Label-Free Cell-Resolved Metabolomics for Tumor Microscopy

用于肿瘤显微镜检查的无标记细胞解析代谢组学

基本信息

批准号：
10359777
负责人：
Marcus T Cicerone
金额：
$ 13.83万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-13 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10359777
关键词：
Address Biological Biology Biopsy Cells Clinical Complex Diagnosis Diagnostic Disease Disease stratification Environment Equilibrium Escherichia coli Eukaryotic Cell Excision Fruit Genetic Growth Heterogeneity Human Image Immune In Situ Label Lesion Lipids Malignant Neoplasms Maps Mass Spectrum Analysis Measures Metabolic Metabolism Methods Microscope Microscopic Microscopy Modeling Modification Molecular Molecular Profiling Mus Muscle Fibers Outcome Patient-Focused Outcomes Phase Phenotype Play Prognosis Prokaryotic Cells Prostatic Neoplasms Raman Spectrum Analysis Research Research Personnel Resolution Role Sampling Series Signal Transduction Solid Neoplasm Solvents Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Speed Techniques Testing Theoretical model Therapeutic Time Tissue imaging Tissues Tumor-infiltrating immune cells Visualization software Work Xenograft procedure anticancer research aqueous base cancer recurrence clinical application data acquisition detection limit high dimensionality imaging approach imaging modality immune function instrument metabolic imaging metabolomics microscopic imaging multidimensional data novel diagnostics novel therapeutics prognostic programs routine imaging small molecule spectrograph submicron therapeutic target tissue mapping tissue/cell culture tool tumor tumor heterogeneity vibration

项目摘要

Summary It is widely held that energy creation and use strategies employed by tumors may provide important diagnostic and therapeutic opportunities. However, tools to directly and microscopically visualize these strategies do not yet exist because most of the metabolites cannot be labeled for microscopy. This project uses recently developed a coherent Raman imaging method that can rapidly obtain molecular vibration signatures of these unlabeled metabolites, potentially making them visible. If the project is successful, it will yeild a microscope that will allow cancer researchers and clinicians to, for the ﬁrst time, visualize metabolic activity in intact tumors, on a cell-by-cell basis, and should facilitate discovery of new therapies and diagnostics. Developing such an instrument presents signiﬁcant challenges. The project will approach these in our ﬁrst Aim by developing a detailed theoretical model of our imaging approach, and testing it against a simpliﬁed and well-controlled series of experimental tissue mimics. This dual model approach will allow us to discover the most effective path to realizing the necessary instrument sensitivity and reliability. In the second Aim we test the microscope in actual tissues and cell culture that is independently analyzed for content of metabolites measure by BCARS.

概括人们普遍认为，肿瘤采用的能量创造和使用策略可能会提供重要的诊断和治疗机会。但是，直接和微观可视化这些策略的工具尚未之所以存在，是因为大多数代谢物不能用于显微镜。该项目使用最近开发的连贯的拉曼成像方法，可以快速获得这些未标记的分子振动特征代谢物，有可能使它们可见。如果该项目成功，它将是一个允许的显微镜癌症研究人员和临床医生，第一次，在完整肿瘤中可视化代谢活性基础，应促进发现新疗法和诊断。开发这种工具提出了重大挑战。该项目将在我们的第一个中接近这些通过开发成像方法的详细理论模型，并根据简化和良好控制的一系列实验组织模仿。这种双重模型方法将使我们能够发现实现必要的仪器灵敏度和可靠性的最有效途径。在第二个目标中，我们测试实际组织和细胞培养中的显微镜，该显微镜对代谢物测量的含量进行独立分析由BCARS。