Cellular resolution in clinical MALDI mass spectrometry imaging: the latest advancements and current challenges.

Cellular resolution in clinical MALDI mass spectrometry imaging: the latest advancements and current challenges.
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DOI:
10.1515/cclm-2019-0858
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发表时间:
2020-06-25
影响因子:
6.8
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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质谱(MS)是代谢组学、蛋白质组学和脂质组学的主力。质谱成像(MSI),其延伸到组织的空间分辨分析,是一个强大的工具,可视化组织的组织背景下的分子信息。本文综述了MSI的最新进展,并强调了当前在临床标本细胞水平上实现分子成像的挑战。我们专注于基质辅助激光解吸/电离(MALDI)-MSI。我们讨论了每个分析步骤的当前状态和剩余的挑战,以达到所需的细胞成像水平。目前,分析物离域和降解,基质晶体尺寸,激光聚焦限制和检测器灵敏度是限制空间分辨率的因素。正在开发新的样品制备设备和激光光学系统,以突破这些限制。此外,我们回顾了细胞MSI数据和图像的处理,以及根据现有算法和数据库对这些数据进行系统整合。我们讨论了数据分析管道中的障碍,并展示了如何使用其他领域的技术来克服这些障碍。最后,我们总结了需要采取的治疗和社区努力,以使所获得的信息能够情境化。
Mass spectrometry (MS) is the workhorse of metabolomics, proteomics and lipidomics. Mass spectrometry imaging (MSI), its extension to spatially resolved analysis of tissues, is a powerful tool for visualizing molecular information within the histological context of tissue. This review summarizes recent developments in MSI and highlights current challenges that remain to achieve molecular imaging at the cellular level of clinical specimens. We focus on matrix-assisted laser desorption/ionization (MALDI)-MSI. We discuss the current status of each of the analysis steps and remaining challenges to reach the desired level of cellular imaging. Currently, analyte delocalization and degradation, matrix crystal size, laser focus restrictions and detector sensitivity are factors that are limiting spatial resolution. New sample preparation devices and laser optic systems are being developed to push the boundaries of these limitations. Furthermore, we review the processing of cellular MSI data and images, and the systematic integration of these data in the light of available algorithms and databases. We discuss roadblocks in the data analysis pipeline and show how technology from other fields can be used to overcome these. Finally, we conclude with curative and community efforts that are needed to enable contextualization of the information obtained.