In-vivo study of non-invasive thrombolysis by histotripsy in a porcine model

Thrombolysis is currently performed using either thrombolytic drugs or catheter-based interventions, both of which have significant associated risks. Previously, it was demonstrated that histotripsy cavitation ultrasound therapy can break down blood clots rapidly in-vitro guided by imaging feedback. This study is an initial evaluation of histotripsy´s ability to non-invasively dissolve clots in-vivo. A venous thrombosis model was developed using two balloon catheters inserted into the femoral vein of porcine subjects, then injecting thrombin in an occluded region of the vessel between the balloons. Both partially and fully occlusive clots were formed, with average length of 2 cm. Treatment was performed using a 1 MHz, spherically focused transducer coupled to the legs of the subject by a water bath. Therapy consisted of 5 cycle ultrasound pulses delivered at a rate of 1 kHz with a peak negative focal pressure (p-) of 14-19 MPa. The treatment was guided by ultrasound imaging. We were able to easily visualize clots on a B-Mode image, and target them such that the bubble cloud generated by histotripsy was entirely within the vessel. Histotripsy was able to break down the clots, as indicated by a reduction of echogenicity within the vessel walls, and in some cases improved flow through the vessel on color Doppler imaging. Vessels showed minimal damage post-treatment. These results indicate that histotripsy has potential to be an effective noninvasive thrombolysis technique.