Multimodal Imaging Mass Spectrometry: Next Generation Molecular Mapping in Biology and Medicine

Abstract

Imaging mass spectrometry has become a mature molecular mapping technology that is used for molecular discovery in many medical and biological systems. While powerful by itself, imaging mass spectrometry can be complemented by the addition of other orthogonal, chemically informative imaging technologies to maximize the information gained from a single experiment and enable deeper understanding of biological processes. Within this review, we describe MALDI, SIMS, and DESI imaging mass spectrometric technologies and how these have been integrated with other analytical modalities such as microscopy, transcriptomics, spectroscopy, and electrochemistry in a field termed multimodal imaging. We explore the future of this field and discuss forthcoming developments that will bring new insights to help unravel the molecular complexities of biological systems, from single cells to functional tissue structures and organs.

Protocol for multimodal analysis of human kidney tissue by imaging mass spectrometry and CODEX multiplexed immunofluorescence

“…This protocol describes imaging mass spectrometry (IMS) specific sample preparation and IMS analysis on fresh frozen tissue sections for 10 μm spatial resolutions for 200 lipid species. ( Neumann et al., 2020a , Caprioli et al., 1997 , McDonnell and Heeren, 2007 ) Matrix application onto the tissue surface. Apply 6 psi of nitrogen to the sprayer nozzle and turn on the TM sprayer.…”

Viv: Multiscale Visualization of High-Resolution Multiplexed Bioimaging Data on the Web

“…Due to its modular architecture, Viv is embeddable and can be deployed to support visualization for exploration and explanation in a wide range of different settings (see Supplementary Note 3). For example, we integrated Viv into Jupyter Notebooks 13 as an ImJoy 14 plugin to enable a human-in-the-loop multimodal image registration workflow, allowing rapid iteration of registration methods and inspection of results within the same notebook environment. Viv was also integrated into an Angular-based ( https://angular.io ), ontology-driven exploration tool for human tissue datasets, further establishing its utility as a component in visual exploration tools and its compatibility with different development frameworks.…”

“…Primary data produced by multiplexed imaging methods [10][11][12][13] , however, are instead stored as multi-dimensional image stacks where each image-or channel-typically represents a chemical signal, such as a fluorophore bound to an antibody in immunofluorescence. Images derived from non-targeted methods like imaging mass spectrometry 14 (IMS) can be stored similarly with very deep stacks along the m/z dimension. These multi-dimensional stacks may contain over a hundred 16-or 32-bit grayscale images that must be pseudo-colorized for visualization, and it is desirable to view each channel separately since the specificity of the acquisition methods is high.…”

Streamlined Multimodal DESI and MALDI Mass Spectrometry Imaging on a Singular Dual-Source FT-ICR Mass Spectrometer

“…With recent breakthroughs in prognostic and diagnostic applications, these analyses still require orthogonal confirmation despite high-resolution/accurate mass (HR/AM) analysis [5]. This has created many combined imaging approaches-known in the field as multimodal or multimode imaging, providing a secondary or tertiary round of analysis of the same (or serial) section [6]. Many have identified the tandem utility of comprehensive mapping of biomolecules from MSI, with targeted assays having incorporated multiple ionization sources or MSI methods [7][8][9][10], combination of MSI with microscopy and spectroscopy [11][12][13][14][15][16], and subsequent microdissection and extraction for liquid chromatography [17,18].…”