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: 10320839
• 负责人: James V Alvarez
• 金额: $ 56.53万
• 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/10320839
• 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; Immunohistochemistry; In Vitro; Individual; Investigation; Label; Length; Lighting; Malignant Neoplasms; 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; Visualization; Work; adduct; anticancer research; automated segmentation; cancer imaging; cancer pharmacology; cancer therapy; cell immortalization; chemotherapy; cost; density; extracellular; fluorodeoxyglucose positron emission tomography; glucose uptake; image processing; imaging genetics; imaging system; improved; in vitro Model; in vivo; in vivo Model; insight; interest; malignant breast neoplasm; mammary; metabolic abnormality assessment; metabolic imaging; metabolomics; neoplastic cell; novel; patient derived xenograft model; portability; programs; quantitative imaging; segmentation algorithm; 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 许多学科对新陈代谢和血管微环境的兴趣持续增长 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，很少有可用的技术可以同时提供这些特征的系统级视图。 体内。尽管有许多台式显微镜和代谢工具可提供精致的分辨率 以及代谢或血管成像的对比，它们通常需要研究人员将动物运送到专门的场所 设施，这限制了高频成像的访问，这些系统需要大量的培训，并且通常具有 视场 (FOV)、分辨率和波长仅适合最常见的用例（在光学器件的情况下） 显微镜系统）。我们的目标是开发和验证研究点代谢和血管成像 系统和相应的算法将使个体癌症研究成像的获取民主化 癌症药理学实验室。我们系统的功能将通过新陈代谢成像来证明， 空间分辨率下的血管功能和结构，可以可视化增殖、回归、残余和 乳腺癌模型中的复发性疾病。我们的技术可以提供全面的了解 肿瘤的代谢特征影响治疗结果，可用于多种癌症 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 开发低成本、便携式、用户友好的 CapCell 示波器，用于对关键代谢和血管终点进行成像 同时具有广泛的视场和分辨率（目标 1），证明该技术提供 可比较的信息，可以补充已建立的小鼠肿瘤模型中的既定方法 乳腺癌（目标2），并验证GEM模型衍生乳腺球和体内乳腺技术 GEM 模型衍生肿瘤的窗口模型（目标 3）。该提案为翻译我们的 技术应用于患者来源的异种移植（PDX）模型和患者来源的类器官，已被证明 能够忠实地再现患者肿瘤的许多微环境特征，使我们能够移动我们的 转化药物研究的技术进步。

项目成果

Understanding the sources of errors in ex vivo Hsp90 molecular imaging for rapid-on-site breast cancer diagnosis.

了解用于快速现场乳腺癌诊断的离体 Hsp90 分子成像的错误来源。

• 发表时间: 2021-04-01
• 影响因子: 3.4
• 作者: Wang, Roujia;Alvarez, Daniel A;Crouch, Brian T;Pilani, Aditi;Lam, Christopher;Zhu, Caigang;Hughes, Philip;Katz, David;Haystead, Timothy;Ramanujam, Nirmala
• 通讯作者: Ramanujam, Nirmala

Metabolic Imaging as a Tool to Characterize Chemoresistance and Guide Therapy in Triple-Negative Breast Cancer (TNBC).

代谢成像作为表征三阴性乳腺癌 (TNBC) 化疗耐药性和指导治疗的工具。

• 发表时间: 2023-10-02
• 作者: Sunassee, Enakshi D;Jardim;Madonna, Megan C;Ordway, Bryce;Ramanujam, Nirmala
• 通讯作者: Ramanujam, Nirmala

A color-based tumor segmentation method for clinical ex vivo breast tissue assessment utilizing a multi-contrast brightfield imaging strategy.

一种基于颜色的肿瘤分割方法，利用多对比度明场成像策略进行临床离体乳腺组织评估。

• 发表时间: 2024-05
• 作者: Wang, Roujia;Ekem, Lillian;Gallagher, Jennifer;Factor, Rachel E;Hall, Allison;Ramanujam, Nimmi
• 通讯作者: Ramanujam, Nimmi

Adaptive Design of Fluorescence Imaging Systems for Custom Resolution, Fields of View, and Geometries.

针对自定义分辨率、视场和几何形状的荧光成像系统的自适应设计。

• 发表时间: 2023
• 作者: Wang, Roujia;Deutsch, Riley J;Sunassee, Enakshi D;Crouch, Brian T;Ramanujam, Nirmala
• 通讯作者: Ramanujam, Nirmala

In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence.

体内代谢成像可识别 Her2 /Neu 乳腺癌残留病灶和复发的临床前模型中的脂质脆弱性。

• 发表时间: 2022-09-26
• 影响因子: 5.9
• 作者: Madonna, Megan C;Duer, Joy E;McKinney, Brock J;Sunassee, Enakshi D;Crouch, Brian T;Ilkayeva, Olga;Hirschey, Matthew D;Alvarez, James V;Ramanujam, Nirmala
• 通讯作者: Ramanujam, Nirmala