Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging

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.

Figure 1:

Mean ± standard deviation of estimates for, A, B, axon diameter; C, D, restricted fraction; E, F, free water fraction; and, G, H, axon density in the six healthy control subjects and six patients with MS within ROIs drawn in NAWM in the genu, body, and splenium of the midline sagittal section of the corpus callosum in the patients with MS and in similar locations in the healthy control subjects. The estimates for axon diameter (B), restricted fraction (D), free water fraction (F), and axon density (H) within the lesion for each patient with MS are indicated as bars with hatch marks and are color coded to match the location of the corresponding normal-appearing areas of the corpus callosum.

Figure 2:

Sagittal FLAIR images (top row) and voxelwise maps of axon diameter (second row), restricted fraction (third row), and axon density (bottom row) in the midline corpus callosum in the six patients with MS. Lesions can be seen on FLAIR images (red arrows) and voxelwise maps (white arrows). Lesions show increased axon diameter and decreased restricted fraction and axon density, as compared with the adjacent NAWM.

Figure 3:

Sagittal axon diameter map (top image) shows representative voxels in the, A, genu; B, body; C, lesion; and, D, splenium of the midline corpus callosum in a patient with MS (patient 3) and corresponding diffusion-weighted data and fitted signal decays for different q and diffusion times. The solid lines represent the predicted signals from the fitted model. All measurements were normalized by an estimate of S₀, the signal obtained without diffusion weighting (b = 0).