restoration, evaluated with phlebography and colour-Doppler imaging (Figure 1). The safety was assessed by local hematoma research with ultrasound imaging and histological analysis of the lungs for embolism.

7 occlusive and 2 subocclusive venous thrombosis were obtained with a mean length of 2.8±0.4cm. Among them, only 7 were accessible for recanalization because 2 thromboses were too deep (>3cm). Recanalization was systematically obtained among the 6 occlusive cases, with improvement of flow in the case of partial thrombosis. No extravasation of contrast product or hematoma was observed with radioscopy and ultrasound imaging. The pulmonary arterial tree wasmacroscopically free from embolism.

Thrombotripsy performed at high frequency (2.25MHz) is an effective and safe tool to enable non-invasive and thrombolytic venous recanalization.