Image-Guided Non-Invasive Ultrasonic Thrombolysis Using Histotripsy

使用组织解剖学进行图像引导无创超声溶栓

• 批准号: 8323999
• 负责人: Zhen Xu
• 金额: $ 49.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323999
• 关键词: Accounting; Acoustics; Affect; American; Arterial Embolization; Blood Clot; Blood coagulation; Bypass; Caliber; Cardiovascular Diseases; Catheters; Cell Nucleus; Cessation of life; Clinical; Coagulation Process; Data; Deep Vein Thrombosis; Dependence; Diagnosis; Dialysis procedure; Embolism; Erythrocytes; Evaluation; Family suidae; Feedback; Fibrinolytic Agents; Fractionation; Hemorrhage; Human; Image; In Vitro; Individual; Infection; Lead; Leg; Location; Maintenance; Measurement; Medical; Methods; Microbubbles; Modeling; Monitor; Normal tissue morphology; Operative Surgical Procedures; Pathologic Processes; Patients; Physiologic pulse; Procedures; Process; Pulmonary Embolism; Resolution; Risk; Seeds; Speed; Stroke; Structure of superficial vein; System; Techniques; Testing; Therapeutic Embolization; Thrombosis; Time; Tissues; Ultrasonics; Ultrasonography; Venous Thrombosis; Work; base; clinical application; deep vein; improved; in vitro Model; in vivo; particle; pressure; prevent; prototype; public health relevance; response; soft tissue; standard of care; thrombolysis

DESCRIPTION (provided by applicant): Thrombosis is the medical term for the process of pathologic blood clot formation, the key mechanism behind many cardiovascular diseases. For example, deep vein thrombosis (DVT) is a condition which affects nearly two million Americans annually and is commonly diagnosed as thrombosis in the deep veins of the legs. To treat DVT, the blood clots need to be removed, a process generally termed thrombolysis. Current clinical thrombolysis methods include catheter-based procedures and thrombolytic drugs, both of which have significant drawbacks including invasiveness and risks of bleeding and infection. To improve the clinical standard of thrombolysis, we propose to develop an ultrasonic thrombolysis technique that is non-invasive and carries virtually no risks of bleeding and infection. Our technique, which we call "histotripsy", uses controlled ultrasound cavitation to mechanically fractionate soft tissue non-invasively, guided by high resolution imaging. By initiating and maintaining the cavitating bubble cloud with appropriate ultrasound pulse sequences, a targeted tissue can be precisely fractionated with a very narrow boundary between affected and normal tissue. As applied to thrombolysis, our preliminary data show that histotripsy can fractionate a blood clot at a speed fifty-fold faster than any current clinical thrombolysis method. Histotripsy breaks down blood clots into tiny particles that are smaller than red blood cells. As histotripsy-induced cavitating bubbles are easily detected acoustically, histotripsy thrombolysis can be guided and monitored by real-time ultrasound imaging. We propose to further improve and optimize histotripsy for safe and efficient non-invasive thrombolysis to treat DVT. We aim to further investigate the bubble-tissue interaction mechanism behind the histotripsy process. A deeper understanding of the interaction mechanism will provide a rational basis to optimize histotripsy acoustic parameters specific for thrombolysis. To reduce the embolization risk, we will develop a non-invasive embolus trap (NET) strategy by setting a secondary cavitating bubble cloud downstream of treatment location to capture and fractionate any escaping clot fragments. We will also develop real-time ultrasound imaging feedback techniques to guide and control the treatment progress and completion. These aims will be studied first in vitro and subsequently tested in an in vivo porcine venous thrombosis model. Successful completion of these specific aims will help us to develop a prototype histotripsy thrombolysis system to treat DVT in human patients, which could potentially lead to the broader application of histotripsy to other clinical conditions requiring thrombolysis, including stroke, superficial vein thrombosis, pulmonary embolism, and dialysis graft thrombosis. Public Health Relevance Statement (provided by applicant): Thrombosis is the medical term for the process of pathologic blood clot formation, the key mechanism behind many cardiovascular diseases. For example, deep vein thrombosis (DVT) is a condition which affects nearly two million Americans annually and is commonly diagnosed as clot formation in the deep veins of the legs. In up to 5% of DVT cases, clots dislodge and result in pulmonary embolism, causing at least 100,000 deaths annually in USA alone. To treat DVT, blood clots need to be removed, a process generally termed thrombolysis. Current clinical thrombolysis methods include thrombolytic drugs and catheter-based surgical procedure, both of which have significant drawbacks. For instance, thrombolytic drugs have the potential to cause excessive bleeding, which may be fatal in a small number of cases. Also, catheter-based procedures are invasive and carry risk of both bleeding and infection. We propose to develop an ultrasonic thrombolysis technique that is non-invasive and carries virtually no risks of bleeding and infection. Our first targeted clinical application will be DVT. In addition, we believe this technique could also potentially improve the standard of care for other clinical applications where thrombolysis is needed, including stroke, superficial vein thrombosis, dialysis graft thrombosis, bypass graft thrombosis or embolization, arterial embolism and pulmonary embolism.

描述（由申请人提供）：血栓形成是病理性血凝块形成过程的医学术语，是许多心血管疾病背后的关键机制。例如，深静脉血栓形成（DVT）是一种每年影响近200万美国人的疾病，通常被诊断为腿部深静脉血栓形成。为了治疗深静脉血栓，需要清除血凝块，这一过程通常被称为溶栓。目前的临床溶栓方法包括基于导管的程序和溶栓药物，这两种方法都有明显的缺点，包括侵入性和出血和感染的风险。为了提高溶栓的临床水平，我们建议发展一种无创、可携带的超声溶栓技术