Evolution of Magnetic Resonance Imaging as Predictors and Correlates of Functional Outcome after Spinal Cord Contusion Injury in the Rat

Abstract
Clinical methods for determining the severity of traumatic spinal cord injury (SCI) and long-term functional outcome in the acute setting are limited in their prognostic accuracy because of the heterogeneity of injury and dynamic injury progression. The aim of this study was to evaluate the time course and sensitivity of advanced magnetic resonance imaging (MRI) methods to neurological function after SCI in a rat contusion model. Rats received a graded contusion injury at T10 using a weight-drop apparatus. MRI consisted of morphological measures from T2-weighted imaging, quantitative T2 imaging, and diffusion-weighted imaging (DWI) at 1, 30, and 90 days post-injury (dpi). The derived metrics were compared with neurological function assessed using weekly Basso, Beattie, and Bresnahan (BBB) locomotor scoring and return of reflexive micturition function. At the acute time point (1 dpi), diffusion metrics sensitive to axonal injury at the injury epicenter had the strongest correlation with time-matched BBB scores and best predicted 90-dpi BBB scores. At 30 dpi, axonal water fraction derived from DWI and T2 values were both correlated with time-matched locomotor scores. At the chronic time point (90 dpi), cross-sectional area was most closely correlated to BBB. Overall, the results demonstrate differential sensitivity of MRI metrics at different time points after injury, but the metrics follow the expected pathology of acute axonal injury followed by continued degeneration and finally a terminal level of atrophy. Specificity of DWI in the acute setting may make it impactful as a prognostic tool while T2 imaging provided the most information about injury severity in chronic injury.