Interactive Effects of Combined Imaging, BWL, and Ultrasonic Propulsion

项目摘要/摘要 - 项目 1 项目 1 将研究潜在机制并测试整合特定石材（S- 模式）超声（US）成像、爆裂波碎石术（BWL）、超声推进（UP）和声学 牵引光束成像、粉碎和排出尿路结石。泌尿系结石病是最昂贵的非 恶性泌尿系统疾病。能够在办公室或办公室内非侵入性地打碎石头并排出碎片 诊所环境有可能降低风险、降低成本并改善护理。该项目旨在回答 这一革命性愿景的主要科学障碍是：找到石头、打破石头、排出石头。 在目标 1 中，项目 1 和项目 3 将进行 BWL 的首次人体测试。我们会通过输尿管镜观察 人体结石在体内的碎裂。单独对BWL进行第一次测试，我们将比较粉碎 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， 在基于反馈的自适应对照组中，UP 将与 BWL 交替进行，这在初步临床前研究中 研究加速了结石粉碎速度的三倍，并且还通过以下方式实现了治疗终点的视觉反馈 分散的碎片簇原本看起来是完整的石头。 在目标 2 中，我们将进行一项随机对照试验，研究破碎和驱逐的好处和风险 泌尿外科诊所的结石。我们将结合应用 BWL 和 UP 来比较不干预和驱逐 去除石头。结石将通过S模式成像瞄准，通过BWL破碎，并通过UP排出以促进 从尿道自然清除。结石负担、不良事件和生活质量 (QOL) 将 分别通过成像、电话和图表审查以及威斯康星石生活质量问卷进行测量。 定位和瞄准标准成像中不常见的小结石非常重要。我们观察到 即使低幅度 UP 或 BWL 脉冲也与多普勒超声结石检测产生协同效应 增加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 来自 UP 探头与 S 模式脉冲的配合，并测量信号杂波比的改善 图像。三维 (3D) S 模式成像将通过在成像探头内旋转来生成 治疗探针。将进行一项盲法研究，定位植入猪（n = 20）体内的小石头，以测量 有或没有低频增强的灵敏度、特异性和用户可变性。 最后，在目标 4 中，我们解决了如何从狭小的空间中排出碎片。我们将开发并验证体内 远程牵引光束可抓取碎片并携带其穿过泌尿道复杂的 3D 路径并排出体外 肾脏。我们将 a) 通过 3D US 成像来可视化路径，b) 创建光束来移动石头，以及 c) 捕获 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 一系列声强、声束和石头尺寸、数量、形状和成分的力。

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.