Non-invasive thrombolysis induced by histotripsy pulsed cavitation ultrasound therapy

Current thrombolytic techniques have significant drawbacks including risks of excessive bleeding and infection. The purpose of this study was to evaluate histotripsy as a new method of thrombolysis. Histotripsy uses short, intense ultrasound pulses to fractionate soft tissue through controlled cavitation. Histotripsy was applied to clots in-vitro using a 1-MHz focused transducer, 5-cycle pulses at a pulse repetition frequency of 1 kHz and peak negative pressures between 2-12 MPa. An ultrasound imaging transducer was used for targeting and monitoring of treatment. Backscatter of the therapy pulse was recorded to detect initiation of a cavitation cloud. Debris size distributions were measured using filter paper and a Coulter Counter. Histotripsy was able to break down clots weighing > 300 mg within 300 seconds of treatment. Thrombolysis was only observed at peak negative pressures >= 6 MPa, with the initiation of a cavitation bubble cloud at the transducer focus. Over 96% of the debris weight was < 5 mum diameter. During ultrasound application, it was observed that clot fragments were spontaneously attracted to and trapped near the transducer focus, and further broken down. This phenomenon may be applicable as a means to prevent embolism during histotripsy and other procedures.