NIR Instrument for Singlet Oxygen Mapping during PDT

描述(由申请人提供)：该提案的重点是光动力疗法(PDT)的剂量学领域，特别是乳腺癌的治疗。光敏剂、光通量和氧气这三种PDT成分的最佳剂量对于治疗的成功至关重要。虽然剂量不足会导致癌症复发，但剂量过大可能会导致不良的健康组织损害。一种被广泛接受的精确剂量测定方法是基于这样一个事实，即在PDT过程中局部产生的细胞毒性新生氧量与治疗结果直接相关。近红外漫反射光学层析成像(DOT)已被成功地用于乳腺肿瘤的功能成像，该成像基于乳腺肿瘤与健康组织的内源性和外源性光谱对比度。我们将使用这一成熟的DOT技术，基于光敏剂在光通量下的发光来实时绘制新生氧浓度的空间图谱。在第一阶段，我们将开发一种检测方法来证明光敏剂的时间依赖发光特性与PDT结果直接相关。在第一阶段结果的基础上，我们将在第二阶段开发空间新生氧气成像模块的原型，该模块将通过冷却的多探测器阵列进行并行采集，以实现高分辨率和高通量成像。低成本、紧凑的PDT剂量成像仪模块将被设计成与现有的DOT系统兼容，以扩展它们的应用，在乳癌和其他癌症治疗的PDT期间进行监测。 与公共健康相关：基于光动力疗法(PDT)中使用的药物的时间域特性，漫反射发光成像可用于获得新生氧浓度的定量空间图。乳腺肿块切除术后的PDT是预防癌症局部复发的主要目标应用，目的是改善治疗结果并将副作用降至最低。其他应用可能包括监测脑癌、头颈癌和其他非癌症疾病的PDT治疗期间的剂量评估。

DESCRIPTION (provided by applicant): The focus of the proposal is in the area of dosimetry for photodynamic therapy (PDT), especially for breast cancer treatment. It is crucial that the optimal dosage of the three PDT components - photosensitizer, light fluence, and oxygen - be involved for the successful outcome of the treatment. While under dosing can lead to recurrence of the cancer, over dosing can lead to undesirable healthy-tissue damage. A widely accepted method for accurate dosimetry is based on the fact that the quantity of cytotoxic nascent oxygen generated locally during PDT is directly correlated to the treatment outcome. Diffuse optical tomography (DOT) using near infrared light has been used successfully for functional imaging of breast tumors based on their endogenous and exogenous spectral contrast compared to healthy tissue. We will use this well- established DOT technique to perform real-time spatial mapping of nascent oxygen concentration based on the luminescence from the photosensitizer under light fluence. During Phase I, we will develop a detection methodology to demonstrate that the photosensitizer time dependent luminescence characteristics are directly correlated to PDT outcome. Based on the results of Phase I, we will develop a prototype of the spatial nascent oxygen imaging module during Phase II, which will have parallel acquisition across a cooled multi-detector array for high resolution and high throughput imaging. The low-cost, compact PDT dosimetric imager module will be designed to be compatible with existing DOT systems to extend their applications for monitoring during PDT for breast and other cancer treatments. PUBLIC HEALTH RELEVANCE: Diffuse luminescence imaging can be used to obtain quantitative spatial maps of nascent oxygen concentration based on time domain characteristics of the drugs used in photodynamic therapy (PDT). PDT following breast lumpectomy to prevent local recurrence of cancer is the primary target application, with the goal of improving treatment outcome and minimizing side effects. Other applications could include monitoring for dose evaluation during PDT treatments in brain cancers, head and neck cancers, and other non-cancerous conditions.