Abstract
This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.
Highlights
Traumatic injuries to spinal cord (SCI) may impair sensory, motor and/or autonomic functions and compromise the quality of life[1]
We report our measurements of diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) from regions of interest (ROIs) in different tracts and locations, and compared the DTI parameters (1) between segments above and below the injury in the damaged dorsal column tract, (2) between dorsal column tracts on the injured versus the non-injured side, (3) between dorsal and lateral tracts on the injured side, (4) between dorsal and lateral tracts on the non-injured side, (5) across time to see which parameters change after injury, and (6) between pre-lesion and post-lesion conditions within the spinal cord
The injury site was located in the right dorsal column tract as planned, and showed reduced FA but increased MD, AD and RD values
Summary
Traumatic injuries to spinal cord (SCI) may impair sensory, motor and/or autonomic functions and compromise the quality of life[1]. Progress in developing effective therapies has been hindered partly by our inability to track and quantify injury associated pathological changes in different tracts of the cord, or to differentiate axon disruption and demyelination within the cord over time, in a segment and tract-specific manner. This inability reflects the poor sensitivity, specificity and spatial resolution of the imaging methods available. In particular we evaluated the relationships between changes in quantitative diffusion metrics within specific sensory (dorsal column) and motor (lateral column) white matter tracts after a well-localized, targeted injury, along with corresponding behavioral deficits in sensorimotor function and skilled hand uses in primates. A major scientific objective is to determine the degree to which the recovery of hand sensorimotor impairment is linked to the recovery of fiber disruption and demyelination of the dorsal column tract white matter that is known to carry fine touch information to the brain and influence motor controls
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