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P2‐002: Detection of amyloid plaques by diffraction enhanced imaging in a mouse model of Alzheimer's disease
Author(s) -
Connor Dean M.,
Benveniste Helene,
Dilmanian Avraham,
Miller Lisa,
Kritzer Mary F.,
Zhong Zhong
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1082
Subject(s) - white matter , pathology , hippocampal formation , refraction , anatomy , biology , magnetic resonance imaging , medicine , neuroscience , optics , radiology , physics
Background: Diffraction enhanced imaging (DEI) is a new imaging modality that generates contrast from the refraction of -rays. DEI’s images show enhanced soft tissue contrast as compared to conventional radiography. Objective: We tested the hypothesis that amyloid deposits (A plaques), one of the hallmarks of Alzheimer’s disease (AD), can be visualized by DEI when applied in the micro-computed tomography (microCT) mode. Methods: Formalin-fixed brains excised from the skull of AD-model [B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J, male, 6 months] and age-matched wild-type mouse brains were imaged whole using 20 keV -rays on the DEI system at the National Synchrotron Light Source. Volumetric refraction microCT data sets of the mouse brains were generated with a voxel size of 9 m. Post-imaging, the brains were sectioned using a cryotome and immunostained to mark the A plaques. Images from the refraction microCT data set were compared to the corresponding digitized histological sections using anatomical landmarks and processing software. Several anatomical structures within the brain, such as hippocampal subregions and white matter tracks, were visualized. Importantly, structures resembling small ‘nodules’ were seen in the refraction microCT images of the AD-model mouse brain but not in the wild-type brain. The size and physical density of the nodules were measured and compared to A plaques on the histological sections. Results: Histological stained brain sections corresponding to the refraction microCT slice images demonstrated that the nodule-like structures in the cortex and hippocampus of the ADmodel mouse brain corresponded to locations of A plaques. The size of the plaques, as determined from the refraction microCT data, was 44 13 m. The difference in density between the plaques and the surrounding brain tissue was 21 4 mg/cc. Conclusions: We have demonstrated that the DEI technique can be used both to visualize A plaques and measure their density. As such, it provides novel physical information which is not currently available with other imaging techniques. This technique can be extended to in vivo imaging of mice allowing for tracking and characterizing A plaques over time.