AUTHOR=Maharjan Surendra , Tsai Andy P. , Lin Peter B. , Ingraham Cynthia , Jewett Megan R. , Landreth Gary E. , Oblak Adrian L. , Wang Nian 

TITLE=Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.964654

DOI=10.3389/fnins.2022.964654

ISSN=1662-453X

ABSTRACT=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 m. The b value was 3000 s/mm2 for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 m 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 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 months and 12 months 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.