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: 8233645
• 负责人: RICHARD M CAPRIOLI
• 金额: $ 45.11万
• 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/8233645
• 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; tumor growth

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. PUBLIC HEALTH RELEVANCE: 3-D Imaging Mass Spectrometry will provide an exciting new approach for mapping molecular constituents in tissue volumes in an unbiased manner (i.e., without the need for antibodies). The information obtained will allow chemical annotation, improved interpretation and validation to classical imaging technologies, i.e., MRI, PET and microscopy. A major innovative aspect of the work is that it can provide data relevant to the anatomy of the whole organ or entire animal with high spatial fidelity and unmatched molecular specificity.

描述（由申请人提供）：拟议研究的目标是开发高分辨率 3-D 成像质谱 (IMS) 技术，使其达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 矩阵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、及时的方式提供多个连续切片的数据。计划开发协议，允许在组织体积中以 3D 方式跟踪肽、蛋白质、脂质和药物以及其他小分子。此外，还计划完成重要的生物计算工作，以处理数据维数和尺寸减小、单个 2D 实验中图像相对定量的离子强度标准化和跨组织体积连续切片的 3D 重建、以解剖保真度配准切片以及在实际时域中生成单个分子的 3D 图像。 这项技术将解决几个重要的生物学问题； 1) 评估小鼠大脑纹状体中纹状体的 3-D 分子分布和边界，以及与帕金森病、亨廷顿病和强迫症等神经精神疾病有关的亚结构，2) 小鼠模型视神经中肿瘤和微环境中神经胶质瘤生长、进展和维持中分子事件的 3-D 绘图 与大脑图谱中现有的 3-D 显微图像相链接，3) 3-D IMS 数据与其他成像方式的共同配准；研究用于 PET 成像的造影剂的处置和代谢、通过 MRI 阐明扩散加权成像中的分子方面，以及通过 IMS 获得的分子事件与 MR 弛豫数据的共同配准/相关性。这项工作将汇集几种强大的成像模式，并通过每种模式的独特属性，在理解整个组织动力学方面获得组合优势。其目标之一是，计划将显微镜和 IHC 测量、MRI 和 IMS 结合起来，作为单个 3D 体积的一部分，可以使用标准互联网工具轻松查询。 公共健康相关性：3D 成像质谱仪将提供一种令人兴奋的新方法，以公正的方式（即不需要抗体）绘制组织体积中的分子成分。获得的信息将允许对经典成像技术（即 MRI、PET 和显微镜）进行化学注释、改进解释和验证。这项工作的一个主要创新方面是它可以提供与整个器官或整个动物的解剖学相关的数据，具有高空间保真度和无与伦比的分子特异性。