Focus on MALDI imaging

Abstract

Matrix-assisted laser desorption/ionization (MALDI) emerged in the late 1980s concomitantly with electrospray ionization and contributed substantially to the promotion of mass spectrometry as an invaluable tool for analysis of biological macromolecules. Because MALDI is based on the production of ions from solid-phase samples deposited onto a conducting surface, some researchers attempted to analyse directly biological materials without any preliminary extraction step. MALDI analysis of bacterial cultures as early as the mid-1990s illustrates this approach, the objective of these studies being to characterize and identify microorganisms on the basis of a set of characteristic peaks present in their mass spectra. Identification of bacteria by MALDI mass spectrometry is now a routine method for clinical use. The ability of MALDI mass spectrometry to obtain spectra on well-defined surfaces with a focus of approximately 50–100 μm should also enable linking of the histological characteristics of biological tissue with local molecular composition. The driving idea was that tissue heterogeneity could be correlated with a difference in the mass spectral peak patterns. MALDI “profiling” of tissue sections was then proposed by the Todd and Caprioli groups at the end of the 1990s to differentiate, on a molecular basis, healthy or pathological areas present within the same tissue section. Soon after, the Caprioli team proposed a method for systematic profiling in which mass spectra were recorded at regularly spaced points on a biological surface, leading to a global vision of the molecular composition of the sample. By translating the relative intensity values of the ion peaks into a colour code, differences in local abundances in the x–y plane of the sample were revealed as contrast changes in the generated images. Immediately, MALDI mass spectrometry imaging (MALDI–MSI) seemed to be a unique method to record simultaneously as many images as ion peaks present on the mass spectra and without any a priori information about the nature of the detected molecules. It is therefore logical that MALDI imaging has initially been developed for research on biomarkers of pathologies, in a context in which the “omics” methods, in particular proteomics, have experienced explosive growth. If MALDI imaging was originally devoted to protein analysis only, this approach quickly met its limits in this area. Measuring the protein ions at low or moderate mass resolution is, indeed, not sufficient for their straightforward identification. In this area, MALDI imaging seemed more a complementary step to conventional proteomic analysis rather than an alternative method. In this way, MALDI imaging can provide precious indications of in situ protein-expression changes, making this technique attractive as a future diagnostic tool in biomedical research (Hanrieder et al., in this special issue). Recent years have seen a growing number of methodological developments and applications of MALDI imaging in the field of “small molecules”. For such compounds, accurate mass measurements, associated or not with tandemmass spectrometry (MS–MS), are often sufficient for assignment of the structures of the detected ions. Illustrating this evolution, the analysis of lipids is now a major field of application of MALDI imaging (Fernandez et al., Garrett et al., and Hart et al., in this special issue). Published in the special issue MALDI Imaging with Guest Editor Olivier Laprevote