BWL Interaction with Kidney Tissue

项目概要/摘要-项目3 爆破波碎石术（BWL）是一种新兴的基于超声的技术，显示出能够破坏 在医生办公室里治疗肾结石项目3将重点研究BWL的相互作用， BWL声音能量与实际的人的石头和组织。我们的项目在人类研究的广度上是独一无二的。 患者、动物模型、离体肾脏和体外模型，所有这些都得到数学建模的支持。在目标1中，我们 在人体中观察BWL碎石并监测BWL对肾组织的影响，测试 假设BWL将破碎人肾内的结石而不显著损伤肾组织。在这 目的是，项目3将与项目1合作，直接验证BWL在人体肾脏内的碎石效果， 同时研究BWL对组织的可见影响，添加和不添加自适应反馈控制 用于空化。将使用最先进的内窥镜检查对结石破裂和组织健康进行视觉记录 和石头分析技术。在目标2中，我们将从实验和理论上评估组织钙化的影响 关于其与BWL的相互作用，检验结石形成者常见的组织钙化水平将 不会增加BWL的伤害。这一目标将使用体外测试系统来实现，在该系统中， 材料将附着或嵌入组织模拟凝胶中，以模拟与肾脏相关的钙化。 乳头，并使用显微CT成像定量结果。所有这些实验都将与 由Freund实验室建模，使整体结果不仅仅是简单的经验，但设计，使更深层次的 将实现对BWL声能在结石形成者的组织中的作用机制的理解。在目标3中， 我们将通过测量肾脏形态和功能的变化来评估BWL的肾脏效应， 在活体猪模型中进行经皮BWL治疗，检验以下假设： BWL既安全又高效，可以使用预处理策略进行扩展， 肾脏组织猪模型将用于测量BWL在一定范围内对肾脏结构和功能的影响， 能量剂量高于和低于阈值，以诱导与损伤相关的超声可见空化。的安全 还将测试BWL和UP的交替应用。与软件一起工作的保护协议（例如，预处理 暂停）将测试对BWL的肾反应的影响。在目标4中，我们将评估BWL期间的组织健康， 声发射和离体灌注肾系统中组织损伤的生物力学模型，测试 假设来自气穴的声发射与生物力学组织模型相结合可用于监测 并提供实时反馈以避免或最小化附带组织损伤。被动声 标测（PAM）是一种允许在组织中实时检测和标测空化活动的技术。的 生物力学模型采用断裂力学来确定组织的粘弹性如何随着 BWL能量沉积在组织中。

PROJECT SUMMARY/ABSTRACT - Project 3 Burst wave lithotripsy (BWL) is an emerging ultrasound-based technology that shows promise of being able to destroy kidney stones in the setting of a physician’s office. Project 3 will be focusing its study of BWL on the interaction of the BWL sound energy with actual human stones and with tissue. Our project is unique in its breadth of study of human patients, animal models, ex vivo kidneys, and in vitro models, all supported by mathematical modeling. In Aim 1, we will conduct in human observations of breaking stones with BWL and monitor BWL effects on renal tissue, testing the hypothesis that BWL will break stones within the human kidney without significant damage to the kidney tissue. In this Aim, Project 3 will collaborate with Project 1 to directly verify the breaking of stones by BWL within human kidneys, and simultaneously study the visible effects of BWL on tissue, with and without the addition of adaptive feedback control for cavitation. Visual documentation of stone breakage and tissue health will be done using state-of-the-art endoscopy and stone analysis techniques. In Aim 2, we will assess experimentally and theoretically the effects of tissue calcification on its interactions with BWL, testing the hypothesis that levels of calcification in tissue common to stone formers will not result in increased damage by BWL. This aim will be accomplished using in vitro test systems in which human stone material will be attached to or embedded within tissue-mimicking gels to model calcifications associated with renal papillae, and the results quantitated using micro CT imaging. All of these experiments will be done hand-in-hand with modeling by the Freund lab so that the overall results are more than simply empirical, but designed so that a deeper understanding of the mechanisms of action of BWL sound energy in tissue of stone formers will be achieved. In Aim 3, we will evaluate renal effects of BWL by measuring changes in kidney morphology and function associated with transcutaneous BWL treatment in the living pig model, testing the hypothesis that the range of treatment parameters at which BWL is both safe and highly effective can be extended using pre-treatment strategies that afford protection to kidney tissue. The pig model will be used to measure effects of BWL on renal structure and function over a range of energy doses above and below the threshold to induce ultrasound-visible cavitation linked to injury. The safety of alternating application of BWL and UP will also be tested. Protection protocols that work with SW (e.g., pretreatment with pause) will be tested for effect on renal response to BWL. In Aim 4, we will assess tissue health during BWL from acoustic emissions and a biomechanical model of tissue damage in an ex vivo perfused kidney system, testing the hypothesis that acoustic emissions from cavitation, coupled to a biomechanical tissue model can be used to monitor the health of tissue during BWL and provide real-time feedback to avoid or minimize collateral tissue injury. Passive acoustic mapping (PAM) is a technique that allows for cavitation activity to be detected and mapped in tissue in real-time. The biomechanical model employs fracture mechanics to determine how the viscoelastic properties of tissue are altered as BWL energy is deposited in the tissue.