Diffusion tensor imaging as a predictor of locomotor function after experimental spinal cord injury and recovery.
Traumatic spinal cord injury (SCI) causes long-term disability with limited functional recovery linked to the extent of axonal connectivity. Quantitative diffusion tensor imaging (DTI) of axonal integrity has been suggested as a potential biomarker for prognostic and therapeutic evaluation after trauma, but its correlation with functional outcomes has not been clearly defined. To examine this application, female Sprague-Dawley rats underwent midthoracic laminectomy followed by traumatic spinal cord contusion of differing severities or laminectomy without contusion. Locomotor scores and hindlimb kinematic data were collected for 4 weeks post-injury. Ex vivo DTI was then performed to assess axonal integrity using tractography and fractional anisotropy (FA), a numerical measure of relative white matter integrity, at the injury epicenter and at specific intervals rostral and caudal to the injury site. Immunohistochemistry for tissue sparing was also performed. Statistical correlation between imaging data and functional performance was assessed as the primary outcome. All injured animals showed some recovery of locomotor function, while hindlimb kinematics revealed graded deficits consistent with injury severity. Standard T2 magnetic resonance sequences illustrated conventional spinal cord morphology adjacent to contusions while corresponding FA maps indicated graded white matter pathology within these adjacent regions. Positive correlations between locomotor (Basso, Beattie, and Bresnahan score and gait kinematics) and imaging (FA values) parameters were also observed within these adjacent regions, most strongly within caudal segments beyond the lesion. Evaluation of axonal injury by DTI provides a mechanism for functional recovery assessment in a rodent SCI model. These findings suggest that focused DTI analysis of caudal spinal cord should be studied in human cases in relationship to motor outcome to augment outcome biomarkers for clinical cases.
1 Department of Neurosurgery, Yale University School of Medicine , New Haven, Connecticut.
Brian J
BJ
Kelley
Noam Y
NY
Harel
Chang-Yeon
CY
Kim
Xenophon
X
Papademetris
Daniel
D
Coman
Xingxing
X
Wang
Omar
O
Hasan
Adam
A
Kaufman
Ronen
R
Globinsky
Lawrence H
LH
Staib
William B J
WB
Cafferty
Fahmeed
F
Hyder
Stephen M
SM
Strittmatter
D000818:Animals; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009043:Motor Activity; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology*
diffusion tensor imaging; fractional anisotropy; kinematics; rat; spinal cord injury; tractography