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

DOI: 10.1016/j.neuroimage.2011.08.019 DOI Help
PMID: 21867761 PMID Help

Authors: Vijay Antharam (University of Florida) , Joanna Collingwood (Keele University) , John-paul Bullivant (University of Florida) , Mark R. Davidson (University of Florida) , Saurav Chandra (University of Florida) , Albina Mikhaylova (University of Florida) , Mary E. Finnegan (University of Warwick) , Christopher Batich (University of Florida) , John R. Forder (University of Florida) , Jon Dobson (Keele University; University of Florida)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Neuroimage

State: Published (Approved)
Published: August 2011
Diamond Proposal Number(s): 614

Abstract: 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 ?m × 62 ?m in-plane, 80 ?m slice thickness), and R1 at 250 ?m 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 ?m 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.

Journal Keywords: Human; Hippocampus; Alzheimer's disease; MRI; Iron; Variance

Subject Areas: Technique Development, Medicine, Engineering

Instruments: I18-Microfocus Spectroscopy