Detection of neuritic plaques in Alzheimer's disease by magnetic resonancemicroscopy

Magnetic resonance microscopy (MRM) theoretically provides the spatial reso lution and signal-to-noise ratio needed to resolve neuritic plaques, the ne uropathological hallmark of Alzheimer's disease (AD). Two previously unexpl ored MR contrast parameters, T2* and diffusion, are tested for plaque-speci fic contrast to noise. Autopsy specimens from nondemented controls (n = 3) and patients with AD (n = 5) were used. Three-dimensional T2* and diffusion MR images with voxel sizes ranging from 3 x 10(-3) mm(3) to 5.9 x 10(-5) m m(3) were acquired. After imaging, specimens were cut and stained with a mi crowave king silver stain to demonstrate neuritic plaques. From controls, t he alveus, fimbria, pyramidal cell layer, hippocampal sulcus, and granule c ell layer were detected by either T2* or diffusion contrast. These structur es were used as landmarks when correlating MRMs with histological sections. At a voxel resolution of 5.9 x 10(-5) mm(3), neuritic plaques could be det ected by T2*. The neuritic plaques emerged as black, spherical elements on T2* MRMs and could be distinguished from vessels only in cross-section when presented in three dimension. Here we provide MR images of neuritic plaque s in vitro. The MRM results reported provide a new direction for applying t his technology in vivo. Clearly, the ability to detect and follow the early progression of amyloid-positive brain lesions will greatly aid and simplif y the many possibilities to intervene pharmacologically in AD.