Research Project

研究项目

• 批准号: 10707430
• 负责人: Po-Chun Hsu
• 金额: $ 34.61万
• 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/10707430
• 关键词: Adverse event; Affect; American; Artificial Kidney; Behavior; Benign; Cells; Clinical; Collaborations; Communities; Dangerousness; Data Collection; Data Scientist; Dependence; Disease; Doctor of Philosophy; Dose; Dust; Effectiveness; Elements; Engineering; Enhancement Technology; Family suidae; Fiber; Frequencies; Future; Goals; Health Expenditures; Holmium; Hydrogels; In Situ; In Vitro; Injury to Kidney; Kidney; Kidney Calculi; Knowledge; Laser Lithotripsy; Lasers; 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; Resources; Risk; Risk Reduction; Role; Safety; Saline; Science; Stream; Surface; Techniques; Temperature; Thulium; Time; Tissues; Toxic effect; Universities; Urinary Calculi; Urinary tract; Urogenital Diseases; Urology; absorption; calyx structure; cell injury; experience; heat injury; improved; in vivo; metallicity; nanoengineering; nanomaterials; nanoparticle; nanophotonic; nanopolymer; photonics; porcine model; power consumption; programs; renal damage; safety assessment; synergism; theories; 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 尿石疾病（USD）是一种良性但严重疼痛的泌尿生殖器疾病，几乎影响11分之一 美国人，在美国，年度健康支出超过20亿美元。引入高功率/高 频率holmium（HO）：YAG激光器和Thulium纤维激光器（TFL）从根本上改变了 激光岩石疗法（LL），这是美元的选择处理。流行式围绕是一项在决赛中广泛使用的技术 LL的阶段，激光在肾萼中发射，使大量碎片迅速移动以磨碎它们 直到灰尘，这可能导致肾脏的温度显着升高。板凳体外，猪 体内和FDA不良事件报告都引起了人们对危险热剂量积累和 潜在的永久性热损伤。我们最近发表的发现导致我们假设该空穴 气泡崩溃，导致的微射流对石头表面或流式剪切的影响可能有助于 到这个过程。换句话说，流体的激光功率的抽象在弹出中起着至关重要的作用 行为。因此，通过增强HO：YAG激光或TFL滥用，我们可以降低功率要求 产生同等或更强的气泡活动以提高流行式效率，同时降低 肾脏组织热损害的风险。研究项目（RP）的总体目标 杜克向前P20泌尿外科中心将扩大泌尿外科研究中心的研究工作 和杜克大学的工程（治疗） 方法。我们计划利用纳米光学科学来开发具有较高和选择性的专业纳米流体 吸收激光并研究其对LL效率，毒性和临床安全的好处 模型以体外和体内研究。该中心的研究项目具有三个具体目标，重点是（1） 开发具有针对HO：YAG激光（λ=2.1μm）和TFL的精选峰的生物安全纳米颗粒 （λ=1.94μm）和光学比色杯模型中的评估空化动力学和细胞损伤。 （2）调查 基于水凝胶的肾脏模型和检查治疗中纳米颗粒增强的弹出作用 体外有效性和热损伤风险。 （3）在一个 猪模型并评估体内的毒性，安全性和弹出式效率。通过实现这些目标，我们 设想在体外和体内成功的进度和关键的初步数据收集，以支持未来 R01纳米技术增强的应用。我们进一步期待协同和新知识 该远期P20计划创建的将大大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U54中心和Kure K12计划 在杜克大学以及其他美元研究活动。