New non-invasive ultrasonic device for venous recanalization: assessment of feasibility and safety of thrombotripsy at 2.25 MHz in an in vitro model of recent venous thrombosis

Objective Persistent occlusion following venous thrombosis is associated with an increased risk of post-thrombotic syndrome. Early venous recanalization may prevent this complication. Ultrasonic histotripsy fractionates soft tissue through a cavitation cloud generated by an external transducer. We aimed at testing this technique as a drug-free thrombolysis on recent in vitro clots. Methods Venous thrombosis conditions were reproduced in vitro, using human blood clotting by stasis in silicone tubes (6 mm internal diameter, close to the femoral vein), in a 37 °C water-bath, then mounted on a saline solution at a 25 mmHg constant pressure. The ultrasound device was composed of dual 2.25 MHz transducers centred by a 7-MHz linear probe. A single cavitation cloud was generated at a 3.2-cm depth from the device. Thrombotripsy was performed by longitudinal passages along of the whole thrombus at 3 pre-specified speeds (1; 2; 3 mm/s). Restored outflow was assessed every 3 passages. Results 24 occlusive successive thrombi of 2.5 cm meanu0027s length were evaluated. Flow restoration was systematically obtained by the succession of 9 passages. An efficient flow restoration was carried out in 6 min maximum. Regardless from the deviceu0027s speed, an average time of 76 ± 17 s was necessary to obtain a 70% flow recovery ( Fig. 1 ). A speed of 1 mm.s −1 allowed an efficient recanalization (80% ± 7%) after only 3 passages, corresponding to a treatmentu0027s duration of 1.5 min with the lowest variability. The cavitation drilled a circular channel of 1.7 mm mean diameter throughout the clot with a 1.5-mm thick residual thrombus coating the tube. Debris analysis found no debris u003e 200 μm with 92% of debris  Conclusion Our dual transducers thrombotripsy device performed a fast recanalization of whole-blood thrombus without any parietal alteration or bulky debris formation. This new technology opens the field to a drug-free and non-invasive thrombolysis.