Control of Dynamically Coupled Cavitation Bubbles in Shock Wave Lithotripsy

描述（由申请人提供）体外冲击波碎石术（SWL）是用于粉碎尿路结石的最广泛使用的手术，但经过20年的SWL，安全性和有效性似乎在下降，而不是提高。在一些报告中，肾脏内具有临床意义的肿瘤增加了10倍，成功治疗的可能性减少了一半。对公众健康的影响是风险/效益比和重复治疗的成本增加。体外和体内实验已经表明，空化在期望的效果（结石粉碎）和不期望的副作用（组织损伤）中起重要作用，并且尽管在粉碎中需要一些不确定数量的气泡，但是可以由高冲击波输送速率产生的更多气泡抑制粉碎。最近的高速摄像机图像表明，空化气泡簇可以增长到包裹结石，并且现有的单个孤立气泡理论无法预测簇动力学。目前SWL中没有模型考虑气泡彼此或与附近组织的动态耦合。该项目的目标及其与公共卫生的相关性是开发准确的分析模型，通过实验进行测试和支持，以增加我们对肾结石和组织附近空化簇的理解，并为提高SWL的有效性和安全性提供指导。该项目有三个具体目标。(1)开发气泡簇动力学的数学模型，并使用该模型来理解和预测与簇中单个空化气泡相关的生长、平移、崩溃和冲击波辐射，并估计这些效应对结石的集体影响。扩展模型以考虑散布在气泡中的固体颗粒。计算并比较由集群产生的压力和由四台临床碎石机产生的冲击波。最终，确定参数并预测冲击波波形、冲击波输送速率和碎石机射束宽度的条件，以改善结石粉碎。(2)开发一个模型，用于在肾小管、血管和其他由组织限定的空间中的单个和簇状气泡动力学。(3)使用压电传感器和两个高速摄像机获得集群内的压力测量值和集群动态的3D电影，以与模型模拟进行比较。通过数值和实验量化结石或血管壁上的压力，作为气泡数量的影响，从而确定SW输送速率。同时，在B型超声上表征抑制簇，作为对临床医生的反馈。总之，模型和实验结果可以指导监测，协议和碎石机的发展。

DESCRIPTION (provided by applicant) Extracorporeal shock wave lithotripsy (SWL) is the most widely used procedure for comminution of urinary tract calculi, but after two decades of SWL, safety and efficiency appear to be declining, not improving. In some reports, clinically significant hemorrhaging within the kidney has increased tenfold, and the probability of successful treatment has been reduced by half. The effect on public health has been an increased risk/benefit ratio and cost of repeated treatments. In vitro and in vivo experimentation have shown that cavitation plays an important role in both the desired effect, stone comminution, and the undesired side effect, tissue injury, and that whereas some undefined number of bubbles is necessary in comminution, more bubbles, as can be produced by high shock wave delivery rates, inhibit comminution. Recent high-speed camera images indicate that the cavitation bubble cluster can grow to envelop the stone and that the cluster dynamics cannot be predicted by existing theories for single, isolated bubbles. Currently no model in SWL accounts for the dynamic coupling of bubbles to one another or to nearby tissue. The goal of this project and its relevance to public health is to develop accurate analytical models, tested and supported by experiment, to increase our understanding of cavitation clusters near kidney stones and tissue, and to provide guidance for improving the efficacy and safety of SWL. The project has three specific aims. (1) Develop a mathematical model for bubble cluster dynamics and use this model to understand and predict the growth, translation, collapse, and shock wave radiation associated with individual cavitation bubbles in the cluster, and to estimate the collective impact of these effects on the stone. Expand the model to account for solid particles interspersed among the bubbles. Calculate and compare pressures produced by the cluster and the shock wave produced by four clinical lithotripters. Ultimately, determine parameters and predict conditions for shock waveform, shock wave delivery rate, and lithotripter beam width that improve stone comminution. (2) Develop a model for individual and clustered bubble dynamics in urinary tubules, blood vessels, and other spaces confined by tissue. (3) Obtain pressure measurements within the cluster and 3D movies of cluster dynamics using piezoelectric sensors and two high speed cameras to compare to model simulations. Quantify numerically and experimentally the pressure on a stone or vessel wall as an effect of bubble number and therefore SW delivery rate. Simultaneously, characterize inhibitory clusters on B-mode ultrasound as a feedback to clinicians. Together, the model and experimental results may then guide monitoring, protocol, and lithotripter development.