Richard M. Caprioli, Ph.D.
Vanderbilt Mass Spectrometry Research Center
Imaging Mass Spectrometry: Looking Beyond the Microscope
The spatial and temporal aspects of molecular processes in cells and tissues play an enormous part in the biology that defines living systems both in health and disease. Profiling and Imaging MALDI MS (matrix assisted laser desorption ionization mass spectrometry) provides an effective means to measure and assess these dimensions on a molecular basis, including peptides, proteins, lipids, metabolite as well as others. The technology is extraordinarily high throughput with high molecular specificity and is an excellent discovery tool. It provides the capability of mapping the location of specific molecules directly from fresh frozen and formalin fixed tissue sections.
For example, utilization of this technology provides spatial information across a tissue section for a target protein expression or for a signature of multiple proteins and can be used to correlate changes in expression levels with specific disease states or drug response. Molecular patterns can be directly correlated to known histological regions within the tissue, a technique termed histology directed molecular profiling. In the imaging mode, high density laser ablation of an ordered array of spots over the entire tissue gives rise to a 2-dimensional ion density map (or image) with 20-40 µm lateral resolution in which location and relative abundance of a given analyte is displayed. From the analysis of a single section, images at virtually any molecular weight may be obtained. Both fresh frozen and formalin fixed tissues can be analyzed. The ease and multiplex nature of the technology for monitoring molecular markers capable of being monitored will provide a new platform for molecular pathology for enhanced diagnosis, prognosis and evaluation of therapy, assessed at the molecular level for individual patients
This presentation will discuss applications of this technology, including examples of discovery of protein signatures in human tumors, characterizing protein differences between tumor grades, and for the creation of 3-D protein images. MALDI ToF MS, MS/MS, ion mobility MS and FTICR MS for profiling and imaging of tissues will be discussed. The technology has also been applied to drug metabolism and efficacy in several animal model systems.