Noninvasive, non-ionizing localization and clearance of kidney stones

描述（由申请人提供）：10%的美国人会患上肾结石。每年有300万美国人寻求治疗，总治疗费用超过20亿美元。根据治疗方式的不同，最初的成功率从70%到90%以上不等，但有一半的患者在5年内会复发。结石的后续手术治疗是复杂和个性化的，但会耗费大量资源，造成额外的不适，并可能使患者多次暴露于x光下。肾盂内的小结石碎片很可能自然排出，但位于肾盂下部的结石碎片更有可能留下并成为问题。我们开发了一种手持式脉冲超声设备，可以无创地从肾脏中排出结石碎片（或小结石）。我们还开发了一种独特的超声成像方法，可以显着增强肾结石的可视化，这为平面x射线和计算机断层扫描（CT）的电离辐射提供了一种安全的选择。一个原型装置已经由市售的诊断超声成像仪和探头设计而成。动物模型的初步结果表明，我们可以在不到5分钟的时间内将结石从下肾盏定位并安全地重新定位到肾盂输尿管接点（UPJ），这一过程可以在办公室就诊期间轻松完成。本提案使用人体受试者的目的是评估该装置重新定位石头碎片的能力。我们将首先测量增强超声定位与CT的成像精度作为金标准。与监管顾问合作，我们将准备向美国食品和药物管理局（FDA）申请研究器械豁免（IDE），以测试在人类受试者中重新定位结石的治疗策略。长期目标是为泌尿科医生提供一种新的非侵入性手术选择，以清除肾脏中的结石碎片和小结石。该装置可用于清除冲击波碎石（或输尿管镜检查等侵入性结石清除）后残留的碎片，并可在小结石出现症状之前预防性地将其排出肾脏。这种结石重新定位装置及其补充的结石成像方法有可能提供更安全、更有效的治疗，并显著降低医疗成本。

DESCRIPTION (provided by applicant): Ten percent of the U.S. population will develop kidney stones. Three million Americans seek treatment each year, and total treatment cost is over $2B. Initial success rates range from ~70% to greater than 90% depending on the type of treatment performed, but stones will recur in half the patients within 5 years. Follow- up surgical management of stones is complex and individualized but expends significant resources, creates additional discomfort and can expose the patient to X-rays many times. Small stone fragments in the renal pelvis have a good chance of passing naturally, but fragments located in the lower calyces are more likely to remain and become problematic. We have developed a handheld pulsed-ultrasound device to non-invasively expel stone fragments (or small stones) from the kidney. We have also developed a unique ultrasound imaging method to dramatically enhance the visualization of kidney stones, which provides a safe alternative to the ionizing radiation of plane X-ray and computerized tomography (CT). A prototype device has been engineered from a commercially available diagnostic ultrasound imager and probe. Preliminary results in animal models show we can localize and safely repositioning stones from the lower calyx to the ureteropelvic juncture (UPJ) in less than 5 minutes, a procedure that could easily be completed during an office visit. The objective of this proposal using human subjects is to assess the ability of this device to reposition stone fragments. We will first measure, imaging accuracy of enhanced ultrasound localization compared to CT as the gold standard. In partnership with a regulatory consultant, we will prepare an application to the U.S. Food and Drug Administration (FDA) for an Investigational Device Exemption (IDE) to test the therapeutic strategy of repositioning stones in human subjects. The long-term goal is to provide urologists with a new non-invasive surgical option to clear stone fragments and small stones from the kidney. This device would be used to clear residual fragments remaining after shock wave lithotripsy (or invasive stone removal such as ureteroscopy), and could be a means to prophylactically expel small stones from the kidney before they become symptomatic. This stone repositioning device and its complementary stone imaging methodology have the potential to deliver safer, more effective treatments and significantly lower healthcare costs. PUBLIC HEALTH RELEVANCE: The proposal is to transition technology to detect and reposition kidney stones with ultrasound to facilitate stone clearance. As such kidney stone patients who account for 10% of the US population might be spared ionizing radiation of stone detection by x-ray computerized tomography and spared surgery or lithotripsy for initial or follow-on treatment.