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Publication : Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging.

First Author  Maharjan S Year  2022
Journal  Front Neurosci Volume  16
Pages  964654 PubMed ID  36061588
Mgi Jnum  J:328309 Mgi Id  MGI:7335472
Doi  10.3389/fnins.2022.964654 Citation  Maharjan S, et al. (2022) Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging. Front Neurosci 16:964654
abstractText  Purpose: To evaluate the age-dependent microstructure changes in 5xFAD mice using high-resolution diffusion tensor imaging (DTI). Methods: The 5xFAD mice at 4, 7.5, and 12 months and the wild-type controls at 4 months were scanned at 9.4T using a 3D echo-planar imaging (EPI) pulse sequence with the isotropic spatial resolution of 100 mum. The b-value was 3000 s/mm(2) for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 mum isotropic resolution. The microstructure changes were quantified with DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD). The conventional histology was performed to validate with MRI findings. Results: The FA values (p = 0.028) showed significant differences in the cortex between wild-type (WT) and 5xFAD mice at 4 months, while hippocampus, anterior commissure, corpus callosum, and fornix showed no significant differences for either FA and MD. FA values of 5xFAD mice gradually decreased in cortex (0.140 +/- 0.007 at 4 months, 0.132 +/- 0.008 at 7.5 months, 0.126 +/- 0.013 at 12 months) and fornix (0.140 +/- 0.007 at 4 months, 0.132 +/- 0.008 at 7.5 months, 0.126 +/- 0.013 at 12 months) with aging. Both FA (p = 0.029) and MD (p = 0.037) demonstrated significant differences in corpus callosum between 4 and 12 months age old. FA and MD were not significantly different in the hippocampus or anterior commissure. The age-dependent microstructure alterations were better captured by FA when compared to MD. Conclusion: FA showed higher sensitivity to monitor amyloid deposition in 5xFAD mice. DTI may be utilized as a sensitive biomarker to monitor beta-amyloid progression for preclinical studies.
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