Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.
Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.
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DOI：
10.1097/hp.0b013e3182a4ec2f
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发表时间：
2014-01
期刊：
影响因子：
2.2
通讯作者：
Ernst RK
中科院分区：
文献类型：
--
作者：
Scott AJ;Jones JW;Orschell CM;MacVittie TJ;Kane MA;Ernst RK
鉴定独特的生物标志物是确定辐射引起的组织损伤特征的一个组成部分。生物标志物的发现是一项具有挑战性和复杂性的奋进，需要复杂的实验设计和可访问的技术。国家过敏和传染病研究所（NIAID）赞助的联盟内的资源，针对放射性威胁的医学对策（MCART），允许利用强大的动物模型与新的分子成像技术。一种这样的成像技术，MALDI（基质辅助激光解吸电离）质谱成像（MSI），允许直接空间可视化的脂质，蛋白质，小分子和药物/药物代谢物-或生物标志物-在一个公正的方式。MALDI-MSI直接从完整组织切片中跨x，y网格的离散位置获取质谱，然后将其绘制成由离子质量和强度组成的空间分布图。可以绘制独特的质量信号以生成反映病理学和分子事件的生物标志物的空间图。MALDI-MSI可以解决的关键未回答的问题包括识别辐射损伤的生物标志物，这些生物标志物反映了随着时间的推移对辐射剂量的反应和治疗干预的疗效。MALDI-MSI中的技术还使得能够在不同的动物模型中整合生物标志物鉴定。对来自不同小鼠组织（肺和回肠）的早期亚致死剂量辐照组织损伤样本的分析显示，膜磷脂特征与这些独特组织的组织学特征相关。本文将讨论MALDI-MSI在更大的生物标志物发现管道中的应用。
Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites—or biomarkers—in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.