State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China.
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Mass Spectrom Rev. 2022 May;41(3):469-487. doi: 10.1002/mas.21674. Epub 2020 Dec 9.
Mass spectrometry imaging (MSI) has been applied for label-free three-dimensional (3D) imaging from position array across the whole organism, which provides high-dimensional quantitative data of inorganic or organic compounds that may play an important role in the regulation of cellular signaling, including metals, metabolites, lipids, drugs, peptides, and proteins. While MSI is suitable for investigation of the spatial distribution of molecules, it has a limitation with visualization and quantification of multiple molecules. 3D-MSI, however, can be applied toward exploring metabolic pathway as well as the interactions of lipid-protein, protein-protein, and metal-protein in complex systems from subcellular to the whole organism through an untargeted methodology. In this review, we highlight the methods and applications of MS-based 3D imaging to address the complexity of molecular interaction from nano- to micrometer lateral resolution, with particular focus on: (a) common and hybrid 3D-MSI techniques; (b) quantitative MSI methodology, including the methods using a stable isotope labeling internal standard (SILIS) and SILIS-free approaches with tissue extinction coefficient or virtual calibration; (c) reconstruction of the 3D organ; (d) application of 3D-MSI for biomarker screening and environmental toxicological research. 3D-MSI quantitative analysis provides accurate spatial information and quantitative variation of biomolecules, which may be valuable for the exploration of the molecular mechanism of the disease progresses and toxicological assessment of environmental pollutants in the whole organism. Additionally, we also discuss the challenges and perspectives on the future of 3D quantitative MSI.
质谱成像（MSI）已被应用于无标记的三维（3D）成像，可从整个生物体的位置阵列进行分析，提供无机或有机化合物的高维定量数据，这些化合物可能在细胞信号调节中发挥重要作用，包括金属、代谢物、脂质、药物、肽和蛋白质。虽然 MSI 适用于研究分子的空间分布，但它在可视化和量化多种分子方面存在局限性。然而，3D-MSI 可以通过非靶向方法应用于探索代谢途径，以及在复杂系统中脂质-蛋白质、蛋白质-蛋白质和金属-蛋白质的相互作用，从亚细胞到整个生物体。在这篇综述中，我们重点介绍了基于 MS 的 3D 成像方法及其应用，以解决从纳米到微米横向分辨率的分子相互作用的复杂性，特别关注：（a）常见和混合的 3D-MSI 技术；（b）定量 MSI 方法学，包括使用稳定同位素标记内标（SILIS）和无 SILIS 方法的定量方法，具有组织消光系数或虚拟校准；（c）3D 器官的重建；（d）3D-MSI 在生物标志物筛选和环境毒理学研究中的应用。3D-MSI 定量分析提供了生物分子的准确空间信息和定量变化，这对于探索疾病进展的分子机制和整个生物体中环境污染物的毒理学评估可能具有重要价值。此外，我们还讨论了 3D 定量 MSI 的未来挑战和展望。
