Advanced Magnetic Resonance Imaging Biomarkers of the Injured Spinal Cord: A Comparative Study of Imaging and Histology in Human Traumatic Spinal Cord Injury

A significant problem in the diagnosis and treatment of traumatic spinal cord injury (tSCI) is the heterogeneity of secondary injury and the prediction of neurologic outcome. Imaging biomarkers specific to myelin loss and inflammation after tSCI would enable detailed assessment of the pathophysiologic processes underpinning secondary damage to the cord. Such biomarkers could be used to biologically stratify injury severity and better inform prognosis for neurologic recovery. While much work has been done to establish MRI biomarkers for SCI in animal models, the relationship between imaging findings and the underlying pathology has been difficult to discern in human tSCI due to the paucity of human spinal cord tissue. We utilized post-mortem spinal cords from individuals who suffered at tSCI to examine this relationship by performing ex vivo MRI scans before histologic analysis. We investigated the correlation between the histologic distribution of myelin loss and inflammatory cells in the injured spinal cord and a number of myelin and inflammation-sensitive MRI measures: myelin water fraction (MWF), inhomogeneous magnetisation transfer ratio (ihMTR), and diffusion tensor and diffusion kurtosis imaging-derived fractional anisotropy (FA) and axial, radial and mean diffusivity (AD, RD, MD). The histologic features were analysed by staining with Luxol Fast Blue (LFB) for myelin lipids, and Class II major histocompatibility complex (Class II MHC) and CD68 for microglia and macrophages. Both MWF and ihMTR were strongly correlated with LFB staining for myelin, supporting the use of both as biomarkers for myelin loss after SCI. A decrease in ihMTR was also correlated with the presence of Class II MHC and CD68+ immune cells in white matter. FA and RD correlated with both Class II MHC and CD68 and may therefore be useful biomarkers for inflammation after tSCI. Our work demonstrates the utility of novel MRI techniques sensitive to biological tissue damage after tSCI. This is the first step towards using these MRI techniques in the clinic to aid in decision-making.