Passive staining: A novel ex vivo MRI protocol to detect amyloid deposits in mouse models of Alzheimer's disease

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Abstract
Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). This study evaluated a novel μMRI strategy based on “passive staining” of brain samples by gadoteric acid. The protocol was tested at 4.7T on control animals and APP/PS1 mice modeling AD lesions. T1 was strongly decreased in passively stained brains. On high‐resolution 3D gradient echo images, the contrast between the cortex and subcortical structures was highly improved due to a T2* effect. The brains of APP/PS1 mice revealed plaques as hypointense spots. They appeared larger in long compared to short TE images. This suggests that, after passive staining, plaques caused a susceptibility effect. This easily performed protocol is a complementary method to classic histology to detect the 3D location of plaques. It may also be used for the validation of in vivo MRI protocols for plaque detection by facilitating registration with histology via post mortem MRI. Magn Reson Med, 2006.