High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron
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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.
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MRI scans of post-mortem human brains and a mouse model of Alzheimer's disease show decreases in hippocampal T2* MRI, which is sensitive to the magnetic properties of iron or its spatial variance, attributed in part to iron in Aβ plaques.
“MRI scans of post-mortem human brains and a mouse model of Alzheimer’s disease show decreases in hippocampal T2* MRI, which is sensitive to the magnetic properties of iron86,87 or its spatial variance, attributed in part to iron in Aβ plaques.88–90”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [90]
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- Authors
- Antharam, V., Collingwood, J. F., Bullivant, J.-P., Davidson, M. R., Chandra, S., Mikhaylova, A., Finnegan, M. E., Batich, C., Forder, J. R., & Dobson, J.
- Affiliations
- University of Florida (US)
- University of Warwick (GB)
- University of Florida Health (US)
- Corresponding author
- Collingwood, Joanna F.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 59
- Issue
- 2
- Pages
- 1249-1260
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3690369
- OpenAlex
- W2091460820
- Cited by
- 82
- References
- 67
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 10 · 2016: 12 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 3
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (1R21NS060304-01, 1UL1RR029890)
- EPSRC LSI Postdoctoral Fellowship (EP/D066654/1)
- RCUK Academic Fellowship
- Royal Society Wolfson Research Merit Award
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, hippocampus, R2* mapping, R1 mapping, tissue iron, iron distribution, hippocampal subfields, cornu ammonis, dentate gyrus, unfixed tissue, postmortem brain, quantitative MRI
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cadaver, Female, Hippocampus, Humans, Iron, Magnetic Resonance Imaging, Male, Microscopy, Sensitivity and Specificity, Statistics as Topic, Tissue Distribution, Reproducibility of Results
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