Dynamics of Vascular Microbubbles and Microdroplets in Gas Embolotherapy

描述(申请人提供)：栓塞术包括阻断血流以进行治疗。这种方法主要用于通过阻断肿瘤的血流来治疗各种癌症，以及治疗子宫肌瘤。肝细胞癌是最常见的一种肝癌，非常适合通过栓塞术进行治疗。全身化疗对存活率没有明显影响。以前的栓塞术尝试使用固体栓子，如血块、明胶海绵、微粒、气球和彩带。栓塞术的一个主要困难是限制栓子向肿瘤的输送，即在不进行极具侵入性的操作的情况下将健康组织的缺血降至最低。我们的气体栓塞术的创新之处在于使用了气泡而不是固体栓子。这些气泡起源于被包裹的液滴，可以通过聚焦的高强度超声波在体内蒸发，形成气泡，然后停留在肿瘤血管中。这种微创技术将允许选择性地将气体栓子输送到靶区，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进行静脉注射。我们的初步工作表明，这种治疗方式具有许多应用的潜力，但关于液滴/气泡的输送及其与血管和血液的相互作用仍存在许多问题。这项拟议的研究将通过实验和计算来研究血管气泡和液滴的动力学，以提供对开发这种潜在的革命性治疗方法至关重要的新知识。该方案的具体目的是：1.描述声学液滴蒸发(ADV)过程，包括涉及的机理以及液滴和流动参数的影响。2.评估所产生的气泡在倒伏前通过血管系统传输的过程，并评估气泡和流动参数对将气泡输送到特定位置的能力的影响。3.评估气泡滞留的动力学和滞留的气泡堵塞血流的能力。这项工作与公众健康相关，因为它提供了一个基本的理解，即如何利用源自液滴的心血管气泡的受控形成来局部阻断血流以进行治疗。这种方法可能被用于治疗各种癌症和子宫肌瘤。

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.