This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This proposal presents a new direction for imaging transition metals in brain with direct relevance to human health. The technique of x-ray fluorescence spectroscopic mapping (XRF) is well-established but previous XRF images of metals in brain have probed a few very small tissue areas with micron-scale resolution. We propose a new approach for this field, in using a moderate resolution (50?m) and scanning a very large area in a short amount of time. As we show, such a large format image provides a wealth of information not achievable by micron-scale XRF. We build upon technology developed at SSRL by Uwe Bergmann and Martin George to enable rapid scanning of the Archimedes Palimpsest. In essence the sample is raster scanned with continuous motor motion and detectors are read on the fly with count times of ~10 msec (conventional XRF is ~1 sec). Excellent sensitivity is achievable at greatly increased scan speed. In 2006, we used this system to map physiological levels of Fe and Zn in slices of whole human and rodent brain. Building on this success, the three long-term goals of this program focus on metals in the brain with direct relevance to human health: 1. Improve the interpretation of magnetic resonance imaging (MRI);2. Understand the role of metals in neurodegeneration with a focus on Parkinson?s disease (PD), Friedreich?s ataxia (FRDA) and Wilson?s disease (WD);3. Advance the use of stem cells for brain and tissue repair.
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