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: 10494490
• 负责人: Brian W. Pogue
• 金额: $ 20.14万
• 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/10494490
• 关键词: Aftercare; Algorithms; Automobile Driving; Biochemical; Biological; Biological Assay; Biological Response Modifier Therapy; Biophysics; Blood capillaries; Cells; Chemotherapy and/or radiation; Clinic; Clinical; Collaborations; Collagen; Complex; Data; Dermatologic; Dermatology; Development; 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; Infiltration; Inflammation; Legal patent; Lesion; Leucocytic infiltrate; Light; Lymphocyte; 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; Recruitment Activity; Sampling; Scanning; Services; Signal Transduction; Singlet Oxygen; Surface; Surrogate Markers; System; T-Cell Activation; Technology; Testing; Texture; Time; Tissues; Translating; Translations; Validation; Variant; Work; X-Ray Computed Tomography; base; cancer imaging; 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; molecular marker; pre-clinical; preclinical study; radiomics; response; response biomarker; synergism; tissue mapping; tool; 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 核心的中心目标是为项目提供测量工具，他们可以使用这些工具来控制 个体化治疗，虽然他们可能是不完美的标志物，他们可以提供指导， 最佳的方式有协同组合治疗。免疫反应的个体生理差异 和PDT都已知至少与传统宽带疗法的反应一样可变， 手术、化疗或放疗。该核心开发技术和成像工具，提供直接 具有临床转化潜力的剂量测定或替代反应生物标志物的测量。 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PDT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，包括：（i）氧，（ii）光敏剂， 和（iii）光，以及这些的替代物和组合。来自固有PpIX的成像氧延迟 荧光在此首次得到证实。这一工具将得到优化，并发展成为一个可控的 用于临床实验部署的手持工具。PpIX剂量测定创新已经取得进展， 手机测量水平，并部署在所有诊所，成本低，可用性高。免疫侵袭 和反应成像是非常难以想象的，但工具，以提供代理人，这是探索。在 项目2，胰腺癌PDT和PDP响应成像继续进行CT扫描分析 内镜超声（Endoscopic Ultrasound，EUS）EUS弹性成像组织硬度标测的既定研究， 使用CT变化，并已完成放射组学PDP效应的成像替代生物标志物， a假设的放射组学指数。在项目3中，开发了临床前组织硬度和原位胶原映射 通过新鲜组织的紫外荧光成像。该系统将用于反复确定PDP如何变化 在PDAC中，可以与定量放射组学指数的定义相关。核心为这些开发工具 项目，并提供技术创新和发展的指导，因为这些都是迭代。