Deep vein thrombosis (DVT) is a condition characterized by the formation a blood clot in the deep veins of the legs and affects nearly two million Americans per year. Clinical treatments for DVT include thrombolytic drugs and catheter-based surgical procedures, both of which have significant drawbacks, such as invasiveness and risks of bleeding and infection. Guided by ultrasound imaging, histotripsy is a cavitation-based ultrasound therapy that fractionates tissue. Using our laboratory prototype, histotripsy fractionated in vitro clots into debris smaller than red blood cells at a speed fifty-fold faster tan current clinical thrombolysis methods. Using an in vivo porcine DVT model, histotripsy non-invasively eradicated the thrombus in 10 of 12 cases. By eliminating thrombolytic drugs and catheters, shortening the treatment time, and maintaining or possibly increasing the efficacy for clot removal, histotripsy has the potential to truly change the landscape of thrombosis therapy. The goal of this proposal is to advance the clinical translation of histotripsy thrombolysis. To achieve this goal, we propose the following three specific aims. 1) Design and build an integrated image-guided histotripsy thrombolysis system for DVT patients. 2) Develop two technical innovations (microtripsy and bubble-induced color Doppler feedback) to further improve the safety and efficacy of histotripsy thrombolysis. 3) Determine the in vivo safety and efficacy of the clinically designed histotripsy thrombolysis system through a comprehensive pre-clinical study in the porcine DVT model.
These aims are designed to obtain results that are crucial towards achieving approval from the United States Food and Drug Administration (FDA) to inaugurate the first clinical trial of histotripsy thrombolysis. In addition, our proposed comprehensive preclinical in vivo safety study will quantitatively measure all the possible adverse effects of cavitation, which will be essential for clinical translation of all cavitation-bsed thrombolysis techniques including histotripsy. While we are currently studying DVT, there are many other diseases which could benefit from this revolutionary new thrombolysis technique, including stroke, myocardial infarction, superficial vein thrombosis, and peripheral arterial and graft thrombosis. Each poses a significant clinical problem where histotripsy thrombolysis may improve upon current treatment methods.
Deep vein thrombosis (DVT) is a condition characterized by the formation a blood clot in the deep veins of the legs and affects nearly two million Americans per year. We propose to advance the clinical translation of histotripsy thrombolysis, a new non-invasive thrombolysis technique that has the potential to significantly improve the standard of care for DVT patients. There are many other diseases which could also benefit from this revolutionary thrombolysis technique, including stroke, myocardial infarction, superficial vein thrombosis, and peripheral arterial and graft thrombosis.
|Shi, Aiwei; Lundt, Jonathan; Deng, Zilin et al. (2018) Integrated Histotripsy and Bubble Coalescence Transducer for Thrombolysis. Ultrasound Med Biol 44:2697-2709|
|Macoskey, Jonathan J; Zhang, Xi; Hall, Timothy L et al. (2018) Bubble-Induced Color Doppler Feedback Correlates with Histotripsy-Induced Destruction of Structural Components in Liver Tissue. Ultrasound Med Biol 44:602-612|
|Shi, Aiwei; Xu, Zhen; Lundt, Jonathan et al. (2018) Integrated Histotripsy and Bubble Coalescence Transducer for Rapid Tissue Ablation. IEEE Trans Ultrason Ferroelectr Freq Control 65:1822-1831|
|Macoskey, Jonathan J; Hall, Timothy L; Sukovich, Jonathan R et al. (2018) Soft-Tissue Aberration Correction for Histotripsy. IEEE Trans Ultrason Ferroelectr Freq Control 65:2073-2085|
|Macoskey, J J; Choi, S W; Hall, T L et al. (2018) Using the cavitation collapse time to indicate the extent of histotripsy-induced tissue fractionation. Phys Med Biol 63:055013|
|Gerhardson, Tyler; Sukovich, Jonathan R; Pandey, Aditya S et al. (2017) Catheter Hydrophone Aberration Correction for Transcranial Histotripsy Treatment of Intracerebral Hemorrhage: Proof-of-Concept. IEEE Trans Ultrason Ferroelectr Freq Control 64:1684-1697|
|Gerhardson, Tyler; Sukovich, Jonathan R; Pandey, Aditya S et al. (2017) Effect of Frequency and Focal Spacing on Transcranial Histotripsy Clot Liquefaction, Using Electronic Focal Steering. Ultrasound Med Biol 43:2302-2317|
|Mancia, Lauren; Vlaisavljevich, Eli; Xu, Zhen et al. (2017) Predicting Tissue Susceptibility to Mechanical Cavitation Damage in Therapeutic Ultrasound. Ultrasound Med Biol 43:1421-1440|
|Vlaisavljevich, Eli; Gerhardson, Tyler; Hall, Tim et al. (2017) Effects of f-number on the histotripsy intrinsic threshold and cavitation bubble cloud behavior. Phys Med Biol 62:1269-1290|
|Lundt, Jonathan E; Allen, Steven P; Shi, Jiaqi et al. (2017) Non-invasive, Rapid Ablation of Tissue Volume Using Histotripsy. Ultrasound Med Biol 43:2834-2847|
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