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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2020

Open Access 01-12-2020 | Magnetic Resonance Imaging | Research

The brains of aged mice are characterized by altered tissue diffusion properties and cerebral microbleeds

Authors: Erik N. Taylor, Nasi Huang, Jonathan Wisco, Yandan Wang, Kathleen G. Morgan, James A. Hamilton

Published in: Journal of Translational Medicine | Issue 1/2020

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Abstract

Background

Brain aging is a major risk factor in the progression of cognitive diseases including Alzheimer’s disease (AD) and vascular dementia. We investigated a mouse model of brain aging up to 24 months old (mo).

Methods

A high field (11.7T) MRI protocol was developed to characterize specific features of brain aging including the presence of cerebral microbleeds (CMBs), morphology of grey and white matter, and tissue diffusion properties. Mice were selected from age categories of either young (3 mo), middle-aged (18 mo), or old (24 mo) and fed normal chow over the duration of the study. Mice were imaged in vivo with multimodal MRI, including conventional T2-weighted (T2W) and T2*-weighted (T2*W) imaging, followed by ex vivo diffusion-weighted imaging (DWI) and T2*W MR-microscopy to enhance the detection of microstructural features.

Results

Structural changes observed in the mouse brain with aging included reduced cortical grey matter volume and enlargement of the brain ventricles. A remarkable age-related change in the brains was the development of CMBs found starting at 18 mo and increasing in total volume at 24 mo, primarily in the thalamus. CMBs presence was confirmed with high resolution ex vivo MRI and histology. DWI detected further brain tissue changes in the aged mice including reduced fractional anisotropy, increased radial diffusion, increased mean diffusion, and changes in the white matter fibers visualized by color-coded tractography, including around a large cortical CMB.

Conclusions

The mouse is a valuable model of age-related vascular contributions to cognitive impairment and dementia (VCID). In composite, these methods and results reveal brain aging in older mice as a multifactorial process including CMBs and tissue diffusion alterations that can be well characterized by high field MRI.
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Metadata
Title
The brains of aged mice are characterized by altered tissue diffusion properties and cerebral microbleeds
Authors
Erik N. Taylor
Nasi Huang
Jonathan Wisco
Yandan Wang
Kathleen G. Morgan
James A. Hamilton
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02441-6

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