Mass Spectrometry Imaging

Introduction:

Mass spectrometry imaging (MSI) is technique for direct profiling of peptides, proteins, lipids and small metabolites from tissue sections. In MSI, laser ionization selectively ionizes analytes in the regions of interest on the tissue section on a pixel-by-pixel basis. Detection of these ions generates a signal in proportion to the abundance of each analyte. By mapping the mass spectral signal intensity of each analyte for each tissue pixel, we can build ion images that visualize the abundance of that analyte over the tissue. MSI offers several advantages over the conventional histostaining methods that suggests it could be an invaluable complementary imaging tool in research and clinical settings. For example, MSI is a label free imaging technique that needs minimal a priori knowledge of the analyte of interest. In addition, its inherent high mass resolution distinguishes the MSI as one of the most specific targeting techniques that can provide superb imaging contrast. Lastly, quantitative techniques can be combined with MSI for absolute or relative quantification. We aim to adapt the MSI technique for imaging of glycans, a highly abundant and diverse post-translation modification of proteins that are altered in many of the human diseases including cancer, cardiovascular, infectious and neurodegenerative diseases.

The focus of our study is on:

  1. Developing an MSI-based technique for imaging of N-linked glycans, a subgroup of glycans attached to Asparagine residues on proteins, from formalin-fixed paraffin-embedded tissue sections.
  2. Developing a technique for quantitative mass spectrometry imaging of N-linked glycans based on the ratio of light and heavy isotopic standards.
  3. Studying the correlation of glycan structures with their underlying anatomies or pathologies.

Figure 1. MSI imaging of glycans in mouse brain tissue. (Click to view detailed caption)



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