MALDI Imaging Mass Spectrometry (IMS) produces molecular maps 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 images of this nature are produced in specific m/z (mass-to-charge) values, or ranges of values. Each specimen gives rise to many hundreds of molecular images from a single raster of the tissue. We have developed a histology-directed approach that integrates mass spectrometry and microscopy. Mass spectra are collected from only selected areas of cells within the tissue following laser ablation and analysis.<br/>We have employed IMS in a variety of biologically and medically relevant research projects. One is the molecular mapping of molecular changes occurring in diabetes in both a mouse model and in human disease. Major molecular alterations have been recorded in advanced diabetic nephropathy involving both proteins and lipids. Others include developmental studies of embryo implantation is mouse, assessment of margins in renal cancers and other organs, and neurodegenerative disease. Molecular signatures have been identified that are differentially expressed in diseased tissue and in differentiating different stages of disease. These signatures typically consist of 10-20 or more different proteins and peptides, each identified using classical proteomics methods. One application described is the differentiation of benign skin lesions from melanomas. Our PIMS (Pathology Interface for Mass Spectrometry) will be demonstrated. Imaging MS has been applied to drug targeting and metabolic studies both in specific organs and intact whole animal sections following drug administration.  I will also describe recent technological advances both in sample preparation and instrumental performance to achieve images at high spatial resolution (1-10 microns) and at high speeds so typical sample tissues once prepared can be imaged in just a few minutes. Applications will include the use of MS/MS, ultra-high mass resolution, ion mobility, and ion accumulation devices for IMS. Finally, new biocomputational approaches will be discussed for high data dimensionality of Imaging MS and our implementation of ‘image fusion’ in terms of predictive integration of MS images with microscopy and other imaging modalities.

Imaging mass spectrometry: Molecular microscopy for biology and medicine

251st National Meeting (2016)

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