Optical Dosimeter-guided Photodynamic Therapy

光动力疗法（PDT）是一种很有前途的癌症治疗方法。中的氧分子 亚稳态单重态δ O2（1Δ）被认为是在肿瘤发生过程中破坏癌细胞的物质。 PDT。尽管靶向PDT的益处是选择性地杀死肿瘤，对周围环境的影响最小， 健康组织，目前很难，如果不是不可能的话，预测个体对 PDT。这抑制了PDT用于临床用途的接受。在NCI SBIR资助下， Sciences Inc. (PSI)已经开发了两个原型，在体内能够PDT剂量计：一个非成像超， 基于光电倍增管（PMT）的点传感器，用于单线态O2检测和2D成像传感器 用于PS荧光和单线态O2检测。这些设备使用光谱和时间辨别 优化灵敏度的方法我们提出的计划的总体目标是产生一个综合， 成像PDT系统，其将使用实时反馈来控制治疗期间的PDT光剂量。 在第一阶段，我们将开发和测试新推出的2D成像相机，该相机包含以下门控功能 微秒和快速帧速率。这将使单线态氧的灵敏度提高至少一个数量级 数量级。该系统将基于PSI的2D成像系统的当前系统平台， 已经证明了观察PDT过程中产生的体内单线态O2和PS荧光的能力。的 当前系统使用近红外（NIR）敏感相机来获取单态O2图像。然而，这台相机 没有快速的时间选通能力，这将检测方法限制为仅光谱 歧视该系统将在PSI的体外样本上进行开发和测试，然后运输到 达特茅斯学院进行体内试验。I期研究结果将用于设计II期系统 用于PDT治疗和剂量计。一个光纤耦合的脉冲二极管激光器将用于光动力治疗 激励源I期研究的目标是证明新的检测灵敏度。 在PSI检测系统中集成了2D摄像头。在第二阶段，联合PDT系统将 设计、制造和测试用于体外和体内研究的广泛性能验证。一个 精确的剂量计，以优化个人治疗反应的PDT是必要的，以提高 PDT在临床环境中的效果。一个完全开发的仪器将是一个宝贵的工具，首先为光动力疗法 研究人员和随后的临床PDT用途。

Photodynamic Therapy (PDT) is a promising modality for cancer treatment. Oxygen molecules in the metastable singlet delta state O2(1Δ) are believed to be the species that destroys cancerous cells during PDT. Despite the benefit of targeted PDT that kills tumors selectively with minimum effect on surrounding healthy tissues, at the present time it is difficult, if not impossible, to predict the response of an individual to PDT. This has inhibited the acceptance of PDT for clinical uses. Under NCI SBIR funding, Physical Sciences Inc. (PSI) has developed two prototype, in vivo capable dosimeters for PDT: a non-imaging ultra- sensitive photomultiplier tube (PMT)-based point sensor for singlet O2 detection and a 2D imaging sensor for PS fluorescence and singlet O2 detections. These devices use spectral and temporal discrimination methods to optimize sensitivity. The overall goal of our proposed program is to produce an integrated, imaging PDT system that will use real-time feedback to control PDT light dose during the treatment. In Phase I, we will develop and test a newly introduced 2D imaging camera that incorporates gating below a microsecond and a fast framing rate. This will enhance the sensitivity singlet oxygen by at least an order of magnitude. The system will be based upon PSI's current system platform of the 2D imaging system that has demonstrated the ability to observe singlet O2 and PS fluorescence in vivo produced during PDT. The current system uses a near infrared (NIR) sensitive camera for singlet O2 images. However, this camera does not have a fast time-gating capability, and that limits the detection method to only spectral discrimination. The system will be developed and tested on in vitro samples at PSI then transported to Dartmouth College for in vivo testing. The Phase I study result will be utilized to design a Phase II system for both PDT treatments and dosimeters. A fiber-coupled pulsed diode laser will be used for the PDT excitation source. The goal of the Phase I study is to demonstrate the detection sensitivity of the newly introduced 2D camera integrated in the PSI detection system. In Phase II the combined PDT system will be designed, built, and tested for extensive performance verification for in vitro and in vivo studies. An accurate dosimeter to optimize the individual treatment response of PDT is necessary to improve the outcomes of PDT in a clinical environment. A fully developed instrument will be a valuable tool first for PDT researchers and subsequently for clinical PDT uses.