Extracorporeal Lithotripsy Without Shock Waves

摘要/项目摘要 冲击波碎石术(SWL)是一种广泛使用的非侵入性手术，用于粉碎症状性肾结石， 在美国每年有30多万次治疗，尽管SWL作为一种非侵入性治疗很有吸引力 选择，重复治疗和/或辅助侵入性手术通常需要使患者 完全没有石头。事实上，SWL的成功率只有50%左右。除了相对较低的成功率之外 SWL可能会对肾脏和周围组织造成损害，后果严重。在……里面 项目2，我们基于对SWL中碎石机理的了解来设计一个相关的，但 完全不同的非侵入性治疗，可靠而安全地将结石粉碎成均匀的小碎片 是可以接受的，临床上无关紧要。这种新的冲击波碎石术(BWL)方法提供了几种- 无冲击的亚兆赫超声波周期脉冲串，使用的压力幅度明显低于 那些在SWL的人。170千赫换能器的初步研究表明，BWL破坏了人工和 天然结石(一水草酸钙、尿酸、鸟粪石、半胱氨酸)变成更均匀的小碎片 比SWL快，比临床SWL快。更高频率的平行研究表明，碎片大小是 由超声波频率控制。除了结石碎裂，初步的体内实验表明 使用BWL参数可以粉碎结石，几乎不会对猪肾脏造成伤害。最重要的是 这项工作的目的是促进BWL走向临床应用。BWL治疗的相关参数包括 超声频率和幅度、每个超声脉冲中的声周期数以及频率 在这一点上，发射出的脉冲。这项建议的前三个目标是寻求设计有效和安全的白线 具有这些参数的处理方案通过(1)测试最佳条件以有效地将结石粉碎成 容易通过(&lt；1 mm)碎片；(2)石材粉碎和建模的识别和建模机制 通过直接探查参数空间来改进程序；以及(3)评估 BWL治疗在猪模型上的体内实验损伤潜力。来自这三个方面的设计输入 AIMS，AIM(4)的目标是开发和测试临床前的BWL原型。建议进行的研究包括 与两个项目1的基于超声波的结石成像技术研究协同设计 以及声空化损伤的操作和项目3研究。这项工作将通过以下方式造福公众健康 为无创体外碎石(无冲击波)提供了一种新的策略，将导致 更快、更安全、更有效的临床治疗，改善了结石患者的预后。

ABSTRACT / PROJECT SUMMARY Shock wave lithotripsy (SWL) is a widely used noninvasive procedure to break symptomatic kidney stones, with more than 300,000 treatments annually in the U.S. Though SWL is appealing as a noninvasive treatment option, repeat treatments and/or ancillary invasive procedures are commonly required to render the patient entirely stone free. Indeed, SWL is successful in only about 50% of cases. In addition to relatively low success rates, SWL can cause injury to the kidney and surrounding tissues that can have serious consequences. In Project 2, we build on understanding of the mechanisms of stone fragmentation in SWL to design a related, but fundamentally distinct, noninvasive treatment to reliably and safely break stones into uniformly small fragments that are passable and clinically insignificant. This new burst wave lithotripsy (BWL) approach delivers several- cycle bursts of sub-megahertz ultrasound without shocks, using pressure amplitudes significantly lower than those in SWL. Preliminary studies with a 170 kHz transducer demonstrate that BWL breaks both artificial and natural stones (calcium oxalate monohydrate, uric acid, struvite, cystine) into more uniformly small fragments than SWL, faster than clinical SWL. Parallel studies at higher frequencies suggest that fragment sizes are controlled by the ultrasound frequency. Beyond stone fragmentation, initial in vivo experiments indicate that stones can be broken using BWL parameters that induce almost no injury in pig kidneys. The overarching objective of this effort is to advance BWL toward clinical use. Relevant parameters for BWL treatment include the ultrasound frequency and amplitude, the number of acoustic cycles in each ultrasound burst, and the rate at which bursts are delivered. The first three Aims of this proposal seek to design effective and safe BWL treatment protocols with these parameters by (1) testing for optimal conditions to efficiently break stones into easily passable (<1 mm) fragments; (2) identifying and modeling mechanisms for stone comminution and tissue injury to improve the procedure by direct exploration of the parameter space; and (3) evaluating the injury potential of BWL treatments with in vivo testing on the pig model. With design inputs from these three Aims, the goal of Aim (4) is to develop and test a pre-clinical BWL prototype. The proposed studies are designed synergistically with both the Project 1 studies on ultrasound-based technologies for stone imaging and manipulation and the Project 3 studies on acoustic cavitation injury. The work will benefit public health by providing a novel strategy for non-invasive extracorporeal lithotripsy (without shock waves) that will lead to faster, safer, more effective clinical treatments with improved outcomes for stone patients.