Burst Wave Lithotripsy for the Treatment of Ureteral Calculi

突发波碎石术治疗输尿管结石

• 批准号: 9361764
• 负责人: Oren Levy
• 金额: $ 77.01万
• 依托单位: SONOMOTION, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9361764
• 关键词: Accident and Emergency department; Acoustics; Address; Algorithms; American; Amplifiers; Anesthesia procedures; Animal Model; Animals; Bathing; Blood; Clinic; Clinical Trials; Collection; Complication; Conscious Sedation; Cost of Illness; Data; Devices; Diabetes Mellitus; Disease; Distal; Documentation; Dose; Effectiveness; Electronics; Elements; Emergency department visit; Evaluation; Extracorporeal Shockwave Lithotripsy; Family suidae; Fracture; Frequencies; Goals; Healthcare; Healthcare Systems; Histologic; Human; Image; Implant; In Vitro; Injury; Intervention; Intestines; Kidney; Kidney Calculi; Lead; Lithotripsy; Location; Methods; Modeling; Monitor; Morphologic artifacts; Obesity; Operative Surgical Procedures; Organ; Output; Patient observation; Patients; Phase; Physicians; Physiologic pulse; Procedures; Productivity; Pulse Pressure; Research; Risk; Risk Factors; Safety; Sedation procedure; Shock; Source; Stress; Structure; Symptoms; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Transducers; Ultrasonography; Ureter; Ureterolithiasis; Ureteroscopy; Urinary Calculi; Urine; Visit; Water; Work; base; cost; design; effective therapy; flexibility; imaging system; improved; in vivo; minimally invasive; novel; pressure; prototype; public health relevance; rib bone structure; safety study; virtual

 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).

 描述（由申请人提供）：重要性：尿路结石造成了重大的医疗负担，美国每年的费用超过100亿美元。随着糖尿病和肥胖等风险因素变得更加普遍，预计结石病对医疗保健系统的影响将继续增长。尤其是输尿管结石，因为它们通常是有症状的，并且自发通过是结石大小和位置的重要功能，因此构成了管理挑战。观察等待结合驱逐治疗是一线方法，但可能导致重复的医生和/或急诊科就诊，丧失生产力，并对患者造成压力。对于主动干预，体外冲击波碎石术（SWL）通常需要重复或二次手术以达到无结石状态。输尿管镜是一种微创手术，其结石清除率高于SWL，但并发症发生率较高。工艺流程：爆破波碎石术（BWL）是一种新型的、无创的碎石方法，有可能显著改善输尿管结石的治疗。BWL使用多周期、低振幅的超声脉冲而不是冲击波来非侵入性地诱导结石破裂。这种方法有可能降低损伤、手术并发症和额外手术的风险，并显著减少手术时间和成本。此外，所使用的低脉压幅度可以排除麻醉的需要，从而提供了观察等待的有吸引力的替代方案。初步数据：体外研究表明，该技术能够打破人类中发现的所有常见类型的结石。结果还表明，可以通过改变超声频率来控制碎片大小，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，在猪动物研究中，碎石所需的压力水平显著低于诱导肾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如何改变BWL参数的技术问题，以治疗输尿管内阻塞的结石，与水浴中无结石相比。这将需要组装BWL换能器和放大器（第I阶段目标1），并进行体外研究，以确定在输尿管体模内破碎结石所需的压力水平和剂量（时间）（第I阶段目标2）。第二阶段确定了在瞄准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），并设计了专用于这些窗口的商业原型换能器，并操作了第一阶段确定的声学参数（第二阶段目标2）。BWL系统将由具有专门算法的超声成像系统引导，以增强靶向并检测空化，从而监测和控制损伤（第II阶段目标3）。将在猪动物模型中测试所开发系统的安全性和有效性（II期目标4、5）。