Center for Devices and Radiological Health, FDA, Silver Spring, MD, United States of America.
Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States of America.
Biomed Phys Eng Express. 2020 Nov 27;7(1). doi: 10.1088/2057-1976/ab501c.
Small-angle x-ray scattering (SAXS) imaging may have the potential to image-amyloid plaquesin 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(below 0.8 nm) 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 foramyloid 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.
小角 X 射线散射 (SAXS) 成像有可能在不使用示踪剂的情况下对大脑中的淀粉样斑块进行成像，从而评估阿尔茨海默病 (AD)。我们使用实验室 SAXS 系统对 AD 模型和对照小鼠脑切片进行平面成像，以检测具有高淀粉样斑块密度的区域。这些区域通过组织学方法进行了验证。使用蒙特卡罗技术，我们模拟了 SAXS 计算机断层扫描 (SAXS-CT) 系统，以研究在具有详细解剖结构的小鼠和人头部体模中选择性区分淀粉样靶标的潜力。我们发现，在转 AD 基因的脑切片的新皮层区域，SAXS 与组织学支持的淀粉样斑块具有小的（低于 0.8nm）对比度。我们通过在野生型小鼠大脑的已知位置上对直径为 0.8mm 的类似淀粉样原纤维沉积物进行平面 SAXS 成像观察到了类似的行为。在我们的 SAXS-CT 模拟中，我们发现 33keV X 射线为直径至少为 0.1mm 的目标提供了在小鼠头部增加斑块可见度，而在人类头部，70keV X 射线能够检测到直径小至 2mm 的斑块。为了提高辐射效率，我们使用了加权和图像可视化方法，使 70keV X 射线在人类头部的每一个 SAXS-CT 切片上沉积的剂量减少 10 倍，对于灰质为 71mGy，对于白质为 63mGy。研究结果表明，可以成功开发用于小动物和人类的专用 SAXS-CT 系统来进行淀粉样成像，通过进一步的系统优化，使用安全的辐射剂量来检测大脑中的淀粉样斑块区域。
