Longitudinal assessment of white matter pathology in the injured mouse spinal cord through ultra-high field (16.4 T) in vivo diffusion tensor imaging

This study examined the sensitivity of ultra-high field (16.4 T) diffusion tensor imaging (DTI; 70 mu m in-plane resolution, 1 mm slice thickness) to evaluate the spatiotemporal development of severe mid-thoracic contusive spinal cord injury (SCI) in mice. In vivo imaging was performed prior to SCI, then again at 2 h, 1 day, 3 days, 7 days, and 30 days post-SCI using a Bruker 16.4 T small animal nuclear magnetic resonance spectrometer. Cross-sectional spinal cord areas were measured in axial slices and various DTI parameters, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (lambda(parallel to)) and radial diffusivity (lambda(perpendicular to)), were calculated for the total spared white matter (WM), ventral funiculi (VF), lateral funiculi (LF) and dorsal columns (DCs) and then correlated with histopathology. Cross-sectional area measurements revealed significant atrophy (32% reduction) of the injured spinal cord at the lesion epicentre in the chronic phase of injury. Analysis of diffusion tensor parameters further showed that tissue integrity was most severely affected in the DCs, i.e. the site of immediate impact, which demonstrated a rapid and permanent decrease in FA and lambda(parallel to). In contrast, DTI parameters for the ventrolateral white matter changed more gradually with time, suggesting that these regions are undergoing more delayed degeneration in a manner that may be amenable to therapeutic intervention. Of all the DTI parameters, lambda(perpendicular to) was most closely correlated to myelin content whereas changes in FA and lambda(parallel to) appeared more indicative of axonal integrity, Wallerian degeneration and associated presence of macrophages. We conclude that longitudinal DTI at 16.4 T provides a clinically relevant, objective measure for assessing white matter pathology following contusive SCI in mice that may aid the translation of putative neuroprotective strategies into the clinic. (C) 2013 Elsevier Inc. All rights reserved.