High spatial resolution mass spectrometry imaging for spatial metabolomics: Advances, challenges, and future perspectives

Spatial metabolomics is an emerging field of omics research that has enabled localizing small molecules in tissues and cells. Mass spectrometry imaging (MSI) technologies allow visualizing the spatial distribution of chemicals directly from biological samples without labeling and are becoming increasingly vocal for biological applications. Spatial metabolomics and its enabling technology, MSI, generate enormous visualization information that has extended the metabolomics information from point to plane and further motivates the development of MSI technology toward high spatial resolution and its application prospect in spatial metabolomics. Here, we highlight the latest advances in high spatial resolution MSI techniques for cellular and subcellular level imaging of metabolites and summarize the recent applications of spatial metabolomics based on high spatial resolution MSI for identification, quantitation, localization, and metabolic pathways of endogenous and exogenous compounds in tissues and single cells. We also prospect high spatial resolution MSI challenges based on the requirement for spatial metabolomics. This review is intended to provide readers with the latest progress of high spatial resolution MSI techniques and applications in spatial metabolomics, and discusses the potential challenges.