Interactive Effects of Combined Imaging, BWL, and Ultrasonic Propulsion

项目摘要/摘要--项目1 项目1将调查潜在的机制并测试集成特定于石材的好处(S- 模式)超声(US)成像、突发波碎石(BWL)、超声推进(UP)和声学 拖拉机光束成像，粉碎，排出尿路结石。尿路结石是最昂贵的非 恶性泌尿系疾病。在办公室或办公室内非侵入性地打碎石块和排出碎片的能力 诊所设置具有降低风险、降低成本和改善护理的潜力。本项目旨在回答 这一革命性愿景的主要科学障碍是：找到石头，打破石头，驱逐石头。 在目标1中，项目1和项目3将进行BWL的第一次人体测试。我们将通过输尿管镜观察 人体结石在体内的碎裂。与BWL的第一次测试相比，我们将比较粉碎 在根据反馈调整输出的情况下，采用BWL的有效性和安全性。至少， 在以反馈为基础的适应性对照组中，UP将与BWL交叉，后者处于初步的临床前 研究将结石粉碎速度提高了三倍，并通过以下方式实现了治疗终点的视觉反馈 分散成串的碎片，否则看起来就像一块完好无损的石头。 在目标2中，我们将对碎片化和驱逐的好处和风险进行随机对照试验 泌尿外科诊所里的结石。我们会将不干预比作联合应用BWL和UP进行驱逐 来移走石头。结石将被S模式成像打靶，被BWL粉碎，并被UP驱逐以方便 从尿路自然排出。结石负担、不良事件和生活质量(QOL) 分别通过成像、电话和图表回顾以及威斯康星斯通生活质量问卷进行测量。 重要的是要定位和瞄准在标准成像中不总是看到的小石头。我们观察到 即使是低幅度UP或BWL脉冲也具有与多普勒超声结石检测的协同效应 增加了石头与背景图像的对比度。在目标3中，我们将添加低频脉冲 从与S模脉冲相一致的向上探测和测量信杂比的改善 这些图像。三维(3D)S模式成像将通过在 治疗探头。将进行一项盲法研究，以定位植入猪体内的小结石(n=20)以测量 具有和不具有低频增强的灵敏度、特异度和用户变异性。 最后，在目标4中，我们讨论了如何从狭小的空间中排出碎片。我们将在体内开发和验证一种 远程牵引束可抓取和携带碎片穿过复杂的3D尿路和排出尿路 肾脏。我们将a)使用3D US成像来可视化路径，b)创建光束来移动石头，以及c)陷阱 并尝试从猪的肾脏中排出结石(n=20)。我们将比较计算和测量结果 一系列声强、波束和石头大小、数量、形状和成分的作用力。

PROJECT SUMMARY/ABSTRACT - Project 1 Project 1 will investigate the underlying mechanisms and test the benefits of integrating stone-specific (S- mode) ultrasound (US) imaging, burst wave lithotripsy (BWL), and ultrasonic propulsion (UP) and of acoustic tractor beams to image, comminute, and expel urinary stones. Urinary stone disease is the costliest non- malignant urologic disease. The ability to non-invasively break stones and expel the fragments in an office or clinic setting has the potential to reduce risk, reduce cost, and improve care. This Project seeks to answer the major scientific hurdles to this revolutionary vision: find the stone, break the stone, and expel the stone. In Aim 1, Project 1 with Project 3 will conduct the first-in-human test of BWL. We will observe by ureteroscopy the fragmentation of humans stones in vivo. To the first test of BWL alone, we will compare the comminution effectiveness and safety of BWL employed where the output is adapted in response to feedback. At a minimum, in the feedback-based, adaptive control group, UP will be interleaved with BWL, which in preliminary preclinical studies accelerated stone comminution threefold, and also enabled visual feedback on treatment endpoint by dispersing clusters of fragments that otherwise appeared as an intact stone. In Aim 2, we will conduct a randomized controlled trial of the benefits and risks of fragmenting and expelling stones in a urology clinic. We will compare no intervention to expulsion by combined application of BWL and UP to remove stones. Stones will be targeted by S-mode imaging, broken by BWL, and expelled by UP to facilitate natural clearance from the urinary tract. Stone burden, adverse events, and Quality of Life (QOL) will be measured by imaging, telephone and chart reviews, and the Wisconsin Stone QOL questionnaire, respectively. It is important to locate and target small stones not always seen on standard imaging. We have observed that even low amplitude UP or BWL pulses have a synergistic effect with Doppler US stone detection resulting in increased contrast of the stone against the background image. In Aim 3, we will add low frequency pulses from the UP probe in concert with the S-mode pulses and measure the improvement of signal to clutter ratio in the images. Three-dimensional (3D) S-mode imaging will be generated by rotating the imaging probe within the therapy probe. A blinded study to localize small stones implanted in a pig (n=20) will be conducted to measure sensitivity, specificity, and user variability with and without the low frequency enhancement. Lastly in Aim 4 we address how to expel fragments from tight spaces. We will develop and validate in vivo a remote tractor beam to grasp and carry fragments through the complex 3D path of the urinary space and out of the kidney. We will a) visualize with 3D US imaging the path, b) create beams to move the stone, and c) trap and attempt to expel stones from the kidneys of pigs (n=20). We will compare calculations and measurements of the forces for a range of acoustic intensities, beams, and stone sizes, numbers, shapes, and compositions.