Strategies to Maximize Burst Wave Lithotripsy (BWL) Success

项目摘要/摘要--项目2 肾结石疾病影响着大约11%的美国人，并给美国人带来巨大的经济负担 医疗保健系统。最常见的治疗方法是冲击波碎石术(SWL)和输尿管镜检查(URS)， 它使用非侵入性或微创性的技术来粉碎结石，这样小碎片要么通过 自然的或可以去除的。尽管这些方法比开放手术提供了显著的改进， 它们通常需要重新治疗，可能会对肾脏或输尿管造成损伤，并需要大量的资源 作为手术套间和麻醉剂。为了解决这些限制，冲击波碎石术(BWL)可以提供一种 有效的、安全的、办公室内治疗方法，供泌尿科医生碎石。BWL是一种新的非侵入性手术方式 该技术目前正在进行临床试验。BWL治疗可以由一个小系统提供，即 易于与其他超声波技术集成，以进行结石成像和推石。BWL使用短脉冲 亚兆赫超声波将石头粉碎成均匀的碎片，并已被证明可以可靠地粉碎 许多类型的天然结石暴露，对猪肾脏的损伤很小，如果有的话。作为BWL 继续向临床应用迈进，与个体患者之间的变异性相关的挑战应该是 旨在最大限度地取得特定治疗的成功，并扩大可治疗疾病的范围。为 目前实施的BWL，在体内的可变性已经观察到在空化行为的开始 可能会导致结石的损伤和屏蔽，使其无法得到有效的治疗。因为治疗监测与 超声(US)成像已被证明能够实时检测伤害性空化活动的开始， 自适应地选择和修改BWL治疗参数的潜力是显而易见的。这项建议的第一个目的是 包括一系列体外和体内实验，以了解结石如何影响空化并与 根据超声成像和带有碎裂的后向散射得出的空化度量。这些数据将得到补充 通过来自Aim 3的模拟，使用经过验证的空化数值模型在石块附近发展 调整治疗参数的策略。本提案的目标2和3侧重于理解和 利用结石骨折的机制开发先进的BWL治疗策略。目标2涉及 在空间和时间上操纵BWL暴露以改进的策略的实验测试 碎片化。Aim 3利用数值模拟工具识别不同岩石的断裂力学 几何和信息策略，以诱导和检测其他目标的骨折。建议进行的研究包括 与项目1和项目3中的临床试验协同设计，研究结石成像和操作 项目1，以及项目3中的BWL相关伤害研究。这项工作将通过改善 BWL作为结石患者的非侵入性替代方案的成功。

PROJECT SUMMARY / ABSTRACT – Project 2 Kidney stone disease affects about 1 in 11 Americans and imposes a significant economic burden on the healthcare system. The most common treatments are shock wave lithotripsy (SWL) and ureteroscopy (URS), which use noninvasive or minimally invasive techniques to break stones so that small fragments either pass naturally or can be removed. Although these approaches provide significant improvements over open surgery, they often involve retreatment, can cause injury to the kidney or ureter, and require significant resources such as a surgical suite and anesthetics. To address these limitations, burst wave lithotripsy (BWL) may provide an effective, safe, in-office treatment approach for a urologist to break stones. BWL is a new noninvasive approach that is currently in development toward clinical trials. BWL treatments can be delivered by a small system that is readily integrated with other ultrasound technologies for stone imaging and pushing. BWL uses short bursts of sub-megahertz ultrasound to break stones into uniform fragments and has been demonstrated to reliably break many types of natural stones with exposures that produce little, if any, injury in porcine kidneys. As BWL continues to advance toward clinical use, challenges related to variability among individual patients should be addressed to maximize the success of a given treatment and to expand the range of treatable conditions. For current implementations of BWL, variability in vivo has been observed in the onset of cavitation behaviors that may lead to both injury and shielding of the stone from effective treatment. Because treatment monitoring with ultrasound (US) imaging has been shown to enable real-time detection of the onset of injurious cavitation activity, the potential to adaptively select and modify BWL treatment parameters is apparent. The first Aim of this proposal comprises a series of in vitro and in vivo experiments to understand how stones affect cavitation and to correlate cavitation metrics derived from US imaging and backscatter with fragmentation. These data will be supplemented by simulations from Aim 3 with a validated numerical model of cavitation in the vicinity of the stone to develop strategies for adapting treatment parameters. Aims 2 and 3 of this proposal focus on understanding and exploiting mechanisms of stone fracture to develop advanced BWL treatment strategies. Aim 2 involves experimental testing of strategies for spatially and temporally manipulating BWL exposures to improve fragmentation. Aim 3 employs numerical simulation tools to identify fracture mechanics in different stone geometries and inform strategies for inducing and detecting fracture in other Aims. The proposed studies are designed synergistically with clinical trials in Projects 1 and 3, studies on stone imaging and manipulation in Project 1, and studies on BWL-related injury in Project 3. The work will benefit public health by improving the success of BWL as a noninvasive alternative for stone patients.