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: 7690225
• 负责人: Zhen Xu
• 金额: $ 52.11万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7690225
• 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）：血栓形成是病理血凝块形成过程的医学术语，这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）是每年影响近200万美国人的疾病，通常被诊断为腿部深静脉中的血栓形成。为了治疗DVT，需要去除血凝块，这一过程通常称为溶栓。当前的临床溶栓方法包括基于导管的程序和溶栓药，这两种药物都有明显的缺点，包括侵入性和出血和感染的风险。为了提高溶栓的临床标准，我们建议开发一种非侵入性并携带的超声溶栓技术 几乎没有出血和感染的风险。我们称之为“组织疗法”的技术使用受控的超声气蚀来机械地分级软组织，并在高分辨率成像的指导下。通过使用适当的超声脉冲序列启动和维持空白的气泡云，可以通过受影响和正常组织之间非常狭窄的边界来精确地分馏靶组织。应用于溶栓，我们的初步数据表明，组织疗法可以比任何当前的临床溶栓方法快五十倍以五十倍的速度分离血凝块。组织疗法将血液凝块分解成小于红细胞小的微小颗粒。由于很容易检测到组织肌肉诱导的气泡，因此可以通过实时超声成像来指导和监测组织疗法的溶栓和监测。我们建议进一步改善和优化组织疗法，以进行安全有效的非侵入性溶栓以治疗DVT。我们旨在进一步研究组织摄氏过程背后的泡泡组织相互作用机制。对相互作用机制的更深入的了解将提供合理的基础，以优化针对溶栓特定的组织肌肉声学参数。为了降低栓塞风险，我们将通过将次要的cavitating cavitating气泡云设置为捕获 并分馏任何逃脱的凝块碎片。我们还将开发实时超声成像反馈技术，以指导和控制治疗的进度和完成。这些目标将首先在体外研究，然后在体内猪静脉血栓形成模型中进行测试。这些特定目标的成功完成将有助于我们开发一种原型的组织疗法溶栓系统，以治疗人类患者的DVT，这可能会导致组织疗法在其他需要血栓溶解的临床状况中更广泛地应用，包括中风，包括浅表静脉静脉血栓形成，肺栓塞，肺栓塞和透过糖尿病。 公共卫生相关性声明（由申请人提供）：血栓形成是病理血凝块形成过程的医学术语，这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）是每年影响近200万美国人的疾病，通常被诊断为腿部深静脉中的凝块形成。在多达5％的DVT病例中，凝块会脱落并导致肺栓塞，仅在美国，每年至少造成100,000人死亡。为了治疗DVT，需要去除血凝块，这是通常称为溶栓的过程。当前的临床溶栓方法包括溶栓药和基于导管的手术 过程，两者都有很大的缺点。例如，溶栓药物有可能引起过多的出血，这在少数情况下可能是致命的。此外，基于导管的程序具有侵入性，并具有出血和感染的风险。我们建议开发一种非侵入性的超声溶栓技术，几乎没有出血和感染的风险。我们的第一个目标临床应用将是DVT。此外，我们认为该技术还可以潜在地改善需要溶栓，浅表静脉血栓形成，透析移植血栓形成，旁路移植物或栓塞，动脉栓塞和肺栓塞的其他临床应用的护理标准。