Improvement of lithotripters by ultrasound imaging and backscatter tecniques

描述（由申请人提供）：本申请涉及广泛的挑战领域（06），使能技术，主题06-DK-104使能技术用于预防和治疗NIDDK使命中的疾病。例如，优先领域包括：改进医疗设备，如...碎石机，以尽量减少手术并发症。冲击波碎石术（SWL）是最常见的治疗肾结石的大小范围从约2 - 20毫米：肾结石折磨13%的男性和7%的女性在美国，这些数字正在上升。肾结石的患病率取决于种族，性别，年龄和地理位置;然而，结石形成者可以是任何年龄，许多人一次发展多个结石。有些结石自然排出;然而，在美国，那些没有通过的患者每年接受超过200万次门诊治疗，占所有住院治疗的1%。在大多数碎石机中，体外产生的冲击波集中在固定位置。患者通常在麻醉或清醒镇静状态下，将结石定位在该焦点区域内。在约2 Hz（范围1-4 Hz）下施加1500和4000之间的冲击波。冲击波通过水进入人体。目前所有的碎石机都将SW源封装在与患者皮肤耦合的充水枕头中。治疗结果通过1至3个月后的结石清除率和再治疗率来衡量。不同机器的结石去除率从40-90%不等;较新的机器具有较低的结石去除率和较高的再处理率。虽然碎石术仍然占结石病治疗的一半以上，但它正逐渐被微创手术所取代，如输尿管镜和经皮肾镜取石术。这些更具侵入性的手术可能是具有更高冲击波（SW）振幅和更小病灶体积的较新商业版本的碎石机的结果。这些更高的振幅和更小的病灶通常导致更低效率的结石粉碎和更多的组织损伤。碎石术引起急性组织损伤，可能导致慢性不良反应。肾组织的急性损伤主要是出血性病变，取决于SW剂量。在猪动物模型中的研究显示，1000次SW后出血占功能性肾体积的0.3%，2000次SW标准临床剂量后出血占功能性肾体积的6.1%，8000次SW后出血占功能性肾体积的13.8%。反应高度依赖于剂量，但是非线性的，最大的损伤发生在1000和2000 SW之间。我们的研究表明，碎石机有效性降低的大部分原因是靶向不良和治疗进展的反馈有限。特别是，由于病灶体积更集中，呼吸调节有限，超过一半的SW输送完全错过结石并不罕见，并且这些更强烈的SW增加了组织损伤。此外，由于常规碎石机确定结石何时被充分破碎的能力有限，因此通常标准的做法是递送全剂量的SW，即使结石可以在低得多的剂量下被完全破碎。在这个应用中，我们建议通过开发工程概念和方法来改进碎石机，这些概念和方法能够更精确地检测和定位结石，以及实时定位和结石粉碎监测方法。通过改进靶向，并向泌尿科医生提供实时反馈，碎石机可能会大大改善患者的预后。在这项工作中开发的特定设备和方法将在猪动物模型以及正在进行的人类治疗中进行测试。成功完成本提案中概述的任务将有可能快速纳入商业碎石机。 公共卫生相关性：冲击波碎石术（SWL）是最常见的治疗肾结石的大小范围从约2 - 20毫米：肾结石折磨13%的男性和7%的女性在美国，这些数字正在上升。虽然碎石术仍然占结石病所有治疗的一半以上，但它正逐渐被微创手术所取代，如输尿管镜检查和经皮肾镜取石术，主要是因为新一代碎石机在碎石方面效果较差，并引起额外的组织损伤。本提案的目的是在碎石治疗期间向泌尿科医生提供即时反馈，以改善结石破碎并减少肾脏损伤。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06), Enabling Technologies, Topic 06-DK-104 Enabling technology for the prevention and treatment of diseases within the NIDDK mission. Priority areas include, for example: Improvement of medical devices such as...lithotriptors to minimize complications of procedures. Shock Wave Lithotripsy (SWL) is the most common treatment for kidney stones in the size range from about 2 - 20 mm: Kidney stones afflict 13% of men and 7% of women in the U.S. and these numbers are rising. The prevalence of kidney stones varies dependent on race, sex, age, and geographic location; however, stone formers can be any age, and many develop multiple stones at a time. Some stones pass spontaneously; however, those that don't pass account for over 2 million outpatient treatments and 1% of all hospitalizations annually in the U.S. In most lithotripters, shock waves generated outside the body are focused to a fixed location. The patient, usually under anesthesia or conscious sedation, is positioned with the stone within this focal zone. Between 1500 and 4000 shock waves are applied at about 2 Hz (range 1-4 Hz). The shock waves travel through water into the body. All current lithotripters have the SW source enclosed in a water-filled pillow that is coupled to the patient's skin. Treatment outcome is measured by stone-free rates after 1 to 3 months, and by re-treatment rates. Stone-free rates range from 40-90% with different machines; newer machines have lower stone-free rates and higher re-treatment rates. Although lithotripsy still accounts for more than half of all treatments for stone disease, it is gradually being replaced by minimally-invasive procedures, such as ureteroscopy and percutaneous nephrolithotomy. These more invasive procedures are likely the result of newer commercial versions of lithotripters having higher shock wave (SW) amplitudes and smaller focal volumes. These higher amplitudes and smaller foci often result in less efficient stone comminution and more tissue damage. Lithotripsy causes acute tissue injury that can lead to chronic adverse effects. The acute injury to kidney tissue is primarily a hemorrhagic lesion that is dependent on the SW dose. Studies in a porcine animal model show hemorrhage occupies 0.3% of the functional renal volume following 1000 SWs, 6.1% following a standard clinical dose of 2000 SWs, and 13.8% after 8000 SWs. The response is highly dependent on dose but is nonlinear, with the greatest injury occurring between 1000 and 2000 SWs. Our research has demonstrated that much of this reduced effectiveness of lithotripters is due to poor targeting and to limited feedback on the progress of the treatment. In particular, with more concentrated focal volumes, and limited accommodation for respiration, it is not uncommon for more than half of the SWs delivered to completely miss the stone-and with these more intense SWs-increased tissue damage. Additionally, because there is limited ability of conventional lithotripters to determine when the stone is sufficiently fragmented, it is often standard practice to deliver a full dose of SWs, even though the stone may be fully fragmented at much lower doses. In this application, we propose to improve lithotripters by developing engineering concepts and methodologies that enable more precise detection and localization of the stone, as well as real-time targeting and stone comminution-monitoring approaches. By improving targeting, and providing real-time feedback to the urologist, it is likely that lithotripters can realize greatly improved patient outcomes. The specific devices and methodologies to be developed in this effort will be tested on a porcine animal model as well as in ongoing human treatments. Successful accomplishment of the tasks outlined in this proposal will have potential for rapid incorporation into commercial lithotripters. PUBLIC HEALTH RELEVANCE: Shock Wave Lithotripsy (SWL) is the most common treatment for kidney stones in the size range from about 2 - 20 mm: Kidney stones afflict 13% of men and 7% of women in the U.S. and these numbers are rising. Although lithotripsy still accounts for more than half of all treatments for stone disease, it is gradually being replaced by minimally- invasive procedures, such as ureteroscopy and percutaneous nephrolithotomy, mostly because new generation lithotripters are less effective at stone fragmentation and induce additional tissue damage. The goal of this proposal is to provide immediate feedback to the urologist during lithotripsy treatment that will improve stone break-up and reduce kidney damage.