Label-Free Cell-Resolved Metabolomics for Tumor Microscopy

摘要 人们普遍认为，肿瘤所采用的能量创造和利用策略可能提供重要的诊断 和治疗机会。然而，直接和微观地可视化这些战略的工具还没有 之所以存在，是因为大多数代谢物不能在显微镜下标记。这个项目使用了最近开发的 一种可以快速获得这些未标记分子振动特征的相干拉曼成像方法 代谢物，潜在地使它们可见。如果这个项目成功，它将生产出一种显微镜，它将使 癌症研究人员和临床医生首次在fi上逐个细胞地可视化完整肿瘤中的代谢活动 并应有助于发现新的治疗方法和诊断方法。 开发这样一种仪器面临着巨大的挑战。该项目将在我们的fiFirst中处理这些问题 目的为我们的成像方法开发一个详细的理论模型，并在SimplifiED和 控制良好的一系列实验组织模拟。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 显微镜在实际组织和细胞培养中独立分析代谢物含量的测量 由BCARS提供。

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.