Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

Abstract

Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that axial diffusivity (ljj), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL=6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n ¼ 8 for each group). In-vivo DTI examinations were performed immediately after SCI. Longitudinal measurements of hindlimb locomotor recovery were obtained using the Basso mouse scale (BMS). Injured and spared regions of ventrolateral white matter (VLWM) were reliably separated in the hyperacute phase by threshold segmentation. Measurements of ljj were compared with histology in the hyperacute phase and 14 days after injury. The spared normal VLWM determined by hyperacute ljj and 14-day histology correlated well (r ¼ 0.95). A strong correlation between hindlimb locomotor function recovery and ljj-determined spared normal VLWM was also observed. The odds of significant locomotor recovery increased by 18% with each 1% increase in normal VLWM measured in the hyperacute phase (odds ratio ¼ 1.18, p ¼ 0.037). The capability of measuring subclinical changes in spinal cord physiology and murine genetic advantages offer an early window into the basic mechanisms of SCI that was not previously possible. Although significant obstacles must still be overcome to derive similar data in human patients, the path to clinical translation is foreseeable and achievable.

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

“…Whereas changes in diffusivity related to Wallerian degeneration has been a focus of DTI studies after injury, GM diffusion changes suggest that the entire spinal cord is involved. 23,[43][44][45] A limited number of studies have reported diffusion characteristics from GM regions, and it is thought that some of these changes occur because of astrocytic activity in GM triggered by Wallerian degeneration in WM. 28,38,46 The similarity of changes in diffusion of both GM and WM is also consistent with a generalized change in water balance throughout the spinal cord.…”

Chronic Cervical Spinal Cord Injury: DTI Correlates with Clinical and Electrophysiological Measures

“…Recent developments in MR pulse sequence design have greatly reduced these problems (Thurnher and Law 2009;Wilm, Gamper et al 2009;Wilm, Svensson et al 2007). Clinical findings correlate with DTI metrics of the injured spinal cord (Budzik, Balbi et al 2011;Chang, Jung et al 2010;Kim, Loy et al 2010;Qian, Chan et al 2011). Few studies have explored the relationship between structural integrity, evaluated using DTI, and physiological function of the human spinal cord Kerkovsky, Bednarik et al 2011;Qian, Chan et al 2011).…”

Magnetic resonance microimaging of the spinal cord in the SOD1 mouse model of amyotrophic lateral sclerosis detects motor nerve root degeneration

“…In the experimental allergic encephalomyelitis model of multiple sclerosis, contrast changes have been observed in conventional anatomic images (Schellenberg et al, 2007), axial diffusivity has been correlated with axonal damage (Budde et al, 2008;Budde et al, 2007;Budde et al, 2009), and decreased quantitative T2 and magnetic transfer values have been shown (McCreary et al, 2009). Numerous studies have also assessed white matter integrity in mouse models of spinal cord injury, using diffusion tensor imaging Kim et al, 2010;Loy et al, 2007;Tu et al, 2010), T1-and T2-weighted imaging (Gonzalez-Lara et al, 2009;Levene et al, 2008;Nishi et al, 2007), and MRM (Bilgen, 2007). In mouse models of ALS, MRM has been used to show a decrease in total white matter volume of the spinal cord (Petrik et al, 2007) …”