Development of a Next-Generation Shock Wave Lithotripter

描述（由申请人提供）：自20世纪80年代初Domier Medical System引入冲击波碎石术（shock wave lithotripsy， SWL）以来，SWL技术在冲击波产生、聚焦、患者耦合和结石定位等方面都有了显著的发展。然而，尽管有了这些技术发展，SWL的基本工作原理仍然没有改变。在此期间，冲击波物理和生物效应的基础研究也得到了广泛开展，主要是在学术研究实验室进行的。特别是，过去五年的研究已经开始积累一些关于SWL工作机制和侧支组织损伤如何产生的关键见解。基于这些知识，我们开发了两种新的SWL技术，可以在多尼尔HM-3碎石机上轻松升级。为了证明原理，我们进行了一系列的体外和体内实验，证明了这些技术比目前的黄金标准——多米耶HM-3碎石机的优越性。因此，STTR提案的目标是将这些使能技术转化为下一代商用冲击波碎石机的开发，以改善石头粉碎，同时减少组织损伤。这项任务将通过杜克大学治疗学研究实验室和领先的冲击波碎石机分销商HealthTronics外科服务有限责任公司（HTRN）之间的协同合作来完成。该项目代表了SWL领域前所未有的学术和工业合作，拟议的产品将对尿石症的临床管理产生广泛的影响和显著的益处。在这个STTR提案的第一阶段，我们的具体目标是设计和建造一个基于原位脉冲叠加概念的原型冲击波发生器。将进行压力波形测量和体外模拟研究，以评估由原型冲击波发生器产生的石头破碎效率和血管破裂倾向。一旦具有与HM-3发电机相当性能的原型机建成，将在第二阶段进行全面的研究，包括在猪肾中植入人工结石的动物研究，以优化拟议的冲击波碎石机系统的设计。

DESCRIPTION (provided by applicant): Since the introduction of shock wave lithotripsy (SWL) in the earlier 1980s by Domier Medical System, the technology of SWL has evolved significantly in terms of the means for shock wave generation, focusing, patient coupling, and stone location. However, the fundamental working principle of SWL remains unchanged despite of these technical developments. During this period, extensive basic research in shock wave physics and bio effects has also been carried out, mostly in academic research laboratories. In particular, the research in the past five years has begun to accumulate some critical insights regarding the mechanisms by which SWL works and how collateral tissue injury may be produced. Based on this knowledge, we have developed two novel SWL technologies that can be easily upgraded on a Dornier HM-3 lithotripter. For proof of principle, we have performed a series of in vitro and in vivo experiments that demonstrate the superiority of these technologies to the current gold standard - the Domier HM-3 lithotripter. The objective of this STTR proposal, therefore, is to translate these enabling technologies to the development of a next-generation commercial shock wave lithotripter for improved stone comminution with simultaneously reduced tissue injury. This task will be carried out through a synergistic collaboration between the Therapeutics Research Laboratory at Duke University and the HealthTronics Surgical Services, LLC (HTRN), a leading distributor of shock wave lithotripters. This project represents an unprecedented academic and industrial collaboration in the field of SWL and the proposed product should generate widespread impact and significant benefit to the clinical management of urolithiasis. In Phase I of this STTR proposal, our specific aim is to design and construction of a prototype shock wave generator based on in situ pulse superposition concept. Pressure waveform measurements and in vitro phantom studies will be performed to assess the stone fragmentation efficiency and propensity for vessel rupture produced by the prototype shock wave generator. Once the prototype with performance comparable to a HM-3 generator is constructed, a comprehensive investigation including animal studies with implanted artificial stones in porcine kidney will be performed in phase II to optimize the design of the proposed shock wave lithotripter system.