Research Project

研究项目

• 批准号: 10596709
• 负责人: Po-Chun Hsu
• 金额: $ 34.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596709
• 关键词: Adverse event; Affect; American; Artificial Kidney; Behavior; Benign; Cells; Clinical; Collaborations; Communities; Consumption; Dangerousness; Data Collection; Data Scientist; Dependence; Disease; Doctor of Philosophy; Dose; Dust; Effectiveness; Elements; Engineering; Family suidae; Fiber; Frequencies; Future; Goals; Health Expenditures; Holmium; Hydrogels; In Situ; In Vitro; Information Resources; Injury to Kidney; Kidney; Kidney Calculi; Knowledge; Laser Lithotripsy; Lasers; Lead; Liquid substance; Mentored Clinical Scientist Development Program; Modeling; Nanotechnology; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Optics; Pain; Physiologic pulse; Pilot Projects; Play; Polymers; Positioning Attribute; Procedures; Process; Property; Publishing; Reporting; Research; Research Activity; Research Infrastructure; Research Personnel; Research Project Grants; Risk; Role; Safety; Saline; Science; Stream; Surface; Techniques; Temperature; Thulium; Tissues; Toxic effect; Universities; Urinary Calculi; Urinary tract; Urogenital Diseases; Urology; absorption; base; calyx structure; cell injury; experience; heat injury; improved; in vivo; metallicity; nanoengineering; nanomaterials; nanoparticle; nanophotonic; photonics; porcine model; programs; renal damage; synergism; theories; time use; treatment choice; urologic

RESEARCH PROJECT: ABSTRACT Urinary stone disease (USD) is a benign but severely painful genitourinary disease that affects nearly 1 in 11 Americans, with an annual health expenditure of over $2 billion in the US. The introduction of high power/high frequency Holmium (Ho): YAG lasers and Thulium Fiber Laser (TFL) have fundamentally altered the mode of laser lithotripsy (LL), which is the treatment of choice for USD. Pop-dusting is a technique widely used in the final stage of LL, whereby the laser fired in a renal calyx causes the sizable fragments to move rapidly to grind them down to dust, which potentially leads to significant temperature increase in the kidney. Benchtop in vitro, porcine in vivo, and FDA adverse event reports all raise concerns for dangerous thermal dose accumulation and potentially permanent thermal injury. Our recently published findings lead us to hypothesize that cavitation bubble collapse with resultant microjet impact on the stone surface or streaming-induced shear may contribute to this process. In other words, the absorption of laser power of the fluid plays a critical role in the pop-dusting behavior. Therefore, by enhancing the Ho:YAG laser or TFL absorption, we can lower the power requirement for generating equivalent or stronger bubble activities to improve pop-dusting efficiency, while concurrently lowering the risk of thermal damage to the kidney tissue. The overarching objective of the Research Project (RP) of the Duke FORWARD P20 Urology Center is to extend the research efforts of the Center for Urological Research and Engineering (CURE) at Duke University by incorporating previously unexplored nanotechnology approaches. We plan to utilize nanophotonic science to develop a specialized nanofluid with high and selective absorption of the laser and investigate its benefits on LL efficiency, toxicity, and clinical safety from a benchtop model to in vitro and in vivo studies. The center's Research Project has three Specific Aims focusing on (1) Develop biologically safe nanoparticles with absorption peak optimized for Ho:YAG laser (λ = 2.1 μm) and TFL (λ = 1.94 μm) and assess cavitation dynamics and cell injury in an optical cuvette model. (2) Investigate the effects of nanoparticle-enhanced pop-dusting in a hydrogel-based kidney model and examine treatment efficiency and thermal damage risk in vitro. (3) Explore the effects of nanoparticle-enhanced pop-dusting in a porcine model and evaluate toxicity, safety, and pop-dusting efficiency in vivo. By achieving these aims, we envision successful progress and critical preliminary data collection, both in vitro and in vivo, for supporting future R01 applications on nanotechnology-enhanced LL. We further anticipate that the synergy and new knowledge created by this FORWARD P20 program will greatly enhance and promote our existing and future collaborations within the broader NIDDK CAIRIBU program, including the U54 Center at Columbia and the KURe K12 program at Duke, as well as through other USD research activities.

研究项目：摘要 泌尿系结石病（USD）是一种良性但严重疼痛的泌尿生殖系统疾病，影响近1/11 美国人，美国每年的医疗支出超过20亿美元。高功率/高功率的介绍 频率钬（Ho）：YAG激光器和钍光纤激光器（TFL）从根本上改变了 激光碎石术（LL），这是USD的首选治疗方法。喷粉是一种在决赛中广泛使用的技术 LL阶段，在肾盏中发射的激光导致相当大的碎片快速移动以研磨它们 降到尘埃，这可能导致肾脏温度显著升高。体外实验台，猪 体内试验和FDA不良事件报告都提出了对危险热剂量累积的担忧， 潜在的永久性热损伤。我们最近发表的研究结果使我们假设， 气泡破裂和由此产生的微射流对结石表面的冲击或流致剪切可能有助于 这个过程。换句话说，流体对激光功率的吸收在爆尘中起着关键作用 行为因此，通过增强Ho：YAG激光器或TFL吸收，我们可以降低功率要求 产生等同或更强的气泡活动以提高爆破除尘效率，同时降低 肾脏组织热损伤的风险。研究项目的总体目标（RP） 杜克FORWARD P20泌尿外科中心将扩展泌尿外科研究中心的研究工作 杜克大学的纳米技术与工程学院（CURE） 接近。我们计划利用纳米光子科学来开发一种具有高选择性的专用纳米流体。 吸收激光，并从实验台上研究其对LL效率、毒性和临床安全性的益处 用于体外和体内研究。该中心的研究项目有三个具体目标，重点是（1） 开发具有针对Ho：YAG激光（λ = 2.1 μm）和TFL优化的吸收峰的生物安全纳米颗粒 （λ = 1.94 μm），并在光学比色皿模型中评估空化动力学和细胞损伤。(2)探讨 纳米颗粒增强的pop-dusting在基于水凝胶的肾脏模型中的作用和检查治疗 效率和热损伤风险。(3)探索纳米颗粒增强的流行除尘在一个 猪模型，并评估体内毒性，安全性和爆尘效率。通过实现这些目标，我们 设想成功的进展和关键的初步数据收集，无论是在体外和体内，以支持未来 R 01应用于纳米技术增强LL。我们进一步预计，协同作用和新知识 由该FORWARD P20计划创建的项目将极大地增强和促进我们现有和未来的合作 在更广泛的NIDDK CAIRIBU计划中，包括哥伦比亚的U 54中心和KURe K12计划 在杜克，以及通过其他美元的研究活动。