title: High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron.
abstract: We report R(2) and R(2) 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 600MHz (14T) vertical bore magnet at MR microscopy resolution to obtain R(2) and R(2) (62 μm×62 μm in-plane, 80 μm slice thickness), and R(1) at 250 μm isotropic resolution. R(1), R(2) and R(2) maps were computed for individual slices in each case, and used to compare subfields between AD and controls. The magnitudes of R(2) and R(2) 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 R(2) and R(2)* 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.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Antharam
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Collingwood
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Bullivant
authors.forename: Mark R
authors.initials: MR
authors.lastname: Davidson
authors.forename: Saurav
authors.initials: S
authors.lastname: Chandra
authors.forename: Albina
authors.initials: A
authors.lastname: Mikhaylova
authors.forename: Mary E
authors.initials: ME
authors.lastname: Finnegan
authors.forename: Christopher
authors.initials: C
authors.lastname: Batich
authors.forename: John R
authors.initials: JR
authors.lastname: Forder
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D002102:Cadaver; D005260:Female; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008853:Microscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D014018:Tissue Distribution
chemical_list: D007501:Iron