Quantitative Analysis and Mapping of Metals in Tissues

描述（由申请人提供）：该第二阶段项目的目标是开发和演示一种单色微X射线荧光（M <$XRF）仪器，用于对已故阿尔茨海默氏症研究受试者的人脑组织中的痕量金属分布进行高灵敏度和高空间分辨率（10-20 <$m）绘图。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、神经元缠结和其他细胞异常，以检查相关性。在延长的死前治疗和研究期间对研究受试者进行全脑磁共振（MRI）测量，以及对相关组织切片进行尸检全脑和显微MRI测量。这将包括迄今为止最全面的阿尔茨海默病（AD）相关金属神经组织学研究。该仪器还可用于研究其他医学材料（例如心脏、肝脏、肾脏、骨骼等）中的元素分布，和环境、农业、工业、法医、科学或其他材料的样品，通常没有特殊的样品制备。目前的元素扫描技术在灵敏度（常规微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。这款紧凑、低功耗、经济实惠的微量元素绘图仪基于由X-Ray Optical Systems，Inc.开发的新型、功能强大、专有、单色双曲面晶体（DCC）X射线光学技术，纽约州东格林布什。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，可用于研究诊所进行高分辨率（10-20 μ m）元素空间分布测量。对社会的益处将是提高对金属沉积物作用的认识，金属沉积物表征了20多种定义的神经退行性疾病（AD、PD、ALS、MS、威尔逊病、亨廷顿病等）。随着时间的推移，在骨铅、肾脏、心脏、肝脏等其他医学病理学研究以及法医、大气、地质、农业、化学、制药等其他领域的使用将大大扩大医疗、科学、工业和社会效益。本项目中开发的紧凑型、低功耗、经济实惠的微量元素标测仪器基于由X射线光学系统公司开发的新型专有X射线光学技术，纽约州东格林布什。所得到的分析仪是一种安全、经济、可靠、紧凑、易于操作的扫描仪器，用于高分辨率（10-20 μ m）脑组织切片中的元素分布测量，并将提高对脑金属沉积物作用的认识，这些金属沉积物几乎伴随着每一种已确定的神经退行性疾病（AD、PD、ALS、MS、威尔逊病、亨廷顿病等）。在骨铅、肾脏、心脏、肝脏等医疗中也有类似用途。研究和其他科学和工业应用显示出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.