BWL Interaction with Kidney Tissue

项目摘要/摘要--项目3 爆震波碎石术(BWL)是一种新兴的基于超声波的技术，它显示出能够摧毁 医生办公室里的肾结石。项目3将把对BWL的研究集中在 BWL声能与真实的人体结石和组织。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、体外肾脏和体外模型，都得到了数学建模的支持。在目标1中，我们将 在人体内观察BWL碎石并监测BWL对肾组织的影响，测试 假设BWL将打破人类肾脏内的结石，而不会对肾脏组织造成重大损害。在这 AIM，项目3将与项目1合作，直接验证BWL在人体肾脏内粉碎结石的情况，以及 同时研究在加入和不加入自适应反馈控制的情况下，BWL对组织的可见效应 用于空化。将使用最先进的内窥镜检查进行结石破碎和组织健康的可视记录 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。 关于它与BWL的相互作用，测试了结石形成者常见组织中的钙化水平将 不会增加BWL造成的伤害。这一目标将使用体外测试系统来实现，在该系统中，人类结石 材料将附着在或嵌入到组织模拟凝胶中，以模拟与肾脏相关的钙化 乳头，并用显微CT成像对结果进行定量。所有这些实验都将与 由弗洛因德实验室进行建模，因此总体结果不仅是经验的，而且设计得更深入 我们将了解BWL声能在结石形成组织中的作用机制。在《目标3》中， 我们将通过测量与以下相关的肾脏形态和功能的变化来评估BWL的肾脏效应 在活猪模型中经皮BWL治疗，检验治疗参数范围为 哪种BWL既安全又高效，可以使用提供保护的前处理策略来推广 肾组织。猪模型将被用来测量BWL对肾脏结构和功能的影响 阈值以上和阈值以下的能量剂量会导致与损伤相关的超声波可见空化。的安全问题 还将测试BWL和UP的交替应用。与软件配合使用的保护协议(例如，预处理 将测试对BWL的肾脏反应的影响。在目标4中，我们将评估BWL期间的组织健康状况 声发射和体外灌流肾脏系统中组织损伤的生物力学模型，测试 假设空化产生的声发射与生物力学组织模型相结合可以用来监测 BWL期间的组织健康状况，并提供实时反馈，以避免或尽量减少侧支组织损伤。被动声学 标测(PAM)是一种允许实时检测和标测组织中的空化活动的技术。这个 生物力学模型使用断裂力学来确定组织的粘弹性属性是如何改变的 BWL能量储存在组织中。

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.