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Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia
Published on: September 20, 2015
MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice
Philip R Holland1, Mark E Bastin, Maurits A Jansen
1Centre for Cognitive Ageing and Cognitive Epidemiology, Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, UK. philip.holland@ed.ac.uk
Abstract:
White matter (WM) abnormalities, possibly resulting from hypoperfusion, are key features of the aging human brain. It is unclear, however, whether in vivo magnetic resonance imaging (MRI) approaches, such as diffusion tensor and magnetization transfer MRI are sufficiently sensitive to detect subtle alterations to WM integrity in mouse models developed to study the aging brain. We therefore investigated the use of diffusion tensor and magnetization transfer MRI to measure structural changes in 4 WM tracts following 1 month of moderate hypoperfusion, which results in diffuse WM pathology in C57Bl/6J mice. Following MRI, brains were processed for evaluation of white and gray matter pathology. Significant reductions in fractional anisotropy were observed in the corpus callosum (p = 0.001) and internal capsule (p = 0.016), and significant decreases in magnetization transfer ratio were observed in the corpus callosum (p = 0.023), fimbria (p = 0.032), internal capsule (p = 0.046) and optic tract (p = 0.047) following hypoperfusion. Hypoperfused mice demonstrated diffuse axonal and myelin pathology which was essentially absent in control mice. Both fractional anisotropy and magnetization transfer ratio correlate with markers of myelin integrity/degradation and not axonal pathology. The study demonstrates that in vivo MRI is a sensitive measure of diffuse, subtle WM changes in the murine brain.
Insights
In vivo MRI detects subtle white matter (WM) changes in aging mouse brains. Diffusion tensor and magnetization transfer MRI show WM integrity alterations following hypoperfusion, correlating with myelin damage.
Area of Science:
- Neuroimaging
- Neuroscience
- Biomedical Engineering
Background:
- White matter (WM) abnormalities are characteristic of aging brains, potentially due to hypoperfusion.
- The sensitivity of in vivo magnetic resonance imaging (MRI) techniques for detecting subtle WM changes in aging mouse models remains unclear.
Purpose of the Study:
- To evaluate diffusion tensor MRI (DT-MRI) and magnetization transfer MRI (MT-MRI) for detecting structural alterations in WM following induced hypoperfusion in mice.
- To assess the correlation between MRI findings and neuropathological markers of axonal and myelin integrity.
Main Methods:
- C57Bl/6J mice underwent 1 month of moderate hypoperfusion.
- In vivo DT-MRI and MT-MRI were performed to measure WM integrity in specific tracts.
- Brain tissue was pathologically examined for axonal and myelin damage.
Main Results:
- Significant reductions in fractional anisotropy (FA) were found in the corpus callosum and internal capsule.
- Magnetization transfer ratio (MTR) significantly decreased in the corpus callosum, fimbria, internal capsule, and optic tract.
- MRI metrics (FA and MTR) correlated with myelin integrity markers, not axonal pathology, and hypoperfused mice showed significant WM pathology.
Conclusions:
- In vivo DT-MRI and MT-MRI are sensitive tools for detecting subtle, diffuse white matter changes in the aging murine brain.
- These MRI techniques can identify hypoperfusion-induced WM pathology, specifically related to myelin integrity.
