BWL Interaction with Kidney Tissue

BWL 与肾脏组织的相互作用

• 批准号: 10452584
• 负责人: JAMES C WILLIAMS
• 金额: $ 35.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452584
• 关键词: Acoustics; Acute; Animal Model; Apatites; Biomechanics; Coupled; Data; Deposition; Detection; Disease; Documentation; Dose; Duct (organ) structure; Effectiveness; Endoscopy; Evolution; Excision; Feedback; Fracture; Gel; Health; Human; In Situ; In Vitro; Injury; Injury to Kidney; Kidney; Kidney Calculi; Kidney Papilla; Lead; Learning; Link; Lithotripsy; Maps; Measures; Mechanics; Mediating; Minerals; Minor; Modeling; Monitor; Morphology; Patients; Physicians' Offices; Process; Property; Protocols documentation; Renal Tissue; Renal function; Resistance; Safety; Science; Shock; Structure; System; Techniques; Technology; Testing; Time; Tissue Model; Tissues; Ultrasonic Therapy; Ultrasonics; Urinary Calculi; Visual; Work; X-Ray Computed Tomography; base; biomechanical model; calcification; design; experimental study; in vitro Model; in vitro testing; interstitial; mathematical model; microCT; particle; porcine model; renal damage; response; sound; tissue injury; treatment strategy; ultrasound; viscoelasticity

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.

项目摘要/摘要 - 项目3 爆发波碎石（BWL）是一种基于新兴的超声技术，显示出能够销毁的希望 肾结石在实物办公室的环境中。项目3将重点关注BWL的研究 带有实际人类石头和组织的BWL声能。我们的项目在研究人类方面是独一无二的 患者，动物模型，离体肾脏和体外模型，均由数学建模支持。在AIM 1中，我们将 在人类观察到用BWL破坏石头并监测BWL对肾组织的影响的行为，测试 假设BWL会在人类肾脏中打破石头，而不会对肾脏组织造成重大损害。在这个 AIM，项目3将与项目1合作，以直接验证BWL在人肾脏中破裂的石头，并且 类似地研究BWL对组织的可见作用，或者不增加自适应反馈控制 用于空化。石材破裂和组织健康的视觉文献将使用最新的内窥镜检查 和石材分析技术。在AIM 2中，我们将在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，检验了以下假设： 不会导致BWL损坏增加。使用体外测试系统将实现此目标 材料将连接到模拟凝胶中或嵌入与肾脏相关的计算中的模型 乳头，并使用微CT成像定量结果。所有这些实验将与 通过弗洛德实验室进行建模，使总体结果不仅仅是经验，但设计为更深层次 将了解BWL声能在石材组织组织中的作用机理的理解。在AIM 3中， 我们将通过测量与肾脏形态的变化和功能相关的变化来评估BWL的肾脏影响 生物猪模型中的经皮BWL处理，检验了以下假设。 哪些BWL既安全又高效，可以使用提供保护的预处理策略来扩展 肾脏组织。猪模型将用于测量BWL对肾脏结构和功能的影响 能量剂量以上和低于阈值，以诱导与损伤有关的超声可见的空化。安全 更改BWL及向上的应用也将进行测试。与SW一起使用的保护协议（例如，预处理 暂停）将测试对BWL肾脏反应的影响。在AIM 4中，我们将评估BWL期间的组织健康 在体内灌注肾脏系统中的声学排放和组织损伤的生物力学模型，测试 假设可以使用空化，偶联到生物力学组织模型的声学发射来监测 BWL期间组织的健康，并提供实时反馈，以避免或最大程度地减少附带组织损伤。被动声学 映射（PAM）是一种允许实时检测并在组织中映射的空化活动的技术。 生物力学模型采用断裂力学来确定组织的粘弹性如何改变为 BWL能量沉积在组织中。