Gray and white matter demyelination and remyelination detected with multimodal quantitative mri analysis at 11.7T in a chronic mouse model of multiple sclerosis

Abstract

Myelin is a component of the nervous system that is disrupted in multiple sclerosis, resulting in neuro-axonal degeneration. The longitudinal effect of chronic cuprizone-induced demyelination was investigated in the cerebral gray and white matter of treated mice and the spontaneous remyelination upon treatment interruption. Multimodal Magnetic Resonance Imaging and a Cryoprobe were used at 11.7T to measure signal intensity ratios, T2 values and diffusion metrics. The results showed significant and reversible modifications in white matter and gray matter regions such as in the rostral and caudal corpus callosum, the external capsule, the cerebellar peduncles, the caudate putamen, the thalamus, and the somatosensory cortex of treated mice. T2 and radial diffusivity metrics appeared to be more sensitive than fractional anisotropy, axial diffusivity or mean diffusivity to detect those cuprizone-induced changes. In the gray matter, only signal and T2S metrics and not diffusion metrics were sensitive to detect any changes. Immunohistochemical qualitative assessments in the same regions confirmed demyelination and remyelination processes. These multimodal data will provide better understanding of the dynamics of cuprizone-induced de- and remyelination in white and gray matter structures, and will be the basis to test therapies in experimental models.