Small-angle x-ray scattering (SAXS) imaging may have the potential to image β amyloid plaques in vivo in the brain without tracers for assessment of Alzheimer's disease (AD). We use a laboratory SAXS system for planar imaging of AD model and control mouse brains slices to detect regions with high density of amyloid plaques. These regions were validated with histology methods. Using Monte Carlo techniques, we simulate SAXS computed tomography (SAXS-CT) system to study the potential of selectively differentiating amyloid targets in mouse and human head phantoms with detailed anatomy. We found contrast between amyloid and brain tissue at small q (below 0.8 nm-1) in the neocortex region of the transgenic brain slices as supported by histology. We observed similar behavior through planar SAXS imaging of an amyloid-like fibril deposit with a 0.8 mm diameter at a known location on a wild type mouse brain. In our SAXS-CT simulations, we found that 33-keV x rays provide increase plaque visibility in the mouse head for targets of at least 0.1 mm in diameter, while in the human head, 70-keV x rays were capable of detecting plaques as small as 2 mm. To increase radiation efficiency, we used a weighted-sum image visualization approach allowing the dose deposited by 70-keV x rays per SAXS-CT slice of the human head to be reduced by a factor of 10 to 71 mGy for gray matter and 63 mGy for white matter. The findings suggest that a dedicated SAXS-CT system for in vivo amyloid imaging in small animals and humans can be successfully developed with further system optimization to detect regions with amyloid plaques in the brain with a safe level of radiation dose.

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使用小角度 X 射线散射对大脑中淀粉样蛋白成像的可行性

小角度 X 射线散射 (SAXS) 成像可能有可能在大脑中对 β 淀粉样蛋白斑块进行体内成像，而无需示踪剂来评估阿尔茨海默病 (AD)。我们使用实验室 SAXS 系统对 AD 模型进行平面成像，并控制小鼠大脑切片以检测具有高密度淀粉样斑块的区域。这些区域用组织学方法验证。我们使用蒙特卡罗技术模拟 SAXS 计算机断层扫描 (SAXS-CT) 系统，以研究选择性区分具有详细解剖结构的小鼠和人类头部幻影中的淀粉样蛋白靶标的潜力。我们在组织学支持的转基因脑切片的新皮层区域中发现淀粉样蛋白和脑组织在小 q（低于 0.8 nm-1）处的对比。我们通过平面 SAXS 成像观察到类似的行为，淀粉样原纤维沉积物为 0。8 毫米直径在野生型小鼠大脑的已知位置。在我们的 SAXS-CT 模拟中，我们发现 33 keV x 射线可提高小鼠头部对直径至少为 0.1 毫米的目标的斑块可见性，而在人头部，70 keV x 射线能够检测斑块，如小至 2 毫米。为了提高辐射效率，我们使用了一种加权和图像可视化方法，允许将 70 keV x 射线沉积的剂量降低到每个人头部的 SAXS-CT 切片的 10 到 71 mGy，对于灰质和 63 mGy对于白质。研究结果表明，通过进一步优化系统，可以成功开发出用于小动物和人类体内淀粉样蛋白成像的专用 SAXS-CT 系统，以在安全的辐射剂量水平下检测大脑中存在淀粉样蛋白斑块的区域。