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.

总结 对代谢和血管微环境的兴趣在广泛的学科中持续增长 包括神经科学、心血管生物学和癌症研究领域。鉴于其临床重要性， 令人惊讶的是，很少有技术可以提供这些特征的系统级视图， vivo.虽然有许多台式显微镜和代谢工具可提供精致的分辨率 以及用于代谢或血管成像的造影剂，它们通常需要研究人员将动物运送到专门的 这些系统需要大量的培训，并且通常需要 视场（FOV）、分辨率和波长仅适用于最常见的用例（在光学的情况下）。 显微镜系统）。我们的目标是开发和验证一个点的调查代谢和血管成像 本发明提供了一种将使个体癌症研究中成像访问民主化的系统和相应算法 癌症药理学实验室我们系统的能力将通过新陈代谢成像来证明， 血管功能和结构的空间分辨率，可以可视化增殖，退化，残留， 乳腺癌模型中的复发性疾病。我们的技术可以提供一个全面的理解， 肿瘤的代谢特征影响治疗结果，可用于广泛的癌症 药理学应用，以提高癌症治疗的有效性。该提案的具体目标是 开发一种低成本、便携式、用户友好型CapCell内窥镜，用于对关键代谢和血管终点进行成像 同时具有广泛的FOV和分辨率（目标1），证明该技术提供了 具有可比的信息，可以补充完善的小鼠肿瘤模型中已建立的方法， 乳腺癌（目标2），并验证GEM模型衍生的乳腺球和体内乳腺癌的技术 GEM模型衍生肿瘤的窗口模型（Aim 3）。这一建议为翻译我们的 患者来源的异种移植物（PDX）模型和患者来源的类器官，已被证明是 能够忠实地概括患者肿瘤的许多微环境特征，使我们能够移动我们的 技术向转化药物研究迈进。