Dynamics of Vascular Microbubbles and Microdroplets in Gas Embolotherapy

气体栓塞治疗中血管微泡和微滴的动力学

• 批准号: 7496105
• 负责人: JOSEPH L BULL
• 金额: $ 39.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496105
• 关键词: Acoustics; Address; Albumins; Area; Blood Circulation; Blood Clot; Blood Vessels; Blood capillaries; Blood coagulation; Blood flow; Caliber; Cardiovascular system; Clinic; Clinical; Diagnostic; Disease; Dose; Drug Delivery Systems; Embolism; Encapsulated; Excision; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Fibroid Tumor; Fluorocarbons; Foundations; Gases; Gelatin; Goals; Grant; In Vitro; Injection of therapeutic agent; Invasive; Ischemia; Knowledge; Left; Liquid substance; Localized; Location; Malignant Neoplasms; Malignant neoplasm of liver; Mechanics; Methodology; Methods; Microbubbles; Microcirculation; Modality; Modeling; Necrosis; Paper; Particulate; Personal Satisfaction; Placement; Porifera; Preparation; Primary carcinoma of the liver cells; Procedures; Process; Production; Public Health; Publishing; Renal carcinoma; Research; Rupture; Saline; Shapes; Solid; Source; Staging; Survival Rate; Techniques; Therapeutic Embolization; Time; Tissues; Translations; Ultrasonography; Uterine Fibroids; Vascular System; Venous; Work; cancer therapy; capillary; capillary bed; chemotherapy; concept; fundamental research; in vivo; intravital microscopy; novel; research study; tumor; vaporization

DESCRIPTION (provided by applicant): Embolotherapy involves the occlusion of blood flow for therapy. This type of approach has primarily been used for treating a variety of cancers by starving tumors of blood flow, and for treating uterine fibroids. One example of a cancer that is well suited to treatment by embolotherapy is hepatocellular carcinoma, the most common form of liver cancer. Systemic chemotherapy has no appreciable impact on survival rates. Previous attempts at embolotherapy have used solid emboli, such as blood clot, gelatin sponge, particulates, balloons and streamers. A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor, i.e. minimizing ischemia of healthy tissue, without extremely invasive procedures. The novelty of our gas embolotherapy approach lies in the use of gas bubbles rather than solid emboli. The bubbles originate as encapsulated liquid droplets that can be vaporized in vivo by focused high intensity ultrasound to form gas bubbles which then lodge in the tumor vasculature. This minimally invasive technique would allow selective delivery of gas emboli to the target region, and is well suited to repeated doses and long term use. Droplets small enough to pass through capillaries would allow venous injection. Our preliminary work suggests the potential of this treatment modality for many applications, yet many questions remain regarding delivery of droplets/bubbles and their interaction with vessels and blood. The proposed research will experimentally and computationally investigate the dynamics of vascular bubbles and droplets to provide new knowledge that is essential to developing this potentially revolutionary treatment. The specific aims of this proposal are: 1. Characterize the process of acoustic droplet vaporization (ADV), including the mechanisms involved and the effects of droplet and flow parameters. 2. Evaluate the processes by which by the resulting bubbles are transported through the vasculature prior to lodging, and evaluate the effects of bubble and flow parameters on the ability to target specific locations for bubble delivery. 3. Assess the dynamics of bubble lodging and the ability of lodged bubbles to occlude blood flow. This work is relevant to public health by providing a fundamental understanding of how to use the controlled formation of cardiovascular gas bubbles, which originate from liquid droplets, to locally occlude blood flow for therapy. This approach could potentially be used to treat a variety of cancers and uterine fibroids.

描述（由申请人提供）：栓塞疗法涉及治疗的血液流动。这种类型的方法主要用于通过饥饿的血流肿瘤和子宫肌瘤来治疗多种癌症。肝癌是肝癌，这是肝癌最常见的肝癌的一个例子是肝癌。全身化疗对生存率没有明显的影响。先前对栓塞疗法的尝试使用了固体栓子，例如血凝块，明胶海绵，颗粒，气球和彩带。栓塞疗法的主要困难是将栓子递送到肿瘤，即在没有极为侵入性手术的情况下最大程度地减少健康组织缺血。我们的气体疗法方法的新颖性在于使用气泡而不是固体栓子。气泡起源于封装的液滴，可以通过聚焦的高强度超声在体内蒸发以形成气泡，然后在肿瘤脉管系统中产生气泡。这种微创技术将允许选择性递送气体栓塞到目标区域，并且非常适合重复剂量和长期使用。足够小的液滴可以通过毛细血管可以静脉注射。我们的初步工作表明了这种治疗方式对许多应用的潜力，但是关于液滴/气泡的交付及其与血管和血液的相互作用仍然存在许多问题。拟议的研究将在实验和计算上研究血管气泡和液滴的动力学，以提供新知识，这对于开发这种潜在革命性的治疗至关重要。该提案的具体目的是：1。表征声学液滴汽化的过程（ADV），包括所涉及的机制以及液滴和流参数的影响。 2。评估在住宿前通过脉管系统通过脉管系统运输的过程，并评估气泡和流参数对靶向特定位置以进行气泡输送的能力的影响。 3。评估气泡住宿的动力学以及储藏气泡阻塞血流的能力。这项工作与公共卫生有关，通过对如何使用源自液滴的心血管气泡的受控形成的基本理解，以便在局部阻塞血液以进行治疗。这种方法可能可用于治疗各种癌症和子宫肌瘤。