Noninvasive fragmentation of urinary calculi with focused ultrasound bursts

 描述（由申请人提供）：拟议职业发展奖的候选人是亚当麦克斯韦博士，他是一名生物医学工程师，在医学超声研究，特别是冲击波碎石术和高强度聚焦超声治疗方面有10多年的经验。他研究了声波与组织的物理相互作用，开发了研究和临床原型系统，并研究了超声治疗的新应用。申请这个职业发展奖的目的是为了麦克斯韦博士培养必要的素质和能力，成为一个成功的独立研究人员，并在三位经验丰富的导师的指导下获得尿石症的专业知识，迈克尔贝利博士，乔纳森哈珀，和亨特韦塞尔。华盛顿大学是一所领先的研究机构，麦克斯韦博士计划在这里从事研究和职业发展。他将得到应用物理实验室工业和医疗超声中心泌尿科和医疗超声部门内具有结石管理专业知识的协作团队的支持。他提出的研究将研究一种潜在的治疗尿石症的新方法。尿石症是一种常见疾病，在其一生中影响约1/11的个体，并对美国医疗资源造成巨大负担。在过去的30年里，泌尿系结石的治疗已经引入了几种新的方法，包括冲击波碎石术（SWL），输尿管镜和经皮肾镜取石术。SWL是唯一的非侵入性结石手术，但在一次治疗中使患者无结石的可能性大大低于其他方法，并且在新的碎石机中有所下降。开发更有效的碎石机仍然是一个尚未满足的临床挑战。虽然在这项技术的临床引入过程中，冲击和结石之间的物理相互作用还没有得到很好的理解，但最近的研究已经建立了SWL中结石破裂的机制。基于这项工作，提出了一种新型的碎石术，使用广泛聚焦的超声波脉冲，而不是冲击波。初步数据显示，冲击波碎石术（BWL）能够在短短10秒内分解结石。此外，在手术过程中产生的碎片的大小可以通过超声频率来控制，从而增强了产生容易被患者通过的小碎片的治疗。本提案的目的是建立一个科学的理论基础，指导爆裂波碎石术的发展。特别是，该项目提出研究超声脉冲与结石和组织的物理相互作用，并使用此信息来确定治疗参数。该提案的具体目标是：1）开发并表征用于BWL研究的合适超声源，2）确定BWL导致结石破裂的机械相互作用，以及3）识别BWL导致组织损伤的机械效应。麦克斯韦博士的长期研究目标是将这项技术转化为临床上有用的治疗方法，提高结石管理的护理标准。

 DESCRIPTION (provided by applicant): The candidate of the proposed Career Development Award is Dr. Adam Maxwell, a biomedical engineer with over 10 years of experience in medical ultrasound research, particularly shock wave lithotripsy and high- intensity focused ultrasound therapy. He has investigated physical interactions of acoustic waves with tissues, developed research and clinical prototype systems, and researched new applications for ultrasound therapies. The purpose of applying for this Career Development Award is for Dr. Maxwell to cultivate the qualities and abilities necessary to be a successful independent researcher and obtain expertise in urolithiasis under the guidance of three experienced mentors, Drs. Michael Bailey, Jonathan Harper, and Hunter Wessells. The University of Washington is a leading research institution at which Dr. Maxwell plans to pursue his research and career development. He will be supported by a collaborative team with expertise in stone management within the Department of Urology and medical ultrasound in the Center for Industrial and Medical Ultrasound at the Applied Physics Laboratory. His proposed research will investigate a potential new treatment for urolithiasis. Urolithiasis is a common disease that affects approximately 1 in 11 individuals during their lifetime and presents a large burden on U.S. healthcare resources. In the last 30 years, management of urinary tract stones has seen the introduction of several novel approaches, including shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy. SWL is the only noninvasive procedure for stones, but the likelihood of rendering patients stone-free in a single session is considerably lower than other methods, and has declined in newer lithotripters. Development of a more effective lithotripter remains an unmet clinical challenge. While the physical interactions between shocks and stones were not well understood during this technology's clinical introduction, recent research has established the mechanisms of stone fracture in SWL. Based on this work, a novel type of lithotripsy using widely focused bursts of ultrasound rather than shock waves is proposed. Preliminary data shows that burst wave lithotripsy (BWL) is capable of disintegrating stones in as little as 10 seconds. Furthermore, the size of fragments generated during the procedure can be controlled by the ultrasound frequency, potentiating a therapy that produces small fragments easily passed by patients. The goal of this proposal is to create a scientific rationale that will guide the development of burst wave lithotripsy. In particular, this project proposes to investigate the physical interactions of ultrasound bursts with stones and tissue, and use this information to determine therapy parameters. The specific aims of the proposal are: 1) Develop and characterize a suitable ultrasound source for BWL research, 2) Determine the mechanistic interactions leading to stone fracture by BWL, and 3) Identify the mechanical effects of BWL leading to tissue damage. Dr. Maxwell's long-term research goal is to translate this technology into a clinically useful treatment that improves the standard of care for stone management.