In situ PEDSy and light delivery platform for Intracavitory Photodynamic Therapy

这个翻译项目将开发，评估和临床测试一个综合的PDT显式 剂量测定系统（PEDSy）和光传输平台，用于定量测量和传输 光动力治疗（PDT）剂量反馈控制。该系统将包括两个关键 组件：用于原位PDT剂量测定和光源实时跟踪的硬件， 以及用于整个胸膜腔的光分布的治疗监测的软件 在涉及胸膜的恶性肿瘤的PDT期间。硬件由多通道 在PDT过程中可用于临床的仪器，用于测量PDT产生的PDT剂量 使用光通量率和光敏剂的显式剂量测定法的治疗光 浓度.在这里，直接的临床翻译是监测PDT剂量在多个 在接受胸膜PDT治疗间皮瘤的患者中， 迄今为止临床试验的临床疗效。基于光纤的荧光和漫射 还将在相同的位置收集反射光谱 光敏剂药物浓度的性质校正因子。红外导航系统和 将开发3D扫描仪，以实时跟踪光源位置并确定 用于实时PDT治疗的胸膜表面的几何形状。该软件由 基于GPU的蒙特卡罗模拟，用于整个胸膜上的光通量率分布 与沿沿着胸膜腔的PDT剂量分布的估计相结合。的 该项目的成果将是一个新的硬件软件设备，PEDSy，已经 在临床相关条件下进行了优化和严格验证。我们假设 通过PEDSy的PDT剂量沉积的定量建模将显著更能预测 治疗结果比目前的方法，采用光剂量的测量， 掺入光敏剂摄取。因此，创新源于我们的独特目标，即建立一个 基于综合PDT空间建模的PDT剂量测定可平移平台 剂量，适用于甚至复杂的PDT临床应用，但可推广到 其他解剖部位的疾病，如头颈癌和皮肤癌。而且我们 设想这种用于临床PDT的集成系统可以在结束后不久商业化， 并将为临床医生提供实时反馈，以进行个性化治疗。 因此，这种先进的仪器系统是重要的，因为它将打开通往 基于剂量测定的PDT的真实的时间个体化，其完全考虑光和 光敏剂分布最后，我们的初步数据表明，在原位测量PDT 剂量是比目前使用的方法更稳健的剂量度量， 光剂量沉积。因此，我们提出的平台预计将影响PDT剂量测定 通过建立一个基于更强剂量度量（PDT剂量）的平台， 模拟其空间分布。

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.