Quantitative Analysis and Mapping of Metals in Tissues

DESCRIPTION (provided by applicant): The objectives of this Phase II project are to develop and demonstrate a monochromatic-micro-x-ray fluorescence (MfXRF) instrument for high sensitivity and high spatial resolution (10-20 fm) mapping of trace metal distributions in human brain tissue from deceased Alzheimer's research subjects. After scanning, the brain tissue sections will be stained and microscopically examined for A (beta amyloid) plaque, neurofibrillary tangles and other cellular abnormalities to examine correlations. Whole brain magnetic resonance (MRI) measurements on the research subject during extended pre-death treatment and study and post-mortem whole brain and micro MRI measurements of related tissue sections. This will comprise the most comprehensive correlated metal-neurohistological study of Alzheimer's disease (AD) to date. The same instrument can also be used to study elemental distributions in other medical materials (e.g. heart, liver, kidney, bone, etc.), and environmental, agricultural, industrial, forensic, scientific or other materials, often with no special sample preparation. Current elemental scanning technologies are limited in sensitivity (conventional micro x- ray fluorescence, electron microbeam), expensive and/or inaccessible (Synchrotron micro x-ray fluorescence), or destructive and complex (focused ion beam secondary ion mass spectrometry and laser ablation inductively coupled plasma mass spectrometry). The compact, low power, affordable trace element mapping instrument is based on new, powerful, proprietary, monochromatic doubly curved crystal (DCC) x-ray optics technology developed by X-Ray Optical Systems, Inc., East Greenbush, NY. The resulting analyzer is a safe, reliable, compact, easy to operate, scanning instrument for use in the research clinic for high resolution (10-20 fm) elemental spatial distribution measurements. The benefit to society will be improved knowledge of the role of metal deposits which characterize more than 20 defined neurodegenerative diseases (AD, PD, ALS, MS, Wilson's disease, Huntington's disease, etc.). Use in bone lead, renal, heart, liver, etc. studies of other medical pathologies and in other fields such as forensic, atmospheric, geological, agricultural, chemical, pharmaceutical etc. will, over time, greatly broaden the medical, scientific, industrial and social benefits. Tissue mapping proposal narrative The compact, low power, affordable trace element mapping instrument to be developed in this project is based on new, proprietary, x-ray optics technology developed by X-Ray Optical Systems, Inc., East Greenbush, NY. The resulting analyzer is a safe, affordable, reliable, compact, easy to operate, scanning instrument for high resolution (10-20 fm) elemental distribution measurements in brain tissue sections and will give improved knowledge of the role of brain metal deposits which accompany virtually every identified neurodegenerative disease (AD, PD, ALS, MS, Wilson's disease, Huntington's disease, etc.). Similar use in bone lead, renal, heart, liver, and other medical. studies and in other scientific, and industrial applications show potential for important societal benefit.