MALDI imaging – a new tool for mapping multiple sclerosis brain lesions

Objective: Remyelination of multiple sclerosis brain lesions is an important mechanism to prevent chronic disability. However, the exact mechanism remains elusive. Recently, protein analysis using Mass Spectrometry Imaging has become feasible, which visualises protein and peptide spatial distributions. Methods: We employed Matrix Assisted Laser Desorption Ionisation Mass Spectrometry (MALDI-MSI) to identify peptides and proteins expressed in normal-appearing white matter, grey matter and MS brain lesions with different extents of remyelination. The results were compared with serial slides stained by standard histochemistry and immunohistochemistry. Results: Statistical analyses of mass spectra obtained from unsupervised hierarchical clustering and principle component analysis, generated molecular images which were used to define regions that agreed with those obtained from histological analysis. Remyelination extent correlated with molecular weight of the compounds. A supervised clustered mass spectrometry dataset led to the discovery of a cortical lesion that was not visible by routine histology, but confirmed by subsequent immunostaining. Interpretation: MALDI-MSI has the ability to distinguish lesions with different extents of remyelination, to detect cortical lesions that were not visible on routine histopathology stains and to define structurally distinct sub-regions with similar expression profiles and localisations of potentially disease-related proteins and peptides.