Effect of pulse repetition frequency of high-intensity focused ultrasound on in vitro thrombolysis

Vascular occlusion by the thrombi is the main reason for ischemic stroke and deep vein thrombosis. High intensity focused ultrasound (HIFU) and histotripsy or microtripsy pulses can effectively dissolve the blood clot with no use of thrombolytic agent and ultrasound contrast agent (microbubbles). In this study, HIFU bursts at the same duty cycle (2%) but varied pulse repetition frequency (PRF) from 1 Hz to 1000 Hz were delivered to in vitro porcine blood clot for 30 s. Thrombolysis efficiency initially increases slightly with the PRF, 86.4 +/- 103%, 89.9 +/- 11.9, and 92.9 +/- 12.8% at the PRF of 1 Hz, 10 Hz, and 100 Hz, respectively, without significant difference (p > 0.05), but then drops dramatically to 37.9 +/- 6.9% at the PRF of 1000 Hz (p < 0.05). The particle size in the supernatant of dissolution is 547.1 +/- 129.5 nm, which suggests the disruption of thrombi into the subcellular level. Thrombi motion during HIFU exposure shows violent motion and significant curling at the low PRF, rotation about its axis with occasional curling at the moderate PRF, and localized vibration at the high PRF due to the generation of acoustic radiation force and streaming. Quantitative analysis of recorded motion shows the axial displacement decreases with the PRF of delivered HIFU bursts, from 3.9 +/- 1.5 mm at 1 Hz to 0.7 +/- 0.4 mm at 1000 Hz. Bubble cavitation during HIFU exposure to the blood clot was also monitored. The increase of PRF led to the increase of inertial cavitation but the decrease of stable cavitation. In summary, the PRF of delivered HIFU bursts at the same output energy has a significant effect on the thrombi motion, bubble cavitation activities, and subsequently thrombolysis efficiencies. (C) 2016 Elsevier B.V. All rights reserved.