Mass Spectrometry Imaging (MSI) Delineates Thymus-Centric Metabolism In Vivo as an Effect of Systemic Administration of Dexamethasone

Abstract

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is increasingly used in a broad range of research due to its ability to visualize the spatial distribution of metabolites in vivo. Here, we have developed a method, named thoracic Mass Spectrometry Imaging (tMSI), as a standard protocol of molecular imaging of whole-animal sectioning in various settings of mice in vivo. Further application of the strategy that involved the systemic administration of dexamethasone (DEX) in mice, enabled a dynamic shift in the energy status of multiple thoracic organs to be visualized, based on tMSI data of purine and pyrimidine metabolites. Furthermore, with the introduction of uniform manifold approximation and projection (UMAP) for tMSI data, metabolic profiles normally localized in the cortex and cortico-medullary junction (CMJ) of the thymus were drastically shifted as minor profiles into the medulla of DEX-treated thymus. As a massive apoptotic cell death in the thymic cortex was noticeable, a single molecule, which was upregulated in the cortex of the thymus, enabled us to predict ongoing immunosuppression by in vivo DEX-administration.