Non-invasive thrombolysis using histotripsy beyond the “intrinsic” threshold (microtripsy)

Abstract

Histotripsy has been demonstrated as a non-invasive, drug-free, image-guided thrombolysis method using cavitation alone. Microtripsy is a new histotripsy approach, where cavitation is generated using 1-cycle ultrasound pulses with negative pressure exceeding a threshold intrinsic to the medium. We hypothesize that, using microtripsy, cavitation can be generated entirely within the vessel lumen, without contacting the vessel wall. Microtripsy was used to create a flow channel through a clot in a vessel-mimicking phantom by scanning the therapy focus through the clot at a pre-set interval. Different scan intervals, doses, and strategies (single focus vs. electrical-steered multi-foci) were tested in both unretracted and retracted clots. The flow channel size, thrombolysis rate, and clot debris particle sizes were measured. A cavitation cloud and flow channel was successfully generated and completely confined within the 6.5 mm-diameter vessel lumen through unretracted and retracted clots. A 1-4 mm channel was created in unretracted clots, at thrombolysis rate of 3.3 min/cm. Using an electrical-steered multi-foci method, a 1–2.5 mm channel was generated through retracted clots, at thrombolysis rate of 5.5 min/cm. The debris particles generated were no greater than 150 μm. The results show the potential of microtripsy for precise and effective clot recanalization, minimizing risks of vessel damage and embolism.