Matrix‐assisted laser desorption/ionisation mass spectrometry imaging of lipids in rat brain tissue with integrated unsupervised and supervised multivariant statistical analysis

Abstract

To date matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) analysis has been largely concerned with mapping the distribution of known analytes in tissues. An important step in the progression of its applications is the determination of unknown variants for metabolite and protein profiling in both clinical studies and studies of disease. Principal component analysis (PCA) is a statistical approach which can be used as a means of determining latent variables in multivariate data sets. In the work reported here, PCA, in both unsupervised and supervised modes, has been used to differentiate brain regions based on their lipid composition determined by MALDI-MSI. PCA has been shown to be useful in the determination of hidden variables between spectra taken from six regions of brain tissue. It is possible to identify ions of interest from the loadings plot which are likely to be more prominent in the different regions of the brain and thus differentiating between white and grey matter. It is also possible to distinguish between the grey Cerebellar Cortex and the Hippocampal formation, due to the grey Cerebellar Cortex having a positive PC2 and the Hippocampal formation having a negative PC2 score; this is only possible in supervised PCA with this data set because with unsupervised PCA the two regions overlap.

Anatomical Distribution of Lipids in Human Brain Cortex by Imaging Mass Spectrometry

“…Despite the potential applicability of this method and the growing number of papers published recently in the field of lipid IMS [9][10][11], some questions remain unanswered and numerous concerns have been raised. Most importantly, it is not clear whether the different intensities of lipid signals in different tissues or areas of a tissue are indeed due to real differences in lipid concentrations, or rather to changes in the environment from which the lipids are extracted during the desorption process [12,13].…”

MALDI imaging of neutral cuticular lipids in insects and plants

“…The quality of the resulting images strongly depends on the matrix deposition procedures [31][32][33][34]. MALDI imaging is mostly used for visualizing proteins or peptides [27,35,36], but recently MALDI imaging has been used with smaller molecules, e.g., drugs [37][38][39], secondary metabolites [40], or lipids [34,[41][42][43][44]. Mass spectrometry imaging has the potential to provide crucial insight into the function of cuticular lipids on surfaces of intact plants, insects, or other living organisms.…”

Lipid mapping of colonic mucosa by cluster TOF-SIMS imaging and multivariate analysis in cftr knockout mice

“…This represents a limitation in global studies where there are no particular targeted molecules. Multivariate approaches, like principal component analysis (PCA), allow distinguishing spatial structures and establishing correlations between tissue molecules (33)(34)(35). In this study, we performed a thorough analysis of mouse colonic mucosa by TOF-SIMS imaging in tissue samples from CF and wildtype (WT) mice, and we processed the data by PCA and other multivariate approaches.…”