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Recent studies performed these last years on the proteome have demonstrated the usefulness of mass spectrometry The combination of mass spectrometry with classical biochemical methods has lead to the determination and identification of different proteins using proteomics studies in close relation with genome databases. Although such methods generally lead to the identification of novel proteins, they do not allow determining the cellular localization or regulation of peptide/proteins expression in tissues, cellular groups or single cells. New emerging technologies enable the development of alternative methodologies to address such questions so called MALDI imaging or SIMS. This is the aim of this issue of Current Pharmaceutical Design devoted of 4 reviews on Imaging by mass spectrometry and their application in neuropathologies and clinical investigations. This first article from Fournier team [1] is to highlight some of the more recent technological advances that have improved the efficiency of imaging mass spectrometry for clinical applications. Advances in the way MALDI mass spectrometry is integrated with histology, improved methods for automation, and better tools for data analysis are outlined in this review. The second review from Sweedler team [2] is focused on MALDI imaging techniques available to investigate the nervous system, with particular focus on the capability of MSI to examine both normal and diseased brain function. An important investigative tool, MSI offers tremendous potential in fundamental studies of brain chemistry, localization of pharmaceutical compounds, and the discovery of biomarkers for different neuropathologies. The third paper from Brunelle team [3] reviews the most recent advances in this field. After a short reminder of the basic physics involved, the instruments are described, as well as the primary ion sources, including the different cluster ion sources. The sample preparation methods are also described and compared, such as the matrix coating and the metal coating. The capabilities of the technique are finally illustrated with the most recent applications published in the last years. The fourth paper from Woods team [4] is devoted to MALDI MS analyses in positive ion mode to examine and contrast positively charged phospholipids which are mainly located in the outer cellular membranes and compare their make up in the following organs brain, liver, kidney and heart.Phosphatidylcholines in particular are zwitterionic as they have both a phosphate and aquaternary amine, which allows them to interact with aromatic compounds as well as compoundscontaining carboxyl, guanidinium, phosphate and sulfate groups. Phospholipids propensity forinteraction explains why so many small molecules and therapeutic compounds are stored inadipose tissue, or are detected interacting with cellular membranes. References [1] Wisztorski M, Lemaire R, Stauber J, Menguelet SA, Croix D, Mathe OJ, Day R, Salzet M, Fournier I. New Developments in MALDI Imaging for Pathology Proteomic Studies. Curr Pharm Des 2007; 13(32): 3317-3324. [2] Rubakhin SS, Hatcher NG, Monroe EB, Heien ML, Sweedler JV. Mass Spectrometric Imaging of the Nervous System. Curr Pharm Des 2007; 13(32): 3325-3334. [3] Brunelle A, Laprevote O. Recent Advances in Biological Tissue Imaging with Time-of-Flight Secondary Ion Mass Spectrometry: Polyatomic Ion Sources, Sample Preparation, and Applications. Curr Pharm Des 2007; 13(32): 3335-3343. [4] Woods AS, Wang H-YJ, Jackson SN. A Snapshot of Tissue Glycerolipids. Curr Pharm Des 2007; 13(32): 3344-3356.