Innovative Strategies for Improved outcomes in Nephrolithiasis

描述(由申请人提供)：改善肾结石预后的创新策略。该计划项目赠款的主要重点是开发和改进基于超声波的技术和治疗方案，以改进非侵入性去除肾脏结石的方法，以改善患者的预后。在这项工作中，我们将改进使用超声波推进(UP)的新技术，将结石和残留的结石碎片从肾盆肾系统推到输尿管-盆腔交界处，然后沿着输尿管下行。UP系统建立在商用的超声(US)平台上，我们已对该平台进行了配置，以提供一套独特的针对石块的成像模式(S模式)，该模式专为检测石块(即使是非常小的、1毫米的石块碎片)而量身定做，确定碎石碎片的大小，检测干扰石块破碎的声屏障的空化情况，并对组织中的空洞进行定位，从而发出组织损伤的信号。我们将使用UP和S模式成像来提高冲击波碎石术的效率，方法是分散产生屏蔽的碎石碎片，并能够精确确定结石破碎终点，从而使患者不会受到不必要的过度治疗。我们还将继续开发、改进和验证一种新的非侵入性方法，该方法使用聚焦的低频脉冲US(猝发波碎石，BWL)来将结石减少到临床上微不足道的小颗粒，并对周围组织造成最小的伤害。SWL的过度治疗与增加不良反应有关，也是FDA限制SWL剂量的基础，SWL剂量限制通常会阻止患者使用足以使患者结石排出的剂量进行治疗。我们将在我们发现的保护肾脏免受伤害的SWL治疗策略的基础上，设计出大大超过FDA目前的SWL剂量限制，但完全安全的治疗方案。也就是说，我们将证明SWL可以在不造成额外伤害的情况下超过单次治疗限制，从而允许使用足够的SWS治疗来完全粉碎较大的结石负担或清除否则难以粉碎的结石。与我们改善结石患者治疗结果的目标一致，我们将进行一项多中心前瞻性临床试验，以确定通过输尿管肾镜(在UP的辅助下)取出“亚临床”附着结石是否可以防止结石复发，从而改善长期结果。

DESCRIPTION (provided by applicant): Innovative Strategies for Improved Outcomes in Nephrolithiasis. The main focus of this Program Project Grant is to develop and refine ultrasound-based technologies and treatment protocols to improve the noninvasive removal of stones from the kidney with the goal of improving patient outcomes. In this effort, we will refine new technology that uses ultrasonic propulsion (UP) to push stones and residual stone fragments out of the renal pelvicalyceal system and on to the uretero-pelvic junction for passage down the ureter. The UP system is built upon a commercially available ultrasound (US) platform that we have configured to deliver a suite of unique stone-specific imaging modalities (S-mode) specifically tailored to detect stones (even very small, <1 mm, stone fragments), determine fragment size, detect cavitation indicative of the acoustic shielding that interferes with stone breakage, and localize the cavitation in tissue that signals the on- set of tissue injury. We will use UP and S-mode imaging to improve the efficiency of shock wave lithotripsy (SWL) by dispersing fragments that create shielding and by enabling precise determination of the stone breakage endpoint so that patients are not needlessly over-treated. We will also pursue the development, refinement, and validation of a novel noninvasive method that uses focused, low-frequency pulsed US (burst wave lithotripsy, BWL) to reduce stones to small, clinically insignificant particles with minimal injury to surrounding tissue. Over-treatment by SWL is linked to increased adverse effects and is the basis for FDA limits on SW-dose, limits that often prevent treatment with a dose sufficient to render the patient stone free. We will build upon our discovery of SWL treatment strategies that protect the kidney from injury to devise treatment protocols that dramatically exceed current FDA limits for SW dose, yet are entirely safe. That is, we will demonstrate that single session treatment limits for SWL can be exceeded without causing added injury, thus allowing treatment with enough SWs to fully comminute a large stone burden or eliminate stones otherwise difficult to break. Consistent with our goal of improving treatment outcomes for stone patients, we will conduct a multicenter prospective clinical trial to determine if the removal of 'subclinical' attached stones by ureterorenoscopy (assisted by UP) will forestall stone recurrence, thereby improving long-term outcomes.