During the acute phase of spinal cord injury (SCI), major alterations of white and grey matter are a key issue, which determine the neurological outcome. The present study with ex vivo quantitative high-field magnetic resonance microimaging (MRI) was intended in order to identify sensitive parameters of tissue disruption in a well-controlled mouse model of ischemic SCI. MR imaging evidenced changes as early as the second hour after the lesion in the dorsal horns, which appear swollen. After 4 h, alterations of the white matter of dorsal and lateral funiculi were reflected by a progressive loss of white/grey matter contrast with further ventral extension by the 24th hour. Diffusion tensor imaging and multi-exponential T2 measurements permitted to quantify these physicochemical, time-related, alterations during the 24-h period. This characterization of spatial and temporal evolution of SCI will contribute to better define both the most appropriate targets for future therapies and more accurate therapeutic windows. Upcoming directions include the use of these parameters on in vivo animal models and their application to clinics. Indeed, magnetic resonance techniques appear now as a major non-invasive translation tool in CNS pathologies based on the development of more appropriate pre-clinical models.