A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models

便携式低成本调查点 CapCell 示波器，用于对体外和体内生物模型中的主要代谢轴和相关脉管系统进行成像和量化

• 批准号: 9753458
• 负责人: James V Alvarez
• 金额: $ 54.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753458
• 关键词: Address; Algorithms; Animals; Architecture; Benchmarking; Bioenergetics; Biogenesis; Biological; Biological Assay; Biological Models; Biological Process; Biology; Blood Vessels; Breast Cancer Model; Caliber; Cancer Biology; Cardiovascular system; Cell Line; Cell Respiration; Cells; Characteristics; Citric Acid Cycle; Clinical; Combined Modality Therapy; Communities; Complement; Dark-Field Microscope; Discipline; Disease; Disease model; Down-Regulation; ERBB2 gene; Effectiveness; Exhibits; Fluorescence; Foundations; Frequencies; Genetic Transcription; Genetically Engineered Mouse; Genus Hippocampus; Glucose Transporter; Glycolysis; Goals; Health; Hypoxia; Image; Imagery; Immunohistochemistry; In Vitro; Individual; Investigation; Label; Length; Lighting; Malignant Neoplasms; Mammary gland; Mammospheres; Measures; Metabolic; Metabolism; Methods; Microscope; Microscopy; Mitochondria; Modeling; Mus; Neurosciences; Optics; Organoids; Outcome; Oxidative Phosphorylation; Oxygen; Oxygen Consumption; PECAM1 gene; Pathway interactions; Patients; Pharmacologic Substance; Phenotype; Pimonidazole; Pre-Clinical Model; Process; Publishing; Recurrence; Recurrent disease; Recurrent tumor; Research; Research Personnel; Residual Tumors; Resolution; Rodent; SLC2A1 gene; Sampling; Signal Transduction; Stains; Structure; System; Techniques; Technology; Testing; Tissues; Training; Translating; Translational Research; Tumor-Derived; Vascular Endothelium; Work; Xenograft Model; adduct; anticancer research; cancer imaging; cancer pharmacology; cancer therapy; cell immortalization; chemotherapy; cost; density; extracellular; fluorodeoxyglucose positron emission tomography; glucose uptake; image processing; imaging genetics; imaging system; immortalized cell; improved; in vitro Model; in vivo; in vivo Model; insight; interest; malignant breast neoplasm; metabolic abnormality assessment; metabolic imaging; metabolomics; neoplastic cell; novel; portability; programs; quantitative imaging; therapy outcome; tool; trend; tumor; user-friendly; whole body imaging

Summary Interest in metabolism and the vascular microenvironment continues to grow in a broad range of disciplines including neuroscience, cardiovascular biology, and the field of cancer research. Given their clinical importance, there are surprisingly few techniques available that can provide a systems-level view of these hallmarks together in vivo. Though there are many bench-top microscopes and metabolic tools available to provide exquisite resolution and contrast for metabolic or vascular imaging, they often require researchers to transport animals to specialized facilities and this limits access for high frequency imaging, these systems require extensive training and often have fields of view (FOV), resolution and wavelengths that fits only the most common use cases (in the case of optical microscopy systems). Our goals are to develop and validate a point-of-investigation metabolic and vascular imaging system and corresponding algorithms that will democratize access to imaging for cancer research in individual cancer pharmacology labs. The capabilities of our system will be demonstrated through imaging of metabolism, vascular function, and architecture at a spatial resolution that can visualize proliferative, regressive, residual, and recurrent disease in a breast cancer model. Our technique could provide a comprehensive understanding how the metabolic characteristics of tumors impact therapeutic outcome and can be used in a wide range of cancer pharmacology applications to improve the effectiveness of cancer therapy. The specific goals of this proposal are to develop an low-cost, portable, user friendly, CapCell scope to image key metabolic and vascular endpoints simultaneously with a wide range of FOVs and resolutions (Aim 1), demonstrate that this technology provides comparable information and can complement established methods in well-established murine tumor models of breast cancer (Aim 2), and validate the technology on GEM model derived mammospheres and in vivo mammary window models of GEM model derived tumors (Aim 3). This proposal sets the foundation for translating our technology to patient-derived xenograft (PDX) models and patient-derived organoids, which have been shown to be able to faithfully recapitulate many of the micro-environmental features of patient tumors, allowing us move our technique forward towards translational pharmaceutical research.

概括 对新陈代谢和血管微环境的兴趣继续在广泛的学科中增长 包括神经科学，心血管生物学和癌症研究领域。考虑到它们的临床重要性， 令人惊讶的是，很少有技术可以在其中提供这些标志的系统级别的视图 体内。尽管有许多基准显微镜和代谢工具可提供精美的分辨率 以及代谢或血管成像的对比，它们通常要求研究人员将动物运输到专业 设施和此限制了高频成像的访问，这些系统需要大量的培训，并且经常有 视野（FOV），分辨率和波长仅适合最常见的用例（在光学的情况下 显微镜系统）。我们的目标是开发和验证调查点的代谢和血管成像 系统和相应的算法，将民主化单个癌症研究成像的访问 癌症药理学实验室。我们系统的能力将通过代谢成像来证明 血管功能和以空间分辨率的体系结构可以看到增殖，回归，残留和 乳腺癌模型中的复发性疾病。我们的技术可以提供全面的理解 肿瘤的代谢特征会影响治疗结果，可在广泛的癌症中使用 提高癌症治疗有效性的药理学应用。该提议的具体目标是 开发低成本，便携式，用户友好的Capcell范围，以图像关键代谢和血管终点 同时与广泛的FOV和决议（AIM 1）一起证明了该技术提供的 可比较的信息，可以补充已建立的鼠类肿瘤模型中已建立的方法 乳腺癌（AIM 2），并在GEM模型中验证该技术衍生乳腺和体内乳腺 宝石模型衍生肿瘤的窗户模型（AIM 3）。该提案为翻译我们的基础奠定了基础 患者衍生的异种移植（PDX）模型和患者衍生的类器官的技术，已被证明为 能够忠实地概括患者肿瘤的许多微环境特征，使我们移动 转向转化制药研究的技术。