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.

Keywords: chemical imaging; imaging mass spectrometry; multimodal analysis; tissue analysis.

Figure 1.

Selected developments within the IMS community. Image of a Vero B cell culture at 1 μm spatial resolution acquired with transition mode MALDI-2 IMS developed by the Dreiswerd lab (A). Panel A is adapted with permission from ref . Copyright 2019 Nature Publishing. SIMS image of a coculture of different Pseudomonas aeruginosa strains visualized with different signaling small molecules (B). Panel B is adapted with permission from ref . Copyright 2019 SPIE. Digital Library. Lipid images both positive and negative mode of the mouse uterine tissue using nanoDESI at 10 μm spatial resolution (C). Panel C is adapted with permission from ref . Copyright 2019 Nature Publishing.

Figure 2.

LESA and cIM analysis of a complex murine kidney protein extract. More proteins are detected after each additional cycle of cIM (A). IM heat map generated from a single cycle of cIM (B), where extracted mass spectra from different trend lines contain different protein signatures (C–E). This figure was adapted with permission from ref . Copyright 2020 American Chemical Society.

Figure 3.

Images of a TEM grid (A–C) and NaCl salt (D–F) crystal generated from the SIMS helium microscope. The SIMS (B, C, E, and F) images are close to the resolution of the microscopy (A and D), demonstrating the power of this technique. This figure was adapted with permission from ref . Copyright 2019 Science Direct.

Figure 4.

MALDI IMS lipid profiles obtained after FT-IR generated segmentation. Murine brain is differentially segmented based on absorbance of 2922 cm⁻¹ based on disease (A) and control mice (B). Using this segmentation, lipid profiles can be generated for different masks for chemical differentiation (C and D). This figure was adapted with permission from ref . Copyright 2018 Nature Publishing.