High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron

We report R₂ and R₂* in human hippocampus from five unfixed post-mortem Alzheimer's disease (AD) and three age-matched control cases. Formalin-fixed tissues from opposing hemispheres in a matched AD and control were included for comparison. Imaging was performed in a 600 MHz (14 T) vertical bore magnet at MR microscopy resolution to obtain R₂ and R₂* (62 μm × 62 μm in-plane, 80 μm slice thickness), and R₁ at 250 μm isotropic resolution. R₁, R₂ and R₂* maps were computed for individual slices in each case, and used to compare subfields between AD and controls. The magnitudes of R₂ and R₂* changed very little between AD and control, but their variances in the Cornu Ammonis and dentate gyrus were significantly higher in AD compared for controls (p < 0.001). To investigate the relationship between tissue iron and MRI parameters, each tissue block was cryosectioned at 30 μm in the imaging plane, and iron distribution was mapped using synchrotron microfocus X-ray fluorescence spectroscopy. A positive correlation of R₂ and R₂* with iron was demonstrated. While studies with fixed tissues are more straightforward to conduct, fixation can alter iron status in tissues, making measurement of unfixed tissue relevant. To our knowledge, these data represent an advance in quantitative imaging of hippocampal subfields in unfixed tissue, and the methods facilitate direct analysis of the relationship between MRI parameters and iron. The significantly increased variance in AD compared for controls warrants investigation at lower fields and in-vivo, to determine if this parameter is clinically relevant.