Imaging mass spectrometry of steroids

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Imaging Mass Spectrometry (IMS) is a technology that provides information on the spatial distribution of biomolecules in thin tissue sections in direct correlation with the underlying histology. The potential of IMS analysis, in which the spatial distribution of biomolecules can be mapped throughout a tissue section, is particularly exciting for the study of neurodegenerative diseases. We propose herein to develop and optimize new methodologies for the selective on-tissue derivatization of steroids to facilitate their detection and quantitation by IMS. We will also develop micro-extraction, purification and quantitation methods to efficiently measure endogenous steroids in tissues by LC- (tandem) MS. Finally, with these MS assays, we envision identifying and quantifying several active steroids in cynomolgus monkey brain. The investigation of distributions and quantities of active steroids in control and chemically altered brain tissues will give us better insights into some of the mechanisms leading to Alzheimer's disease. Specifically, this project will shed some light on the contribution of peripheral DHEA (which may have a pharmaceutical value against Alzheimer's disease) in the production of neurosteroids. Overall, this R&D project should provide novel and much needed methods to the scientific community to accurately measure tissue levels of steroids by IMS and LC- (tandem) MS with applications in clinical research to monitor and understand the role of steroid hormones in numerous diseases, including neurodegenerative diseases and cancer. Such advances will facilitate the development of novel preventive therapies.