Development of a Novel Gas Embolotherapy Technique

描述（由申请人提供）： 将栓塞物递送至动脉血流以实现血流阻断或栓塞治疗，是治疗多种癌症的潜在手段，例如肝细胞癌（HCC）和肾癌。HCC是最常见的肝癌形式，每年每100，000名男性中有2-30人发生，每年导致全球约1，250，000人死亡。伴随的肝硬化使得通过传统方法治疗HCC变得困难。全身化疗对生存率无明显影响。除了这些类型的癌症之外，许多其他类型的癌症也可以使用放射疗法进行治疗。先前的栓塞治疗尝试使用固体栓塞物，例如血凝块、明胶海绵、颗粒、球囊和飘带。栓塞治疗的主要困难是限制栓塞物向肿瘤的递送，即在没有极端侵入性手术的情况下使健康组织的缺血最小化。 在这里，我们提出了一种声激活气体栓塞疗法。虽然气泡已被用作超声造影剂，但它们以前未被用于阻塞流向肿瘤的血流。此外，这种新颖的方法涉及将小到足以穿过毛细血管的液滴引入血管流中。可以使用超声跟踪液滴，并通过肿瘤附近的高强度超声蒸发，从而允许气泡（其比它们起源的液滴大得多）阻塞肿瘤中的流动。这种微创技术将允许选择性地将气体栓塞输送到肿瘤，并且非常适合重复剂量和长期使用。拟议的研究使用计算和实验（动物和实验台）研究，以提供这种技术的概念证明。本研究将探讨气体栓塞造成血管阻塞的物理现象，以及液滴汽化造成血管变形的现象。拟议的研究是工程师，物理学家和临床医生在流体动力学，气体输送，诊断和治疗超声方面的专业知识的合作。这项研究是开发这项潜在革命性技术的重要第一步。

DESCRIPTION (provided by applicant): The delivery of emboli to arterial blood flow with the goal of flow occlusion, or embolotherapy, is a potential means to treat a variety of cancers, such as heptatocellular carcinoma (HCC) and renal carcinoma. HCC, the most common form of liver cancer, occurs in 2-30 per 100,000 males each year, resulting in approximately 1,250,000 deaths worldwide annually. The accompanying liver cirrhosis makes the treatment of HCC by traditional methods difficult. Systemic chemotherapy has no appreciable impact on survival rates. In addition to these types of cancer, many other types could potentially be treated using embototherapy. 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. Here, we propose an acoustically activated gas embolotherapy. While gas bubbles have been used as ultrasonic contrast agents, they have not previously been used to occlude flow to tumors. Moreover, this novel approach involves introducing liquid droplets, which are small enough to pass through capillaries, into the vascular flow. The droplets could be tracked using ultrasound and vaporized via high intensity ultrasound near the tumor allowing gas bubbles, which are considerably larger than the liquid drops from which they originated, to occlude flow in the tumor. This minimally invasive technique would allow selective delivery of gas emboli to the tumor, and is well suited to repeated doses and long term use. The proposed research uses computational and experimental (animal and bench top) studies to provide proof of concept of this technique. This work will investigate the physical phenomena of vessel occlusion by gas emboli and vessel deformation due to the vaporization of liquid droplets. The proposed research is a collaboration of engineers, physicists, and clinicians with expertise in expertise in fluid dynamics, gas transport, and diagnostic and therapeutic ultrasound. The proposed research is an essential first step in developing this potentially revolutionary technique.