Abstract
Deep vein thrombosis (DVT) is a major public health problem, affecting 600,000 Americans annually with a healthcare cost of $10 billion. Standard interventional techniques are not effective for the chronic thrombus components present in 27% to 43% of DVT cases. Histotripsy is a focused ultrasound therapy that employs the mechanical action of bubble clouds to ablate tissue and induce vigorous fluid mixing. We have demonstrated synergy between histotripsy and the thrombolytic recombinant tissue plasminogen activator (rt-PA) for dissolution of retracted venous clots in vitro. Here, the role of histotripsy-induced bubble activity in rt-PA clot dissolution will be discussed. The rt-PA thrombolytic efficacy of histotripsy pulses that nucleate bubble activity either via (1) shock wave scattering or (2) exceeding the intrinsic cavitation threshold of the clot will be presented. The impact of each histotripsy type on the formed elements that comprise the clot will be described, as well as the likelihood of containing mechanical activity within the target zone. Finally, the utility of passive cavitation imaging to quantify the bubble activity necessary for liquefaction of tissue-mimicking phantoms representative of acute and chronic pathologies will be presented.
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