Noninvasive Quantification of Axonal Loss in the Presence of Tissue Swelling in Traumatic Spinal Cord Injury Mice

Neuroimaging plays an important role in assessing axonal pathology after traumatic spinal cord injury. However, coexisting inflammation confounds imaging assessment of the severity of axonal injury. Herein, we applied diffusion basis spectrum imaging (DBSI) to quantitatively differentiate and quantify underlying pathologies in traumatic spinal cord injury at 3 days post-injury. Results reveal that DBSI was capable of detecting and differentiating axonal injury, demyelination, and inflammation-associated edema and cell infiltration in contusion-injured spinal cords. DBSI was able to detect and quantify axonal loss in the presence of white matter tract swelling. The DBSI-defined apparent axonal volume correlated with the corresponding histological markers. DBSI-derived pathological metrics could serve as neuroimaging biomarkers to differentiate and quantify coexisting white matter pathologies in spinal cord injury, providing potential surrogate outcome measures to assess spinal cord injury progression and response to therapies.