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

金属和金属蛋白在大脑和肝脏的代谢和含金属沉积物的形成中起着关键作用。在各种疾病中，金属和金属蛋白的分析对于理解潜在的细胞和系统机制至关重要。质谱成像（MSI）结合其他成像方式是研究金属和相关生物分子的区域和细胞分布的一种新选择。因此，成像是一个必要的步骤，特别是在大脑中，因为它的区域组织不均匀。基于我们在空间分辨率在200 ~ 10 μm之间的LA-ICP-MSI元素成像方面的经验，我们建议：1)进一步发展LMD-ICP-MSI以更高的空间分辨率（10 ~ 0.3 μm；细胞水平）对金属进行成像；2)建立LA/LMD-ICP-MSI元素成像与MALDI-MSI分子成像相结合的方法；3)将这些技术应用于正常和病变的脑和肝脏；4)研究金属和金属蛋白在正常和病理人体组织中的分布，以及在神经退行性疾病和肝脏疾病的敲除动物模型和缺乏明确（金属）蛋白的动物模型中的分布；5)将这些方法转移到其他脑部疾病（如癫痫）和其他器官的分析。总之，我们将把现有的BrainMet平台发展为高质量分辨率和高空间分辨率的MSI技术，使金属和金属蛋白的分析从单细胞到系统水平。

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.