Spatial Analysis of Molecules in Tissue using MALDI-MS

使用 MALDI-MS 对组织中的分子进行空间分析

• 批准号: 8588333
• 负责人: RICHARD M CAPRIOLI
• 金额: $ 42.96万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588333
• 关键词: 3-Dimensional; Address; Affect; Anatomy; Animals; Antibodies; Atlases; Autologous Expanded Mesenchymal Stem Cells; Autoradiography; Biological; Brain; Chemicals; Colonic Neoplasms; Contrast Media; Corpus striatum structure; Data; Data Set; Development; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Event; Face; Generations; Glioma; Gliomagenesis; Goals; Growth; Histology; Human; Huntington Disease; Hypoxia; Image; Imaging technology; Individual; Internet; Ions; Lasers; Lipids; Magnetic Resonance Imaging; Maintenance; Maps; Mass Spectrum Analysis; Measurement; Metabolism; Microscopy; Molecular; Mus; Obsessive-Compulsive Disorder; Optic Chiasm; Optic Nerve; Optic Nerve Glioma; Organ; Parkinsonian Disorders; Pattern; Peptides; Pharmaceutical Preparations; Positron-Emission Tomography; Preparation; Proteins; Protocols documentation; Relative (related person); Relaxation; Resolution; Sampling; Spatial Distribution; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; Structure; Technology; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Validation; Variant; Work; combinatorial; copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); imaging modality; imaging probe; improved; innovation; molecular imaging; mouse model; neuropsychiatry; novel strategies; protein distribution; reconstruction; research study; small molecule; striosome; subcutaneous; tissue preparation; tool; tumor growth; tumor microenvironment

DESCRIPTION (provided by applicant): The goal of the proposed studies is to develop high resolution 3-D Imaging Mass Spectrometry (IMS) technology to a level that it is capable of delivering high resolution images in a practical time frame. High spatial resolution IMS (~10 um) will be employed with tissue preparation protocols that provide 1 um matrix crystal sizes and high speed lasers (.3 kHz) to provide data on multiple serial sections in a efficacious and timely manner. It is planned to develop the protocols that would allow peptides, proteins, lipids and drugs and other small molecules to be tracked in a 3-D manner in a tissue volume. In addition, work is planned to accomplish the significant biocomputational effort needed to deal with data dimensionality and size reduction, normalization of ion intensities for the relative quantitation of images both within a single 2-D experiment and across serial sections of a tissue volume for 3-D reconstruction, registration of the sections with anatomic fidelity, and generation of a 3-D images of individual molecules in a practical time domain. Several important biological problems will be addressed with this technology; 1) assessment of the 3-D molecular distributions and boundaries of striosomes in the striatum of the mouse brain, substructures implicated in neuropsychiatric disorders such as Parkinsonism, Huntington's Disease, and obsessive-compulsive disorder, 2) 3-D mapping of molecular events in glioma growth, progression, and maintenance, both in the tumor and microenvironment, in the optic nerve of a mouse model with linkage to existing 3-D microscopy images in the brain atlas, 3) Co-registration of 3-D IMS data with other imaging modalities; studies of the disposition and metabolism of contrast agents used for PET imaging, the elucidation of molecular aspects in diffusion weighted imaging by MRI, and the co-registration/correlation of molecular events obtained by IMS with MR relaxation data. This work will bring together several powerful imaging modalities and, through the unique attributes of each, gain a combinatorial advantage in understanding whole tissue dynamics. In one aim, it is planned to combine microscopy and IHC measurements, MRI and IMS as part of a single 3-D volume that is easily interrogated using standard internet tools.

描述（由申请人提供）：拟定研究的目标是将高分辨率3-D成像质谱（IMS）技术开发到能够在实际时间范围内提供高分辨率图像的水平。高空间分辨率IMS（~10 um）将与提供1 um基质晶体尺寸和高速激光（.3 kHz）的组织制备方案一起使用，以有效和及时的方式提供多个连续切片的数据。计划开发的协议将允许肽，蛋白质，脂质和药物和其他小分子以三维方式在组织体积中进行跟踪。此外，计划开展工作，以完成处理数据维数和尺寸减小所需的重要生物计算工作，在单个2-D实验内和跨组织体积的连续切片进行3-D重建的图像相对定量的离子强度归一化，具有解剖保真度的切片的配准，以及在实际时域中产生单个分子的3-D图像。 几个重要的生物学问题将通过这项技术得到解决; 1）评估小鼠脑纹状体中纹状体的3-D分子分布和边界，神经精神障碍如帕金森氏症、亨廷顿病和强迫症中涉及的亚结构，2）肿瘤和微环境中神经胶质瘤生长、进展和维持中的分子事件的3-D绘图，在小鼠模型的视神经中，与脑图谱中现有的3-D显微镜图像相关联，3）3-D IMS数据与其他成像模态的共配准;用于PET成像的造影剂的处置和代谢的研究，通过MRI对扩散加权成像中的分子方面的阐明，以及通过IMS获得的分子事件与MR弛豫数据的共配准/相关性。这项工作将汇集几个强大的成像模式，并通过每个独特的属性，获得在理解整个组织动态的组合优势。在一个目标中，计划将联合收割机显微镜和IHC测量、MRI和IMS结合起来，作为单个3-D体积的一部分，使用标准的互联网工具可以轻松地进行询问。