Quantitative Analysis and Mapping of Metals in Tissues

描述（由申请人提供）：本项目第二阶段的目标是开发和演示一种单色微x射线荧光（M¿XRF）仪器，用于高灵敏度和高空间分辨率（10-20米）绘制已故阿尔茨海默氏症研究对象人脑组织中的痕量金属分布。扫描后，将对脑组织切片进行染色，并在显微镜下检查A （β淀粉样蛋白）斑块、神经原纤维缠结和其他细胞异常，以检查相关性。研究对象在延长的死亡前处理和研究期间的全脑磁共振（MRI）测量和死后的全脑和相关组织切片的微MRI测量。这将包括迄今为止阿尔茨海默病（AD）最全面的相关金属-神经组织学研究。同样的仪器也可用于研究其他医用材料（如心脏、肝脏、肾脏、骨骼等）和环境、农业、工业、法医、科学或其他材料中的元素分布，通常不需要特殊的样品制备。目前的元素扫描技术在灵敏度（传统的微x射线荧光，电子微束），昂贵和/或难以获得（同步加速器微x射线荧光），或破坏性和复杂（聚焦离子束二次离子质谱和激光烧蚀电感耦合等离子体质谱）方面受到限制。紧凑，低功耗，经济实惠的微量元素测绘仪器是基于新的，强大的，专有的，单色双弯曲晶体（DCC） x射线光学技术开发的x射线光学系统公司，东格林布什，NY。由此产生的分析仪是一种安全、可靠、紧凑、易于操作的扫描仪器，可用于研究诊所的高分辨率（10-20¿m）元素空间分布测量。对社会的好处将是提高对20多种神经退行性疾病（AD， PD， ALS， MS, Wilson's disease, Huntington's disease等）特征的金属沉积物的作用的认识。用于骨铅、肾、心、肝等其他医学病理的研究以及法医、大气、地质、农业、化学、制药等其他领域，随着时间的推移，将大大拓宽医学、科学、工业和社会效益。该项目中开发的紧凑型、低功耗、经济实惠的微量元素测绘仪器是基于由纽约州东格林布什的x射线光学系统公司开发的新型专有x射线光学技术。由此产生的分析仪是一种安全、经济、可靠、紧凑、易于操作的扫描仪器，可用于脑组织切片的高分辨率（10-20 μ m）元素分布测量，并将提高对几乎所有已确定的神经退行性疾病（AD、PD、ALS、MS、威尔逊病、亨廷顿病等）伴随的脑金属沉积物作用的认识。类似用于骨铅、肾、心、肝等医学。研究以及在其他科学和工业应用中显示出具有重要社会效益的潜力。

DESCRIPTION (provided by applicant): The objectives of this Phase II project are to develop and demonstrate a monochromatic-micro-x-ray fluorescence (M¿XRF) instrument for high sensitivity and high spatial resolution (10-20 ¿m) 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 ¿m) 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 ¿m) 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.