Core C: In vivo Imaging, Dosimetry and Sensing of Photodynamic-Immune Responses and Synergies

核心 C：光动力免疫反应和协同作用的体内成像、剂量测定和传感

• 批准号: 10705166
• 负责人: Brian W. Pogue
• 金额: $ 21.26万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705166
• 关键词: Aftercare; Algorithms; Automobile Driving; Biochemical; Biological; Biological Assay; Biological Response Modifier Therapy; Biophysics; Blood capillaries; Cells; Cellular Infiltrate; Cellular Phone; Chemotherapy and/or radiation; Clinic; Clinical; Collaborations; Collagen; Combined Modality Therapy; Complex; Data; Dermatologic; Dermatology; Edema; Endoscopic Ultrasonography; Extracellular Matrix; Feedback; Fiber; Fluorescence; Fresh Tissue; Goals; Human; Image; Imaging Device; Immune; Immune response; Immune signaling; Immune system; Immunotherapy; In Situ; Individual; Inflammation; Invaded; Legal patent; Lesion; Light; Lymphocyte Activation; Lymphocytic Infiltrate; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Molecular; Operative Surgical Procedures; Optics; Oxygen; PET/CT scan; Pancreatic Adenocarcinoma; Perfusion; Photosensitizing Agents; Physiological; Positron-Emission Tomography; Pre-Clinical Model; Production; Prognosis; Sampling; Scanning; Services; Signal Transduction; Singlet Oxygen; Surface; Surrogate Markers; System; T-Cell Activation; Technology; Testing; Texture; Time; Tissues; Translating; Validation; Variant; Visualization; Work; X-Ray Computed Tomography; angiogenesis; cancer imaging; cancer infiltrating T cells; clinical imaging; clinical translation; contrast enhanced computed tomography; cost; dosimetry; elastography; fluorescence imaging; image guided; immune activation; in vivo; in vivo imaging; indexing; individualized medicine; innovation; invention; molecular marker; pre-clinical; preclinical study; radiomics; recruit; response; response biomarker; synergism; technological innovation; technology development; tissue mapping; tool; translational potential; tumor; usability

ABSTRACT The central goal of the core to service the projects with measurement tools that they can use to control the individualization of treatment, and while they may be imperfect markers, they can provide guidance as to the optimal way to have synergistic combination treatments. The individual physiologic variation in immune response and PDT are both known to be at least as variable as responses from traditional broadband therapies such as surgery, chemotherapy or radiation. This core develops technologies and imaging tools that provide either direct measurement of dosimetry or surrogate biomarkers of response that would have clinical translation potential. These tools will be able to help: i) control PDT dosimetry; ii) sample for physio-biologic tissue responses, and iii) predict for synergy between PDT and immunotherapies. The work with Project 1 in dermatology focuses on Imaging PDT dosimetry by measuring the 3 core parameters of PDT, including: (i) oxygen, (ii) photosensitizer, and (iii) light, and surrogates and combinations of these. Imaging Oxygen from inherent PpIX delayed fluorescence was demonstrated here the first time. This tool will be optimized and developed into a controlled handheld tool for experimental deployment in the clinic. PpIX dosimetry innovation has advanced to allow cellphone measurement of levels, and is deployed at all clinics with low cost and high usability. Immune invasion and response imaging are exceptionally hard to visualize, but tools to provide surrogates of this are explored. In Project 2, pancreatic adenocarcinoma PDT and PDP Response Imaging is continued with analysis of CT scans and Endoscopic Ultrasound (EUS). Established studies of tissue stiffness mapping with EUS elastography and CT changes are used and imaging surrogate biomarkers of PDP effect by Radiomics has been completed, and a Radiomic index hypothesized. In Project 3, preclinical tissue stiffness & collagen mapping in situ are developed by UV fluorescence imaging of fresh tissue. This system will be used to iteratively determine how PDP changes in PDAC can be related to the definition of a quantitative Radiomic index. The Core develops tools for these projects and provides guidance on technology innovation and development as these are iterated on.

摘要 核心的中心目标是使用测量工具为项目提供服务，这些测量工具可用于控制 个体化治疗，虽然它们可能是不完美的标志，但它们可以为 进行协同联合治疗的最佳方式。免疫反应中的个体生理差异 和PDT都已知至少与传统宽带疗法的反应一样可变，如 手术、化疗或放射治疗。该核心开发的技术和成像工具可直接提供 将具有临床翻译潜力的反应的剂量学或替代生物标志物的测量。 这些工具将能够帮助：i)控制PDT剂量测定；ii)生理-生物组织反应的样本；以及iii) 预测光动力疗法和免疫疗法之间的协同作用。皮肤科项目1的工作重点是 通过测量PDT的3个核心参数来成像PDT剂量学，包括：(I)氧，(Ii)光敏剂， 和(Iii)光，以及这些的替代品和组合。从固有的PPIX延迟成像氧气 第一次在这里展示了荧光。该工具将被优化并发展为受控的 用于临床实验部署的手持工具。PPIX剂量学创新已经进步到允许 手机测量水平，并部署在所有诊所以低成本和高可用性。免疫侵袭 和反应成像是特别难可视化的，但提供这方面的替代工具是探索的。在……里面 项目2，胰腺癌PDT和PDP反应成像继续进行CT扫描分析 和内窥镜超声(EUS)。已建立的EUS弹性成像组织硬度标测研究 使用CT改变，并已完成放射组学PDP效应的成像替代生物标志物，以及 一种假定的辐射指数。在项目3中，进行了临床前组织硬度和胶原蛋白原位标测 通过对新鲜组织进行紫外荧光成像。该系统将用于反复确定PDP如何变化 在PDAC中可以定义一个定量的放射体学指数。核心为这些开发工具 项目，并提供关于技术创新和开发的指导，因为这些都是迭代的。