In situ PEDSy and light delivery platform for Intracavitory Photodynamic Therapy

该翻译项目将开发、评估和临床测试集成的PDT显式 用于定量测量和传输的剂量测量系统(PEDSy)和光传输平台 光动力疗法(PDT)剂量反馈控制。该系统将包括两个密钥 组件：用于现场PDT剂量测量和光源实时跟踪的硬件， 以及用于治疗监测整个胸腔的光分布的软件 在累及胸膜的恶性肿瘤的PDT中。硬件由多通道组成 临床上可用于光动力疗法中测量光动力疗法产生的光动力疗法剂量的仪器 用光通量率和光敏剂的显式剂量法治疗光 集中精神。在这里，直接的临床翻译是监测PDT剂量在多个 间皮瘤接受胸膜PDT治疗的患者的部位，已显示出显著的 到目前为止的临床试验的临床疗效。光纤荧光和漫反射 还将在相同的位置收集反射光谱，以计算组织光学 光敏剂药物浓度的性质修正系数。一种红外导航系统和一种 将开发3D扫描仪来实时跟踪光源位置并确定 用于PDT治疗的胸膜表面几何形状的实时显示。该软件是由 基于GPU的全胸膜光通量分布的蒙特卡罗模拟 结合胸腔内PDT剂量沿胸腔分布的估算。这个 该项目的成果将是一种新的硬件-软件设备，PEDSy，它已经被 在临床相关条件下进行了优化和严格验证。我们假设 PEDSy对PDT剂量沉积的定量模拟将显著更好地预测 治疗结果比目前的方法，使用测量光剂量没有 加入光敏剂。因此，创新源于我们的独特目标，即建设 基于综合PDT空间建模的可平移PDT剂量测量平台 剂量，适用于PDT的甚至复杂的临床应用，但可推广到 其他解剖部位的疾病，如头颈部和皮肤癌。此外，我们 设想这种临床PDT的集成系统在结束后不久就可以商业化 并将向临床医生提供实时反馈，以便进行个性化治疗。 因此，这一先进的仪器系统具有重要意义，因为它将为 基于剂量学的PDT实时个性化，充分考虑了光线和 光敏剂分布。最后，我们的初步数据表明，在现场测量的PDT 剂量是一种比目前使用的方法更可靠的剂量度量，目前使用的方法只包括 光剂量沉积。因此，我们提出的平台有望对PDT剂量学产生影响 通过构建基于更强的剂量度量(PDT剂量)的平台，以及基于此 对其空间分布进行建模。

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.