Dynamics of Vascular Microbubbles and Microdroplets in Gas Embolotherapy

描述（由申请人提供）：栓塞疗法涉及阻断血流进行治疗。这种方法主要用于通过抑制肿瘤血流来治疗多种癌症，以及治疗子宫肌瘤。非常适合通过栓塞疗法治疗的癌症的一个例子是肝细胞癌，这是最常见的肝癌形式。全身化疗对生存率没有明显影响。先前的栓塞治疗尝试使用了固体栓塞，例如血凝块、明胶海绵、颗粒、气球和飘带。栓塞治疗的一个主要困难是限制栓子向肿瘤的输送，即最大限度地减少健康组织的缺血，而不需要极度侵入性的手术。我们的气体栓塞治疗方法的新颖之处在于使用气泡而不是固体栓塞。这些气泡起源于封装的液滴，可以通过聚焦高强度超声波在体内汽化，形成气泡，然后滞留在肿瘤脉管系统中。这种微创技术可以选择性地将气体栓塞输送到目标区域，并且非常适合重复剂量和长期使用。小到足以穿过毛细血管的液滴将允许静脉注射。我们的初步工作表明这种治疗方式在许多应用中具有潜力，但关于液滴/气泡的输送及其与血管和血液的相互作用仍然存在许多问题。拟议的研究将通过实验和计算研究血管气泡和液滴的动力学，以提供对于开发这种潜在的革命性治疗至关重要的新知识。该提案的具体目标是： 1. 表征声学液滴汽化（ADV）的过程，包括所涉及的机制以及液滴和流动参数的影响。 2.评估所产生的气泡在倒伏之前通过脉管系统运输的过程，并评估气泡和流动参数对气泡递送的目标特定位置的能力的影响。 3. 评估气泡滞留的动态以及滞留的气泡阻塞血流的能力。这项工作与公共卫生相关，它提供了对如何利用源自液滴的心血管气泡的受控形成来局部阻塞血流进行治疗的基本了解。这种方法有可能用于治疗多种癌症和子宫肌瘤。

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.