Research Project

研究项目

基本信息

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
项目类别：
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

项目摘要

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：摘要尿路结石病 (USD) 是一种良性但严重疼痛的泌尿生殖系统疾病，影响近十分之一的人美国人，美国每年的医疗支出超过20亿美元。高功率/高引进。频率钬 (Ho)：YAG 激光器和铥光纤激光器 (TFL) 从根本上改变了激光碎石术 (LL) 是 USD 的首选治疗方法 Pop-dusting 是最终广泛使用的技术。 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将其磨碎变成灰尘，这可能会导致猪体外实验中肾脏温度显着升高。体内和 FDA 不良事件报告都引起了对危险的热剂量积累和我们最近发表的研究结果使我们对这种空化现象提出了挑战。气泡破裂以及由此产生的微射流对石材表面的冲击或流引起的剪切可能有助于换句话说，液体对激光功率的吸收在喷粉过程中起着至关重要的作用。因此，通过增强 Ho:YAG 激光或 TFL 吸收，我们可以降低功率需求。产生同等或更强的气泡活动，以提高喷粉效率，同时降低肾组织热损伤的风险是该研究项目（RP）的总体目标。杜克 FORWARD P20 泌尿外科中心将扩大泌尿外科研究中心的研究工作杜克大学的工程与工程 (CURE)，融合了以前未探索过的纳米技术我们计划利用纳米光子科学开发一种具有高选择性的专用纳米流体。吸收激光并在台式上研究其对 LL 效率、毒性和临床安全性的益处该中心的研究项目有三个具体目标，重点是 (1)。开发生物安全的纳米颗粒，其吸收峰针对 Ho:YAG 激光 (λ = 2.1 μm) 和 TFL 进行了优化 (λ = 1.94 μm) 并评估光学比色皿模型中的空化动力学和细胞损伤 (2) 研究纳米粒子增强的流行喷粉对基于水凝胶的肾脏模型的影响并检查治疗体外效率和热损伤风险 (3) 探索纳米粒子增强的喷粉效果。通过建立猪模型并评估体内毒性、安全性和喷粉效率，我们实现了这些目标。设想体外和体内的成功进展和关键的初步数据收集，以支持未来 R01 在纳米技术增强 LL 上的应用我们进一步预计协同作用和新知识。由 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属于更广泛的 NIDDK CAIRIBU 计划，包括哥伦比亚 U54 中心和 KURe K12 计划在杜克大学，以及通过其他美国研究活动。