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Updated: Dec 12, 2025
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Sensitivity to myelin using model-free analysis of the water resonance line-shape in postmortem mouse brain
Sean Foxley1, Gregg Wildenberg2, Vandana Sampathkumar2
1Department of Radiology, University of Chicago, Chicago, Illinois, USA.
Purpose:
Dysmyelinating diseases are characterized by abnormal myelin formation and function. Such microstructural abnormalities in myelin have been demonstrated to produce measurable effects on the MR signal. This work examines these effects on measurements of voxel-wise, high-resolution water spectra acquired using a 3D echo-planar spectroscopic imaging (EPSI) pulse sequence from both postmortem fixed control mouse brains and a dysmyelination mouse brain model.
Methods:
Perfusion fixed, resected control (n = 5) and shiverer (n = 4) mouse brains were imaged using 3D-EPSI with 100 µm isotropic resolution. The free induction decay (FID) was sampled every 2.74 ms over 192 echoes, for a total sampling duration of 526.08 ms. Voxel-wise FIDs were Fourier transformed to produce water spectra with 1.9 Hz resolution. Spectral asymmetry was computed and compared between the two tissue types.
Results:
The water resonance is more asymmetrically broadened in the white matter of control mouse brain compared with dysmyelinated white matter. In control brain, this is modulated by and consistent with previously reported orientationally dependent effects of white matter relative to B0 . Similar sensitivity to orientation is observed in dysmyelinated white matter as well; however, the magnitude of the resonance asymmetry is much lower across all directions.
Conclusion:
Results demonstrate that components of the spectra are specifically differentially affected by myelin concentration. This suggests that water proton spectra may be sensitive to the presence of myelin, and as such, could serve as a MRI-based biomarker of dysmyelinating disease, free of mathematical models.
Insights
This study shows that MRI water spectra can detect myelin differences in mouse brains, suggesting a new biomarker for dysmyelinating diseases without complex models.
Area of Science:
- Neuroimaging
- Biomarker Discovery
- Myelin Biology
Background:
- Dysmyelinating diseases involve abnormal myelin formation and function.
- These abnormalities impact the magnetic resonance (MR) signal.
- Investigating these MR signal effects is crucial for understanding disease mechanisms.
Purpose of the Study:
- To examine the effects of myelin abnormalities on voxel-wise, high-resolution water spectra.
- To compare these spectral measurements between control and dysmyelination mouse brain models.
- To assess the potential of water spectra as an MRI-based biomarker for dysmyelinating diseases.
Main Methods:
- Utilized 3D echo-planar spectroscopic imaging (EPSI) with 100 µm isotropic resolution on control (n=5) and shiverer (n=4) mouse brains.
- Acquired free induction decay (FID) data over 192 echoes (526.08 ms total sampling duration).
- Computed and compared spectral asymmetry from voxel-wise FIDs after Fourier transformation.
Main Results:
- White matter water resonance showed greater asymmetry in control brains compared to dysmyelinated brains.
- Orientation-dependent effects on white matter resonance were observed in both groups.
- The magnitude of resonance asymmetry was significantly lower in dysmyelinated white matter across all orientations.
Conclusions:
- Components of water proton spectra are differentially affected by myelin concentration.
- Water proton spectra show sensitivity to myelin presence, indicating potential as an MRI biomarker.
- This approach may offer a model-free method for diagnosing dysmyelinating diseases.
