3 years ago

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Bastien Arnal, Guillaume Goudot, Tristan Mirault, Bernard Le Bonniec, Mickael Tanter, Alexandre Galloula, Catherine Boisson-Vidal, Emmanuel Messas, Pascale Gaussem, Mathieu Pernot
Post-thrombotic syndrome, a frequent complication of deep venous thrombosis can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for a drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis. To reproduce venous thrombosis conditions, human whole blood was allowed to clot by stasis in silicone tubes (6 mm internal diameter) at a 30 cmH20 pressure, maintained during the whole experiment. We engineered an ultrasound device composed of dual 2.25 MHz transducers centered by a 6 MHz imaging probe. Therapeutic focus was generated at 3.2 cm depth from the probe. Thrombotripsy was performed by longitudinal scanning the thrombus at 3 different speeds: 1 mm.s-1 (n=6); 2 mm.s-1 (n= 6); 3 mm.s-1 (n= 12). Restored outflow was measured every 3 passages. Filters were placed to evaluate the debris size. 24 occlusive thrombi, of 2.5 cm mean length and 4.4 kPa mean stiffness, were studied. Flow restoration was systematically obtained by 9 subsequent passages (4.5 min maximum). By varying the device's speed, we found an optimal speed of 1 mm.s-1 to be efficient for a complete recanalization with 90 s (3 passages). Within 90 s, flow restoration was of 80, 62 and 74 % at respectively 1, 2 and 3 mm.s-1. For all groups, cavitation cloud drilled a 1.7 mm mean diameter channel throughout the clot. Debris analysis showed 92 % of debris <10 μm, with no fragment > 200 µm. .

Publisher URL: http://doi.org/10.1088/1361-6560/aa9506

DOI: 10.1088/1361-6560/aa9506

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