In situ PEDSy and light delivery platform for Intracavitory Photodynamic Therapy

用于腔内光动力治疗的原位 PEDSy 和光传输平台

• 批准号: 10266766
• 负责人: Mary Potasek
• 金额: $ 54.2万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-20 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266766
• 关键词: 3-Dimensional; Affect; Anatomy; Calibration; Clinic; Clinical; Clinical Trials; Computer software; Coupled; Data; Deposition; Detection; Development; Devices; Diffuse; Disease; Dose; Feedback; Fiber; Fiber Optics; Fluorescence; Geometry; Goals; Head Cancer; Hour; Human; In Situ; Lasers; Light; Location; Malignant Neoplasms; Measurement; Measures; Medical Device; Mesothelioma; Methods; Modeling; Monitor; Monte Carlo Method; Navigation System; Neck Cancer; Operative Surgical Procedures; Optics; Outcome; PUVA Photochemotherapy; Pathway interactions; Patients; Pharmaceutical Preparations; Photosensitizing Agents; Phototherapy; Physicians; Pleural; Pleural cavity; Pleural photodynamic therapy; Positioning Attribute; Procedures; Process; Property; Research; Series; Shapes; Site; Skin Cancer; Slice; Source; Spatial Distribution; Surface; System; Testing; Therapy Clinical Trials; Therapy trial; Three-Dimensional Imaging; Time; Tissues; Translating; Treatment outcome; Visualization; base; clinical application; clinical efficacy; clinical translation; clinically relevant; curative treatments; design; detector; diffuse reflectance spectroscopy; dosimetry; experimental study; imaging system; in vivo; individual patient; innovation; instrument; interstitial; light dosimetry; new technology; novel; performance tests; personalized medicine; software systems; stem; temporal measurement; therapy outcome; tissue oxygenation; tool; translational study; treatment duration; tumor; uptake

This translational project will develop, evaluate, and clinically test an integrated PDT Explicit Dosimetry System (PEDSy) and light delivery platform for quantitative measurement and delivery of photodynamic therapy (PDT) dose with feedback control. The system will include two key components: hardware for in situ PDT dosimetry and light source tracking in real-time, and software for treatment monitoring of light distribution throughout the pleural cavity during PDT of pleural-involving malignancy. The hardware is composed of a multi-channel instrument that can be used in the clinic during PDT to measure PDT dose generated by the PDT treatment light using the explicit dosimetry of light fluence rate and photosensitizer concentration. Here, the immediate clinical translation is to monitor the PDT dose at multiple sites in patients undergoing pleural PDT for mesothelioma, which has shown significant clinical efficacy in clinical trials to date. Fiber-optic-based fluorescence and diffuse reflectance spectra will also be collected at the same locations to calculate the tissue optical property correction factors for photosensitizer drug concentration. An IR navigation system and a 3D scanner will be developed to track the light source position in real-time as well as determining the geometrical shape of pleural surface for PDT treatment in real-time. The software is composed of a GPU-based Monte Carlo simulation for light fluence rate distribution on the entire pleural cavity coupled with estimation of the PDT dose distribution along the pleural cavity. The outcome of this project will be a novel hardware-software device, PEDSy, that has been optimized and rigorously validated under clinically-relevant conditions. We hypothesize that quantitative modeling of PDT dose deposition by PEDSy will be significantly more predictive of treatment outcome than the current method that employs measurements of light dose without incorporating photosensitizer uptakes. Innovation thereby stems from our unique goal to build a translatable platform for PDT dosimetry that is based on spatial modeling of comprehensive PDT dose, suitable for even sophisticated clinical applications of PDT, and yet generalizable to disease at other anatomic sites, such as head and neck and skin cancers. Moreover, we conceive that this integrated system for clinical PDT can be commercialized shortly after the end of development, and will provide real-time feedback to clinicians for personalization of treatment. Thus, this advanced instrument system is significant because it will open the pathway to dosimetry-based real time individualization of PDT that fully accounts for light and photosensitizer distributions. Lastly, our preliminary data indicate in situ measurements of PDT dose to be a more robust dose metric than the currently used approach which only incorporates light dose deposition. Our proposed platform is thereby expected to impact PDT dosimetry by building a platform that is based on a stronger dose metric (PDT dose) as well as by basing this modeling on its spatial distribution.

这个翻译项目将开发，评估和临床测试综合PDT明确 用于定量测量和交付的剂量测定系统（PEDSY）和轻型输送平台 具有反馈控制的光动力疗法（PDT）剂量。该系统将包括两个密钥 组件：用于原位PDT剂量计和光源跟踪的硬件， 和用于整个胸腔腔内光分布的治疗监测的软件 在胸膜涉及的恶性肿瘤的PDT期间。硬件由多通道组成 可以在PDT期间在诊所中使用的仪器，以测量PDT产生的PDT剂量 使用光通量率和光敏剂的明确剂量测定的处理灯 专注。在这里，直接的临床翻译是在多个以下监测PDT剂量 接受间皮瘤胸膜胸膜PDT患者的部位，该部位显示出明显的 迄今为止，临床试验中的临床功效。基于光纤的荧光和扩散 反射光谱也将在同一位置收集以计算组织光学 光敏剂药物浓度的性质校正因子。红外导航系统和一个 将开发3D扫描仪以实时跟踪光源位置并确定 胸膜表面的几何形状实时用于PDT处理。该软件组成 基于GPU的蒙特卡洛模拟，以在整个胸膜上进行光通量率分布 腔体以及沿胸腔腔的PDT剂量分布的估计。这 该项目的结果将是一种新颖的硬件软件设备Pedsy， 在与临床相关的条件下进行了优化且严格验证。我们假设这一点 PEDSY对PDT剂量沉积的定量建模将显着预测 治疗结果比目前采用光剂量测量的方法 合并光敏剂的摄取。因此，创新源于我们的独特目标 基于综合PDT的空间建模的PDT剂量计的可翻译平台 剂量，甚至适用于PDT的复杂临床应用，但可以推广到 其他解剖部位的疾病，例如头部和颈部和皮肤癌。而且，我们 想象该临床PDT的集成系统可以在结束后不久进行商业化 开发，并将为临床医生提供实时反馈以进行个性化治疗。 因此，该高级仪器系统很重要，因为它将打开通往的途径 基于剂量学的实时实时个性化的PDT，充分说明了光和 光敏剂分布。最后，我们的初步数据表示PDT的原位测量 剂量比当前使用的方法更强大的剂量度量 轻剂量沉积。因此，我们提出的平台预计会影响PDT剂量测定法 通过建立一个基于剂量度量较强的平台（PDT剂量），并通过此基础 建模其空间分布。