Imaging MALDI MS produces molecular images of peptides, proteins, lipids and metabolites present in intact tissue sections.  It employs desorption of molecules by direct laser irradiation to map the location of specific molecules from fresh frozen and formalin fixed tissue sections without the need of target specific reagents such as antibodies. Molecular maps can be directly correlated to known histological regions within the tissue. Images are produced in specific m/z (mass-to-charge) values, or ranges of values, typically covering the MW range 1000-100,000.  Individual m/z values derived from each pixel can then be assembled to produce selected molecular images.  Similarly, we have developed a protocol termed histology-directed molecular analysis whereby only selected areas of cells in the tissue are of interest are ablated and analyzed based on studies performed by microscopy and other histology protocols.  Both fresh frozen and formalin fixed tissues can be analyzed.We have employed Imaging MS in studies of a variety of diseases, including kidney disease, cancers, and neurodegenerative disease, comparing proteins differentially expressed in diseased tissue with compared to normal tissue and comparing different stages of disease. Molecular signatures are obtained that differentiate these tissues, typically consisting of 10-20 or more different proteins. These diagnostic proteins are then identified using classical proteomics methods.  Imaging MS has been applied to drug targeting and metabolic studies following drug administration.             This presentation will focus on recent technological advances both in sample preparation and instrumental performance to achieve images at high spatial resolution (<10 microns) and at high speeds so that a typical sample tissue (e.g., a whole mouse brain section) can be imaged in less than 10 min.  Some selected examples will include studies of diabetic nephropathy, tumor bearing tissues and normal developmental processes.  Other aspects of the technology, such as 3-D imaging, will also be discussed.

Molecular imaging of tissue sections by mass spectrometry: Looking beyond the microscope

244th National Meeting (2012)

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