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

基本信息

  • 批准号:
    7899949
  • 负责人:
  • 金额:
    $ 48.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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 (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。为了治疗 DVT,需要清除血栓,这个过程通常称为溶栓。目前临床溶栓方法包括导管溶栓和溶栓药物,两者都存在显着的缺点,包括侵入性以及出血和感染的风险。为提高溶栓临床水平,我们建议开发一种无创、携带方便的超声溶栓技术。 几乎没有出血和感染的风险。我们的技术称为“组织解剖术”,在高分辨率成像的引导下,利用受控超声空化以非侵入性方式机械分割软组织。通过用适当的超声脉冲序列启动和维持空化气泡云,可以精确地分割目标组织,受影响组织和正常组织之间的边界非常窄。当应用于溶栓时,我们的初步数据表明,组织解剖学可以以比目前任何临床溶栓方法快五十倍的速度分割血块。组织解剖学将血凝块分解成比红细胞更小的微小颗粒。由于组织解剖引起的空泡很容易通过声学检测到,因此可以通过实时超声成像来指导和监测组织解剖溶栓。我们建议进一步改进和优化组织解剖学,以实现安全有效的无创溶栓治疗 DVT。我们的目标是进一步研究组织解剖过程背后的气泡-组织相互作用机制。更深入地了解相互作用机制将为优化溶栓特异性组织解剖声学参数提供合理基础。为了降低栓塞风险,我们将开发一种非侵入性栓塞陷阱(NET)策略,通过在治疗位置下游设置二次空化气泡云来捕获 并分级任何逸出的凝块碎片。我们还将开发实时超声成像反馈技术来指导和控制治疗进展和完成。这些目标将首先在体外进行研究,然后在体内猪静脉血栓形成模型中进行测试。成功完成这些具体目标将有助于我们开发原型组织解剖溶栓系统来治疗人类患者的 DVT,这可能会导致组织解剖学更广泛地应用于其他需要溶栓的临床疾病,包括中风、浅静脉血栓形成、肺栓塞、和透析移植物血栓形成。 公共卫生相关性声明(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 (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中形成血栓。在高达 5% 的 DVT 病例中,血栓脱落并导致肺栓塞,仅在美国每年就造成至少 100,000 人死亡。为了治疗 DVT,需要清除血块,这个过程通常称为溶栓。目前临床溶栓方法包括溶栓药物和导管手术 程序,两者都有显着的缺点。例如,溶栓药物有可能导致过度出血,在少数情况下可能致命。此外,基于导管的手术是侵入性的,存在出血和感染的风险。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。我们的第一个有针对性的临床应用将是DVT。此外,我们相信这项技术还有可能提高其他需要溶栓的临床应用的护理标准,包括中风、浅静脉血栓、透析移植血栓、旁路移植血栓或栓塞、动脉栓塞和肺栓塞。

项目成果

期刊论文数量(0)
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Zhen Xu其他文献

Zhen Xu的其他文献

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{{ truncateString('Zhen Xu', 18)}}的其他基金

Ultrasound-guided Ultra-steerable Histotripsy Array System for Non-invasive treatment of Soft Tissue Sarcoma
超声引导超可控组织解剖阵列系统用于软组织肉瘤的无创治疗
  • 批准号:
    10649994
  • 财政年份:
    2023
  • 资助金额:
    $ 48.48万
  • 项目类别:
The Role of Podosomes in Cerebrovascular Integrity and Intracranial Aneurysm
足体在脑血管完整性和颅内动脉瘤中的作用
  • 批准号:
    10586672
  • 财政年份:
    2023
  • 资助金额:
    $ 48.48万
  • 项目类别:
Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)
经颅磁共振引导组织解剖 (tcMRgHt)
  • 批准号:
    10396108
  • 财政年份:
    2019
  • 资助金额:
    $ 48.48万
  • 项目类别:
Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)
经颅磁共振引导组织解剖 (tcMRgHt)
  • 批准号:
    10183248
  • 财政年份:
    2019
  • 资助金额:
    $ 48.48万
  • 项目类别:
Novel, Noninvasive, Rapid Tumor Ablation Technology using Histotripsy
使用组织解剖学的新型、无创、快速肿瘤消融技术
  • 批准号:
    10322649
  • 财政年份:
    2018
  • 资助金额:
    $ 48.48万
  • 项目类别:
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:
    7559042
  • 财政年份:
    2008
  • 资助金额:
    $ 48.48万
  • 项目类别:
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
  • 财政年份:
    2008
  • 资助金额:
    $ 48.48万
  • 项目类别:
Image-guided Non-invasive Ultrasonic Thrombolysis Using Histotripsy
使用组织解剖学进行图像引导的无创超声溶栓
  • 批准号:
    8875679
  • 财政年份:
    2008
  • 资助金额:
    $ 48.48万
  • 项目类别:
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
  • 财政年份:
    2008
  • 资助金额:
    $ 48.48万
  • 项目类别:
Image-guided Non-invasive Ultrasonic Thrombolysis Using Histotripsy
使用组织解剖学进行图像引导的无创超声溶栓
  • 批准号:
    8755293
  • 财政年份:
    2008
  • 资助金额:
    $ 48.48万
  • 项目类别:

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