In-Office, Ultrasound-Based Breakage and Removal of Urinary stones

总体汇总 该计划项目赠款的主要重点是发现基础和翻译 创建基于办公室的手持式超声设备所需的知识，以定位、分离、破坏和 将结石和结石碎片从泌尿空间排出，以促进自然清除。该系统将 避免昂贵和低效的急诊室访问，通常包括重复暴露于 电离辐射从诊断成像，并将显着减少往往冗长（数天至数周） 患者在排石和进行排石手术之前必须忍受等待时间。 由于所提出的治疗系统是完全无创的，患者将在门诊接受治疗。 此外，由于该系统被设计成有效且无痛地破碎任何尺寸的结石并排出结石， 从肾脏碎片，治疗有症状和无症状的结石，使用这种 技术将降低与当前治疗相关的高再治疗率和结石事件复发率， 手术取石。 在这项工作中，我们将结合联合收割机碎石爆破波碎石术（BWL），清除碎片 通过超声推进（UP）和结石特异性超声成像（S模式）集成到一个集成系统中 其中在治疗期间响应于实时声反馈调整暴露策略， 提高粉碎效率和患者安全。我们将通过数字调查来调整治疗方法 在实验室试验中，研究了破碎的主要机理--空化和弹性波 在一个广泛的参数空间。我们将开发基于声学的反馈，包括模型- 基于机器学习和被动声映射（PAM）的气泡场信号， 调整能量输出。我们将研究肾脏的形态和功能反应， 活体动物和离体灌注猪肾，并寻求组织保护性治疗策略 例如功率斜坡。 这些研究将包括第一次人体BWL测试，其中我们将比较粉碎 有和无自适应输出控制治疗对声刺激响应的有效性和安全性 反馈此外，我们还将进行一项随机对照试验，以了解碎片化的益处和风险。 并在临床上排出有症状和无症状的结石。该系统的应用 在人类中使用，我们将完善和验证UP和S模式的使用，以改善结石和 碎片检测我们着眼于结石管理的未来，将在体内开发和验证 一个体外声波牵引光束来抓住和携带碎片通过复杂的三个- 在泌尿空间的三维路径和肾脏外。

OVERALL SUMMARY The main focus of this Program Project Grant is to discover the foundational and translational knowledge needed to create an office-based handheld ultrasound device to target, detach, break, and expel stones and stone fragments from the urinary space to facilitate natural clearance. This system will obviate costly and inefficient emergency department visits that typically include repetitive exposure to ionizing radiation from diagnostic imaging, and will significantly reduce the often lengthy (days to weeks) wait time patients must endure before procedures for stone removal can be scheduled and performed. As the proposed therapy system is entirely noninvasive, patients will be treated on an outpatient basis. Further, as the system is designed to efficiently and painlessly break stones of any size and expel the fragments from the kidney, the treatment of both symptomatic and asymptomatic stones using this technology will reduce the high retreatment and stone event recurrence rates associated with current surgical interventions for stone removal. In this effort, we will combine stone breakage by burst wave lithotripsy (BWL), clearance of fragments by ultrasonic propulsion (UP), and stone-specific ultrasound imaging (S-mode) into an integrated system in which exposure strategies are adapted during treatment in response to real-time acoustic feedback to enhance comminution efficiency and patient safety. We will tailor treatment by investigating numerically and in lab tests the primary mechanisms - cavitation and elastic waves - involved in the comminution process over a broad parameter space. We will develop acoustics-based feedback including model- based, machine learning and passive acoustic mapping (PAM) of the bubble field to signal the need to adjust the energy output. We will investigate the morphological and functional response of the kidney in living animals and in ex vivo perfused porcine kidneys, and pursue tissue protective treatment strategies such as power ramping. These studies will include the first in-human test of BWL in which we will compare the comminution effectiveness and safety of treatment with and without adaptive output control in response to acoustic feedback. In addition, we will conduct a randomized controlled trial of the benefits and risks of fragmenting and expelling symptomatic and asymptomatic stones in the clinic. Toward application of the system for use in humans, we will refine and validate the use of UP and S-mode together to improve stone and fragment detection. With our eye on the future of stone management, we will develop and validate in vivo an extracorporeal acoustic tractor beam to grasp and carry fragments through the complex three- dimensional path of the urinary space and out of the kidney.