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High-resolution volumetric imaging of metabolic activity in tissues and its application to tumor metabolism

组织代谢活动的高分辨率体积成像及其在肿瘤代谢中的应用

基本信息

批准号：
10376225
负责人：
Wei Min
金额：
$ 37.06万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
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：
2020-05-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376225
关键词：
3-Dimensional Address Aging Animals Beds Biological Process Cells Characteristics Chemicals Cluster Analysis Colonic Neoplasms Computer Analysis Coupled Data Detection Deuterium Oxide Development Disease Disease Progression Exhibits Fluorescence Fluorescence Microscopy Fluorescent Probes Generations Genetic Glioblastoma Goals Health Heterogeneity Image Imaging Techniques In Situ Individual Knowledge Label Lasers Life Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Malignant Neoplasms Maps Mass Spectrum Analysis Metabolic Metabolism Methods Microscope Microscopy Molecular Monitor Mus Nature Neurodegenerative Disorders Optics Organ Penetration Physiology Positron-Emission Tomography Protocols documentation Recipe Resolution Sampling Specificity Surface Tail Techniques Technology Testing Thick Time Tissues Treatment Protocols Tumor Tissue Warburg Effect animal tissue cancer imaging cancer therapy cell type imaging modality in vivo instrumentation interdisciplinary approach macromolecule metabolic imaging millimeter next generation novel rational design screening technology development treatment strategy tumor tumor heterogeneity tumor metabolism tumor xenograft two-photon vibration

项目摘要

Project Summary Genetics and metabolism are two defining characteristics of life. Understanding metabolism in animals is critical to unraveling the mechanistic basis of many biological processes in health and diseases, such as development, aging and cancer. For normal physiology, it is the synthesis, transformation and degradation of biomolecules (i.e., metabolic activity) that carry out the genetic blueprint of animals. For diseases, metabolic reprogramming is a hallmark for cancer (such as the Warburg effect). However, popular imaging techniques such as magnetic resonance spectroscopy, positron emission tomography, imaging mass spectroscopy and fluorescence microscopy all exhibit inherent limitations towards noninvasive high-resolution metabolic imaging. Therefore, there is no current metabolic imaging technique that can offer the desired combination of in situ probing, single-cell resolution, and volumetric imaging of three-dimensional (3D) tissues. Such technology would contribute to mechanistic understanding of normal physiology and disease progression such as tumor. The goal of this project is to develop a novel optical technology for in situ high-resolution volumetric imaging of metabolic activity in animal tissues, capturing metabolic status of every cell throughout 3D tissues. We have laid out a multi-disciplinary approach including exploration of in vivo labeling probe, novel sample treatment protocol, new microscope instrumentation construction, and multivariate computational analysis. Aim 1 is about developing heavy water (D2O) as a universal probe to be coupled with the emerging stimulated Raman scattering (SRS) microscopy, to monitor metabolic activities of tissues in a multiplex manner. Our preliminary data have demonstrated the feasibility. Advanced computational analysis and hyperspectral SRS instrumentation will be developed to achieve comprehensive metabolic profiling. Aim 2 aims to establish a volumetric imaging method to generate 3D metabolic activity maps deep into tissues. We propose to develop Raman-tailored clearing recipe that will open up volumetric SRS imaging of thick tissues and whole organs. Our preliminary data have achieved more than 10 times SRS imaging depth extension than previously possible. Aim 3 will integrate and tailor the technical development from Aim 1 and Aim 2 for imaging metabolic heterogeneity of tumor tissue. We propose to construct correlative fluorescence and SRS microscope and employ multivariate computational analysis. These development will be integrated to obtain cell-type-specific metabolic activity profiling (including different types of newly-synthesized molecules) within 3D tumor tissues, facilitating understanding of the causes, progression and refined treatment strategies of cancer. 1

项目总结