Harnessing cavitation using a tubular transducer geometry for catheter based applications

大血管阻塞是导致死亡和残疾的主要原因。这些包括急性（软）血凝块在冠状动脉、大脑或外周血管中的倒伏，以及更复杂的长期闭塞（慢性全闭塞），其上游可能有僵硬的“帽”。因此，解决血管闭塞以恢复血液流动是临床的一个高度优先事项，但在许多情况下，目前的方法很难解决。标准护理方法包括药物治疗（如静脉注射药物）、手术（如冠状动脉搭桥）和导管程序（如取出血栓或放置支架）。“治疗性”超声也在研究中，以疏通闭塞。这包括一系列的方法，其中许多涉及到用超声波诱导微米级循环气泡的振动（“空化”）。我们最近提出并原型化了一种新颖的设计概念，用于基于正向导管的超声，其中包括位于其尖端的管状换能器（超声源）。这带来了许多独特的优势。从本质上讲，它可以通过导线直接引导到闭塞处，通过导管和换能器孔注入气泡和药物，然后用超声波精确地暴露在目标部位。有了这种新的方法和它的几何形状，也有许多未探索的物理考虑提供超声闭塞。本研究计划的目的是调查这种情况下空化的基本方面，以便为制定暴露方案提供合理的基础。在这个程序中有两个流。首先，我们将检查试管内的气泡如何表现，超声波如何将它们推出试管，以及如何适当地“爆裂”它们以打破闭塞。这些效应将是光束空间模式的函数，而空间模式又与试管的长度和所使用的超声波频率有关。这将通过计算机模拟、测量压力和使用高速显微镜来观察气泡的行为来实现。这项工作与现有临床批准的气泡何时通过导管尖端注射有关。在第二流中，我们将研究如何在超声导管尖端实际产生气泡。这将使用非常小的“液滴”——小于一微米的大小，以及一种简单的脂质溶液来稳定管内产生的任何气泡。由此产生的气泡可以用于治疗，而不需要外部注射气泡。总之，这项工作将提供知识基础，使这种新方法能够得到优化。优化系统的最终结果将是一种影响很大一部分慢性全闭塞（20%）冠心病患者以及其他大血管血栓患者治疗的方法。

The occlusion of large blood vessels is a leading cause of death and disability. These include the acute lodging of (soft) blood clots in coronary, brain or peripheral vessels as well as more complex longer term occlusions (chronic total occlusions) which can have a stiff upstream `caps'. Resolving vascular occlusions to restore blood flow is therefore a high clinical priority, but is in many circumstances poorly addressed by current methods. Standard of care approaches include medical therapy (e.g. intravenously injecting drugs), surgery (e.g. coronary bypass) and catheter procedures (e.g. to retrieve clot or place a stent). `Therapeutic' ultrasound is also under investigation to unblock occlusions. This encompasses a range of methods, many of which involve inducing vibrations (`cavitation') of micron sized circulating bubbles with the ultrasound. We have recently proposed and prototyped a novel design concept for forward directed catheter based ultrasound that involves a tubular transducer (ultrasound source) situated at its tip. This presents a number of unique advantages. Essentially it can be guided over a wire right up to the occlusion, inject the bubbles and drugs through the catheter and transducer hole then expose with ultrasound precisely at the target site. With this new approach and its geometry, there are also many unexplored physical considerations for delivering ultrasound to occlusions. This research program has the objective of investigating basis aspects of cavitation for this situation in order to provide a rational basis for developing exposure protocols. There are two Streams within this program. First, we will examine how bubbles behave within the tube, how the ultrasound can push them out of the tube, and how to `burst' them appropriately to break up the occlusion. These effects will be a function of the spatial pattern of the beam, which is in turn a function of the length of the tube and the frequency of ultrasound that is used. This will be approached with computer simulations, measuring the pressures and using a very high speed microscope to look at the bubble behaviour. This work is relevant to when existing clinically approved bubbles are injected through the catheter tip. In the second Stream, we will investigate how to actually generate bubbles within the tip of the catheter with the ultrasound. This will be done using very small `droplets'- less than a micron in size, as well as a simple solution of lipids which will stabilize any bubbles generated within the tube. The resulting bubbles can then be used for therapy without externally injected bubbles. Together this work will provide the foundation of knowledge that will enable this new approach to be optimized. The end result of the optimized system will be a method to impact the treatment of a significant portion of patients with coronary disease that have chronic total occlusions (20%), as well as other patients that have blood clots in large vessels.