Longitudinal Comparison of Two Severities of Unilateral Cervical Spinal Cord Injury Using Magnetic Resonance Imaging in Rats

Abstract

Magnetic resonance imaging (MRI) should be a powerful tool for characterization of spinal cord pathology in animal models. We evaluated the utility of medium-field MRI for the longitudinal assessment of progression of spinal cord injury (SCI) in a rat model. Thirteen adult rats were subjected to a 6.25 or 25 g-cm unilateral cervical SCI, and underwent MRI and behavioral tests during a 3-week study period. MRI was also performed post-mortem. Quantification of cord swelling, hypointense and hyperintense signal, and lesion length were the most valuable parameters to determine and were highly correlated to behavioral and histopathological measures. Immediately after injury, MRI showed loss of gray matter-white matter differentiation, presence of scattered hyperintense signal and local hypointense signal, and cord swelling in both groups. At 7 days after injury, the spinal cord in the 25 g-cm group was significantly larger than that of the 6.25 g-cm group (p = 0.02). Contrast enhancement of the lesion was seen at 24 h in the 6.25 g-cm group, and at 24 h and 7 days in the 25 g-cm group. The volume of hypointense signal, representing hemorrhage, throughout the lesion region was significantly larger in the 25 g-cm compared to the 6.25 g-cm group at both 14 and 21 days after SCI (p, </= 0.04). The appearance of the scattered hyperintense signal, initially representing edema, at later time points changed to a rim of hyperintense signal surrounding the lesion cavity. Significant correlations were found between cord swelling at 7 days after SCI, and lesion length and gray and white matter sparing as determined by histopathology. Other parameters that were highly correlated with histopathology were quantity of hyperintense and hypointense signal, and in vivo lesion length. Hypointense signal and in vivo lesion length were highly correlated to behavior. Significant correlation was also found between parameters determined by MRI: swelling, hypointense signal, hyperintense signal, and lesion length. MRI is a valuable imaging modality to assess the temporal evolution of SCI and to distinguish different severities of cervical SCI in rats. In future, MRI could be applied as a screening tool to either administer goal-directed therapies, or enable even group distribution, prior to therapeutic intervention for example through quantification and matching of swelling and edema.