Multimodal Mass Spectrometry Imaging in Atlas Building: A Review

In the era of precision medicine, scientists are creating atlases of the human body to map cells at the molecular level, providing insight into what fundamentally makes each cell different. In these atlas efforts, multimodal imaging techniques that include mass spectrometry imaging (MSI) have revolutionized the way biomolecules, such as lipids, peptides, proteins, and small metabolites, are visualized in the native spatial context of biological tissue. As such, MSI has become a fundamental arm of major cell atlasing efforts, as it can analyze the spatial distribution of hundreds of molecules in diverse sample types. These rich molecular data are then correlated with orthogonal assays, including histologic staining, proteomics, and transcriptomics, to analyze molecular classes that are not traditionally detected by MSI. Additional computational methods enable further examination of the correlations between biomolecular classes and creation of visualizations that serve as a powerful resource for researchers and clinicians trying to understand human health and disease. In this review, we examine modern multimodal imaging methods and how they contribute to precision medicine and the understanding of fundamental disease mechanisms.