In Vitro and In Vivo High-Intensity Focused Ultrasound Thrombolysis

Abstract

To characterize the ability of high-intensity focused ultrasound to achieve thrombolysis in vitro and investigate the feasibility of this approach as a means of restoring blood flow in thrombus-occluded arteries in vivo. All experiments were approved by the Institutional Animal Care Committee. Thrombolysis was performed with a 1.51-MHz focused ultrasound transducer with pulse lengths of 0.1 to 10 milliseconds and acoustic powers up to 300 W. In vitro experiments were performed with blood clots formed from rabbit arterial blood and situated in 2-mm diameter tubing. Both single location and flow bypass recanalization experiments were conducted. In vitro clot erosion was assessed with 30-MHz ultrasound, with debris size measured with filters and a Coulter counter. In vivo clots were initiated in the femoral arteries of rabbits (n = 26). Cavitation signals from bubbles formed during exposure were monitored. In vivo flow restoration was assessed with 23-MHz Doppler ultrasound. At a single location, in vitro clot erosion volumes increased with exposure power and pulse length, with debris size reducing with increasing pulse length. Flow bypass experiments achieved 99.2% clot erosion with 1.1% of debris above 0.5 mm in size. In vivo, 10 milliseconds pulses were associated with bleeding, but at 1 millisecond, it was feasible to achieve partial flow restoration in 6 of the 10 clots with only 1 of the 10 showing evidence of bleeding. In all cases, thrombolysis occurred only in the presence of cavitation. High-intensity focused ultrasound thrombolysis is feasible as a means of restoring partial blood flow in thrombus-occluded arteries in the absence of thrombolytic agents. The potential for bleeding with this approach requires further investigation.