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 NIDDK任务中预防和治疗疾病的使能技术。优先领域包括，例如：医疗设备的改进，例如…碎石机，以尽量减少程序的并发症。冲击波碎石术（SWL）是肾结石最常用的治疗方法，肾结石的大小在2 - 20毫米之间。在美国，13%的男性和7%的女性患有肾结石，而且这个数字还在上升。肾结石的患病率因种族、性别、年龄和地理位置而异；然而，结石形成者可以发生在任何年龄，而且许多人一次会形成多个结石。有些结石是自发排出的；然而，在美国，每年有超过200万的门诊治疗和1%的住院治疗都没有通过。在大多数碎石机中，体外产生的冲击波集中在一个固定的位置。患者通常在麻醉或清醒镇静状态下，将结石放置在病灶区域内。在1500到4000之间的冲击波以大约2赫兹（范围1-4赫兹）施加。冲击波通过水进入人体。目前所有的碎石机都将SW源封装在一个充满水的枕头中，该枕头与患者的皮肤相连。治疗结果以1 - 3个月后无结石率和再治疗率来衡量。不同机器的无石率在40-90%之间；较新的机器有较低的脱石率和较高的再处理率。尽管碎石术仍占所有结石疾病治疗的一半以上，但它正逐渐被输尿管镜检查和经皮肾镜取石等微创手术所取代。这些更具侵入性的手术可能是由于新的商用碎石机具有更高的冲击波（SW）振幅和更小的震源体积。这些较高的振幅和较小的病灶往往导致较低效率的结石粉碎和更多的组织损伤。碎石术会造成急性组织损伤，从而导致慢性不良反应。肾组织的急性损伤主要是一种依赖于SW剂量的出血性损伤。在猪动物模型中进行的研究表明，1000 SWs后出血占功能肾体积的0.3%，标准临床剂量2000 SWs后为6.1%，8000 SWs后为13.8%。反应高度依赖于剂量，但呈非线性，最大的损伤发生在1000至2000 SWs之间。我们的研究表明，碎石机的有效性降低很大程度上是由于靶向性差和对治疗进展的反馈有限。特别是，在更集中的病灶体积和呼吸调节有限的情况下，超过一半的SWs完全错过结石的情况并不罕见，而且这些更强烈的SWs会增加组织损伤。此外，由于常规碎石机判断石料何时已充分破碎的能力有限，因此通常的标准做法是使用全剂量的SWs，即使石料可能以低得多的剂量完全破碎。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，使其能够更精确地检测和定位石头，以及实时瞄准和石头粉碎监测方法。通过提高靶向性，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具体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迅速纳入商用碎石机。

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.