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：
10551256
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/10551256
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 Tissues Treatment Protocols Tumor Tissue Visualization Warburg Effect animal tissue cancer imaging cancer therapy cell type imaging modality in vivo instrumentation interdisciplinary approach invention macromolecule metabolic imaging millimeter next generation novel rational design screening technology development treatment strategy tumor tumor heterogeneity tumor metabolism tumor xenograft two-photon

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

项目概要遗传学和新陈代谢是生命的两个决定性特征。了解动物的新陈代谢是对于揭示健康和疾病中许多生物过程的机制基础至关重要，例如发育、衰老和癌症。对于正常生理来说，它是合成、转化和降解的过程。执行动物遗传蓝图的生物分子（即代谢活动）。对于疾病、代谢重编程是癌症的一个标志（例如瓦尔堡效应）。然而，流行的成像技术例如磁共振波谱、正电子发射断层扫描、成像质谱和荧光显微镜对于无创高分辨率代谢成像都表现出固有的局限性。因此，目前没有代谢成像技术可以提供所需的组合原位探测、单细胞分辨率和三维 (3D) 组织的体积成像。这样的技术将有助于对正常生理学和疾病进展的机械理解，例如作为肿瘤。该项目的目标是开发一种用于原位高分辨率体积测量的新型光学技术对动物组织中的代谢活动进行成像，捕获整个 3D 组织中每个细胞的代谢状态。我们制定了多学科方法，包括探索体内标记探针、新样品治疗方案、新型显微镜仪器构造和多变量计算分析。目标 1 是开发重水 (D2O) 作为通用探针，与新兴的受激拉曼散射 (SRS) 显微镜，以多重方式监测组织的代谢活动。我们的初步数据证明了可行性。先进的计算分析和高光谱 SRS 将开发仪器以实现全面的代谢分析。目标 2 旨在建立一个体积成像方法可生成组织深处的 3D 代谢活动图。我们建议开发拉曼定制的透明配方将开启厚组织和整个器官的体积 SRS 成像。我们的初步数据已经实现了比以前超过10倍的SRS成像深度扩展。 Aim 3 将整合和定制 Aim 1 和 Aim 2 的技术开发，用于成像代谢肿瘤组织的异质性。我们建议建造相关荧光和SRS显微镜采用多元计算分析。这些开发将被整合以获得细胞类型特异性 3D 肿瘤组织内的代谢活动分析（包括不同类型的新合成分子），促进对癌症的病因、进展和精细治疗策略的了解。 1

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Raman Imaging Reveals Insights into Membrane Phase Biophysics in Cells.

拉曼成像揭示了细胞膜相生物物理学的见解。

DOI：
10.1021/acs.jpcb.3c03125
发表时间：
2023-07-11
期刊：
The journal of physical chemistry. B
影响因子：
0
作者：
Yihui Shen;Lu Wei;Wei Min
通讯作者：
Wei Min

Single-particle imaging of nanomedicine entering the brain.

DOI：
10.1073/pnas.2309811121
发表时间：
2024-01-22
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Mian Wei;Naixin Qian;Xin Gao;Xiaoqi Lang;Donghui Song;Wei Min
通讯作者：
Wei Min

Raman scattering and vacuum fluctuation: An Einstein-coefficient-like equation for Raman cross sections.

拉曼散射和真空涨落：拉曼截面的类爱因斯坦系数方程。