Abstract
Remote neurodegenerative changes in supraspinal white matter (WM) can manifest after central lesions such as spinal cord injury (SCI). The majority of diffusion tensor imaging (DTI) studies use traditional metrics such as fractional anisotropy (FA) and mean diffusivity (MD) to investigate microstructural changes in cerebral WM after SCI. However, interpretation of FA readouts is often challenged by inherent limitations of the tensor model. Recent developments in novel diffusion markers, such as fiber density (FD), allows more accurate depictions of WM pathways and has shown more reliable quantification of WM alterations compared to FA in recent studies of neurological diseases. This study investigated if FD provides useful characterization of supraspinal WM integrity after SCI in addition to the traditional DTI readouts. FA, MD, and FD maps were derived from diffusion datasets of 20 patients with chronic SCI and compared with 19 healthy controls (HC). Group differences were investigated across whole brain WM using tract-based spatial statistics and averaged diffusion values of the corticospinal tract (CST) and thalamic radiation (TR) were extracted for comparisons between HC and SCI subgroups. We also related diffusion readouts of the CST and TR with clinical scores of sensorimotor function. To investigate which diffusion markers of the CST and TR delineate HC and patients with SCI a receiver operating characteristic (ROC) analysis was performed. Overall, patients with an SCI showed decreased FA of the TR and CST. ROC analysis differentiated HC and SCI based on diffusion markers of large WM tracts including FD of the TR. Furthermore, patients' motor function was positively correlated with greater microstructural integrity of the CST. While FD showed the strongest correlation, motor function was also associated with FA and MD of the CST. In summary, microstructural changes of supraspinal WM in patients with SCI can be detected using FD as a complementary marker to traditional DTI readouts and correlates with their clinical characteristics. Future DTI studies may benefit from utilizing this novel marker to investigate complex large WM tracts in patient cohorts with varying presentations of SCI or neurodegenerative diseases.
Highlights
Spinal cord injury (SCI) characteristically results in impairment of the central nervous system and presents with varying clinical characteristics, e.g., loss of motor and sensory function due to disruption of efferent and afferent pathways [1, 2]
This study explored whether FD, a novel diffusion marker, provides useful characterization of microstructural alterations of cerebral white matter (WM) in patients with SCI
No group differences were observed with FD, FD correlates slightly stronger to the clinical outcome of SCI patients as compared to fractional anisotropy (FA) and mean diffusivity (MD), which could prove valuable in investigating complex WM pathways such as those involved with sensorimotor processing
Summary
Spinal cord injury (SCI) characteristically results in impairment of the central nervous system and presents with varying clinical characteristics, e.g., loss of motor and sensory function due to disruption of efferent and afferent pathways [1, 2]. Current diffusion tensor imaging (DTI) studies have reported microstructural changes within the cerebellum, brainstem regions and large WM tracts [8,9,10,11,12,13,14]. These DTI studies have provided insight on the impact of SCI in brain WM integrity, e.g., neurodegeneration, as indirectly measured and inferred by fractional anisotropy (FA) and mean diffusivity (MD), respectively [15,16,17,18]. Studies that investigated correlations between clinical characteristics and WM integrity reported that SCI patients with better sensory and motor function showed higher FA values of the posterior thalamic radiations (TR) [13] and pathways of the CST [10], respectively
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