Advanced Mass Spectrometry Imaging of Metals and Biomolecules in Brain and Liver

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Metals and metalloproteins play a key-role in metabolism and formation of metal-containing deposits in brain and liver. In various diseases, analysis of metals and metalloproteins is essential for understanding the underlying cellular and systemic mechanisms. Mass spectrometry imaging (MSI) combined with other imaging modalities is a novel option to study the regional and cellular distribution of metals and related biomolecules. Thereby, imaging is a necessary step, particularly in the brain because of its inhomogeneous regional organization. Based on our experience in elemental imaging using LA-ICP-MSI with a spatial resolution between 200 to ∼10 μm, we propose: 1) to further develop LMD-ICP-MSI to imaging of metals at higher spatial resolution (10 to 0.3 μm; cellular level); 2) to develop a method combining elemental imaging by LA/LMD-ICP-MSI with molecular imaging by MALDI-MSI; 3) to apply these techniques to the normal and diseased brain and liver; 4) to study metals and metalloproteins distributions in normal and pathological human tissue as well as in knockout animal models of neurodegenerative and hepatic disorders and those lacking defined (metallo)proteins; 5) to transfer these methods to analyses of other brain disorders, e.g. epilepsy, and to other organs. In summary, we will develop the existing BrainMet platform to high mass resolution and high spatial resolution MSI techniques enabling the analysis of metals and metalloproteins from the single cell to the systemic level.