Seeing Chemistry in Context: Mass Spectrometry Imaging for Biomedical Research and Multi-Omic Integration

Mass spectrometry imaging (MSI) has become a pivotal technology for exploiting the strengths of liquid chromatography-based mass spectrometry while providing spatial context. This technique has gained rapid traction in the field of biomedical research to enable scientists to interrogate difficult questions in drug discovery and disease mechanisms through enabling -omics unavailable by other spatial methodologies. In this chapter, we will discuss the fundamentals of a basic MSI experiment and a small selection of ionization methods available to be used for such studies. We will further discuss how to design an MSI experiment, providing insight into how to choose a model system and considerations for sample preparation, including embedding, fixation, and preparing sections for MALDI MSI. With this discussion, we will also touch on leveraging multi-omics experiments and how to plan accordingly. Through recent literature examples, we will further illustrate how integrating MSI with other omics layers, such as bulk analyses and spatial transcriptomics, reveals molecular changes that inform both mechanistic biology and translational research.