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 μm 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. |