Burst Wave Lithotripsy for the Treatment of Ureteral Calculi

 描述(由申请人提供)：意义：尿路结石造成了巨大的医疗负担，每年给美国带来的成本超过100亿美元。随着糖尿病和肥胖症等风险因素变得更加普遍，结石病对医疗体系的影响预计将继续增长。尤其是输尿管结石，通常是有症状的，而且结石的大小和位置对自然排出有很大影响，因此输尿管结石的处理尤其困难。警惕等待结合驱逐治疗是一线方法，但可能导致重复内科和/或急诊科就诊，丧失生产力，并给患者带来压力。对于积极干预，体外冲击波碎石术(SWL)通常需要重复或二次操作才能达到无结石状态。输尿管镜检查是一种微创手术，与SWL相比，结石排净率更高，但并发症发生率更高。技术：冲击波碎石术(BWL)是一种新的、非侵入性的碎石方法，有可能显著改善输尿管结石的治疗。BWL使用多周期、低幅度的超声波脉冲而不是冲击波来非侵入性地诱导结石骨折。这种方法有可能减少受伤、程序并发症和额外程序的风险，并显著减少程序时间和成本。此外，使用的低脉压幅度可能会排除麻醉的需要，为警惕等待提供了一个有吸引力的替代方案。初步数据：体外研究表明，这项技术能够打破人类发现的所有常见类型的结石。结果还表明，碎片的大小可以通过改变超声频率来控制，以产生可能自发通过而没有进一步症状的小碎片。初步研究表明，在一项猪动物研究中，碎石所需的压力水平明显低于导致肾脏损伤所需的压力水平。具体目标：这是一个快速通道提案，将使用第一阶段来解决技术问题，即与水浴中的结石相比，应该如何改变BWL参数来治疗输尿管内梗阻的结石。这将需要组装BWL换能器和放大器(第一阶段目标1)，并进行体外研究，以确定在输尿管体模内粉碎结石所需的压力水平和剂量(时间)(第一阶段目标2)。第二阶段确定定位输尿管结石时暴露的声学窗口和关键结构(第二阶段目标1)，并设计专门用于这些窗口的商业原型换能器，并操作第一阶段(第二阶段目标2)确定的声学参数。BWL系统将由具有专门算法的超声成像系统引导，以增强目标定位和检测空化，以监测和控制损伤(第二阶段目标3)。开发的系统的安全性和有效性将在猪动物模型中进行测试(第二阶段目标为4，5)。

 DESCRIPTION (provided by applicant): Significance: Urinary tract stones pose a significant healthcare burden, with costs to the US exceeding $10 billion annually. The impact of stone disease on the healthcare system is expected to continue to grow as risk factors such as diabetes and obesity become more prevalent. Ureteral stones in particular pose a management challenge as they are often symptomatic, and spontaneous passage is a strong function of stone size and location. Watchful waiting in combination with expulsion therapy is the first line approach, but can lead to repeat physician and/or emergency department visits, lost productivity, and stress on the patient. For active intervention, extracorporeal shock wave lithotripsy (SWL) often requires repeat or secondary procedures to achieve stone-free status. Ureteroscopy, a minimally invasive procedure, has greater stone free rates than SWL, but higher complication rates. Technology: Burst wave lithotripsy (BWL) is a novel, noninvasive, method of stone fragmentation that has the potential to significantly improve the management of ureteral stones. BWL uses multi-cycle, low-amplitude pulses of ultrasound rather than shock waves to noninvasively induce stone fracture. This approach has the potential to reduce the risk of injury, procedural complications, and additional procedures, as well as result in a significant reduction in procedural time and cost. Furthermore, the low pulse pressure amplitude used may preclude the need for anesthesia, providing an attractive alternative to watchful waiting. Preliminary Data: In-vitro studies have shown the technology is capable of breaking all common types of stones found in humans. Results also show that the fragment size can be controlled by altering the ultrasound frequency to produce small fragments likely to spontaneously pass without further symptoms. Preliminary studies indicate the pressure levels required to break stones are significantly below the pressure levels required to induce renal injury in a porcine animal study. Specific Aims: This is a fast-track proposal that will use Phase I to address the technical question of how BWL parameters should be altered to treat a stone obstructed within a ureter compared to a stone free in a water bath. This will require assembly of a BWL transducer and amplifier (Phase I Aim 1) and in vitro studies to establish the pressure level and dose (time) required to break stones within a ureteral phantom (Phase I Aim 2). Phase II identifies the acoustic windows and critical structures exposed while targeting ureteral stones (Phase II Aim 1) and designs the commercial prototype transducer specific for those windows and operating the acoustic parameters identified in Phase I (Phase II Aim 2). The BWL system will be guided by an ultrasound imaging system with specialized algorithms to enhance targeting and detect cavitation to monitor and control for injury (Phase II Aim 3). The safety and efficacy of the developed system will be tested in a porcine animal model (Phase II Aims 4, 5).