Wadghiri Youssef Zaim, Sigurdsson Einar M, Wisniewski Thomas, Turnbull Daniel H
Skirball Institute of Biomolecular Medicine and Department of Radiology, New York University School of Medicine, NY, USA.
Methods Mol Biol. 2005;299:365-79. doi: 10.1385/1-59259-874-9:365.
Transgenic mice are used increasingly to model brain amyloidosis, mimicking the pathogenic processes involved in Alzheimer's disease (AD). In this chapter, a strategy is described that has been successfully used to map amyloid deposits in transgenic mouse models of AD with magnetic resonance imaging (MRI), utilizing molecular targeting vectors labeled with MRI contrast agents to enhance selectively the signal from amyloid plaques. To obtain sufficient spatial resolution for effective and sensitive mouse brain imaging, magnetic fields of 7-Tesla (T) or more are required. These are higher than the 1.5-T field strength routinely used for human brain imaging. The higher magnetic fields affect contrast agent efficiency, and determine the choice of pulse sequence parameters for in vivo MRI, all addressed in this chapter. Ex vivo imaging is also described as an important step to test and optimize protocols prior to in vivo studies. The experimental setup required for mouse brain imaging is explained in detail, including anesthesia, immobilization of the mouse head to reduce motion artifacts, and anatomical landmarks to use for the slice alignment procedure to improve image co-registration during longitudinal studies, and for subsequent matching of MRI with histology.
转基因小鼠越来越多地被用于模拟脑淀粉样变性,以模仿阿尔茨海默病(AD)所涉及的致病过程。在本章中,将描述一种已成功用于通过磁共振成像(MRI)在AD转基因小鼠模型中绘制淀粉样蛋白沉积物的策略,该策略利用用MRI造影剂标记的分子靶向载体来选择性增强淀粉样斑块的信号。为了获得足够的空间分辨率以进行有效且灵敏的小鼠脑成像,需要7特斯拉(T)或更高的磁场。这些磁场高于常规用于人脑成像的1.5-T场强。更高的磁场会影响造影剂效率,并决定体内MRI脉冲序列参数的选择,本章将对所有这些内容进行阐述。离体成像也被描述为在体内研究之前测试和优化方案的重要步骤。详细解释了小鼠脑成像所需的实验设置,包括麻醉、固定小鼠头部以减少运动伪影,以及在纵向研究期间用于切片对齐程序以改善图像配准的解剖标志,以及用于随后将MRI与组织学匹配的解剖标志。