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Updated: Mar 26, 2026

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging
Susie Y Huang1, Sean M Tobyne1, Aapo Nummenmaa1
1From the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129 (S.Y.H., A.N., T.W., L.L.W.); Department of Neurology, Massachusetts General Hospital, Boston, Mass (S.M.T., E.C.K.); and Richard M. Lucas Center for Imaging, Department of Radiology, Stanford University, Stanford, Calif (J.A.M.).
Abstract:
Purpose To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intra-axonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results MS lesions showed increased mean axon diameter (10.3 vs 7.9 μm in the genu, 10.4 vs 9.3 μm in the body, and 10.6 vs 8.2 μm in the splenium; P < .05) and decreased axon density ([0.48 vs 1.1] × 10(10)/m(2) in the genu, [0.40 vs 0.70] × 10(10)/m(2) in the body, and [0.35 vs 1.1] × 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. (©) RSNA, 2016 Online supplemental material is available for this article.
Insights
High-gradient diffusion MRI effectively depicts axonal damage in multiple sclerosis (MS) lesions by showing increased axon diameter and decreased density. This advanced imaging technique aids in understanding MS neuropathology.
Area of Science:
- Neuroimaging
- Radiology
- Biophysics
Background:
- Multiple Sclerosis (MS) is a demyelinating disease affecting the central nervous system.
- Axonal damage is a key factor in MS-related disability.
- Accurate depiction of axonal integrity is crucial for understanding MS progression.
Purpose of the Study:
- To evaluate high-gradient diffusion magnetic resonance (MR) imaging (up to 300 mT/m) for depicting axonal disease in MS lesions and normal-appearing white matter (NAWM).
- To compare high-gradient diffusion MR findings in MS patients with healthy controls.
Main Methods:
- Prospective study involving six MS patients and six healthy controls.
- Diffusion-weighted imaging using a 3-T MR imager with gradient strengths up to 300 mT/m.
- Modeling of intra-axonal, extra-axonal, and free water diffusion to estimate axon diameter and density.
Main Results:
- MS lesions exhibited significantly increased mean axon diameter (P < .05) and decreased axon density (P < .05) compared to adjacent NAWM.
- No significant differences in axon diameter or density were found between NAWM in MS patients and white matter in healthy controls.
Conclusions:
- High-gradient diffusion MR imaging (up to 300 mT/m) can characterize axonal disease in MS.
- Findings align with neuropathologic data, showing increased axon diameter and decreased axon density in MS lesions versus NAWM.

