Research Project

研究项目：摘要 尿石症是一种良性但严重疼痛的泌尿生殖系统疾病，每11人中就有1人患病。 美国人，每年在美国的医疗支出超过20亿美元。高功率/高功率的介绍 频率Ho(Ho)：YAG激光器和TFL从根本上改变了激光器的工作模式 激光碎石术(LL)，这是USD术的首选治疗方法。爆粉是一种在决赛中广泛使用的技术 L1的阶段，在此阶段，激光射入肾盏使相当大的碎片快速移动以研磨它们 降到灰尘，这可能会导致肾脏温度显著升高。体外台式实验，猪 在活体内，和FDA的不良事件报告都引起了对危险热剂量积累和 可能是永久性的热损伤。我们最近发表的研究结果使我们提出了空化的假设 气泡坍塌与微射流冲击石材表面或流动诱导的剪切可能有关。 这一过程。换言之，流体对激光能量的吸收在喷粉过程中起着关键作用。 行为。因此，通过增强Ho：YAG激光器或TFL的吸收，可以降低对激光的功率要求 产生同等或更强的气泡活动，以提高喷粉效率，同时降低 肾脏组织受到热损伤的风险。的研究项目(RP)的总体目标 DUKE FORWARD P20泌尿外科中心是为了扩展泌尿外科研究中心的研究努力 和工程(CURE)在杜克大学通过结合以前未被探索的纳米技术 接近了。我们计划利用纳米光子学来开发一种高选择性的专业纳米流体 在台式试验台上吸收激光并研究其对LL效率、毒性和临床安全性的益处 模型到体外和体内的研究。该中心的研究项目有三个具体目标，重点是(1) 开发对Ho：YAG光(λ=2.1μm)和热释光具有最佳吸收峰的生物安全纳米粒子 (λ=1.94μm)，并在光学试管模型中评估空化动力学和细胞损伤。(2)调查 纳米颗粒增强扬尘在水凝胶肾脏模型中的作用及检测治疗 体外效率和热损伤风险。(3)探讨纳米粒子增强喷粉的效果 在活体内建立猪模型并评估毒性、安全性和除尘效率。通过实现这些目标，我们 展望成功的进展和关键的初步数据收集，无论是在体外还是在体内，以支持未来 R01在纳米技术上的应用-增强型法律援助。我们还预计，协同效应和新知识 由Forward P20计划创建的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，包括哥伦比亚大学的U54中心和Kure K12计划 在杜克大学，以及通过其他联合大学的研究活动。

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.