Extracorporeal Lithotripsy Without Shock Waves

摘要/项目总结 冲击波碎石术（SWL）是一种广泛使用的非侵入性手术，用于破碎有症状的肾结石， 尽管SWL作为一种非侵入性治疗很有吸引力， 选择，通常需要重复治疗和/或辅助侵入性程序来使患者 完全没有石头。事实上，SWL在大约50%的情况下是成功的。除了相对较低的成功率外， 如果发生率较高，SWL可能会对肾脏和周围组织造成损伤，从而导致严重后果。在 项目2，我们基于对SWL中结石破碎机制的理解，设计了一个相关的，但 从根本上独特的非侵入性治疗，可靠安全地将结石破碎成均匀的小碎片 可以接受的临床上无意义的治疗这种新的爆破波碎石术（BWL）方法提供了几个- 亚兆赫超声波的周期脉冲，无冲击，使用的压力幅度明显低于 那些在SWL。使用170 kHz换能器的初步研究表明，BWL会破坏人工和 天然结石（一水草酸钙、尿酸、鸟粪石、胱氨酸）粉碎成更均匀的小碎片 比SWL更快，比临床SWL更快。在更高频率下的平行研究表明， 由超声波频率控制。除了结石破碎，最初的体内实验表明， 可以使用在猪肾中几乎不引起损伤的BWL参数来破碎结石。总体 这一努力的目的是将BWL推向临床应用。BWL治疗的相关参数包括 超声频率和振幅、每个超声脉冲群中的声周期数以及超声脉冲群的速率 在其上传送突发。本提案的前三个目标旨在设计有效和安全的BWL （1）测试最佳条件以有效地将结石破碎成 容易通过的碎片（<1 mm）;（2）识别和建模结石粉碎的机制， 组织损伤，以通过参数空间的直接探索来改进程序;以及（3）评估 通过在猪模型上的体内测试来评估BWL治疗的损伤潜力。从这三个设计输入 目的，目的（4）的目标是开发和测试临床前BWL原型。拟议的研究是 与基于超声的结石成像技术的项目1研究协同设计 和操作以及项目3关于声空化损伤的研究。这项工作将有利于公众健康， 为非侵入性体外碎石术（无冲击波）提供了一种新的策略， 更快、更安全、更有效的临床治疗，改善结石患者的预后。

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.