Characterizing Structural Changes With Devolving Remyelination Following Experimental Demyelination Using High Angular Resolution Diffusion MRI and Texture Analysis

Background: Changes in myelin integrity are associated with the pathophysiology of many neurological diseases, including multiple sclerosis. However, noninvasive measurement of myelin injury and repair remains challenging. Advanced MRI techniques including diffusion tensor imaging (DTI), neurite orientation dispersion and density index (NODDI), and texture analysis have shown promise in quantifying subtle abnormalities in white matter structure.

Purpose: To determine whether and how these advanced imaging methods help understand remyelination changes after demyelination using a mouse model.

Study type: Prospective, longitudinal.

Animal model: Demyelination was induced in the thoracic spinal cord of 21 mice using the chemical toxin lysolecithin.

Field strength/sequences: 9.4T ASSESSMENT: Imaging was done at day 7 (demyelination) and days 14 to 35 (ongoing remyelination) postsurgery, followed by histology. Image analysis focused on both lesions and peri-lesional areas where remyelination began. In histology, we quantified the complexity of tissue alignment using angular entropy, in addition to staining area.

Statistical analysis: Two-way analysis of variance was performed for assessing differences between tissue types and across timepoints, followed by post-hoc analysis to correct for multiple comparisons (P < 0.05).

Results: All diffusion and texture parameters were worse in lesions than the control tissue (P < 0.05) except orientation dispersion index (ODI) and neurite density index (NDI) over late remyelination. Longitudinally, ODI decreased and NDI increased persistently in both lesions and peri-lesion regions (P < 0.05). Fractional anisotropy showed a mild decrease at day 35 after increase, when lesion texture heterogeneity showed a trend to decrease (P > 0.05). Both lesion size and angular entropy decreased over time, and no change in any measure in the control tissue.

Data conclusion: Diffusion and MRI texture metrics may provide compensatory information on myelin repair and ODI and NDI could be sensitive measures of evolving remyelination, deserving further validation.

Level of evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1750-1759.