Characterizing white matter damage in rat spinal cord with quantitative MRI and histology.
ABSTRACT Diffusion tensor imaging (DTI) and quantitative T(2) magnetic resonance imaging (MRI) were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. Luxol Fast Blue (LFB) and myelin basic protein (MBP) staining was used to assess myelin damage, and neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining was used to assess axonal damage. Average values of myelin water fraction (MWF), fractional anisotropy (FA), longitudinal diffusivity (D(long)), transverse diffusivity (D(trans)), and average diffusivity (D(ave)) were calculated in the fasciculus gracilis, fasciculus cuneatus, and the dorsal corticospinal tract (CST) 5 mm cranial, as well as 5 and 10 mm caudal to injury and correlated with histology. These tracts were selected as these contain bundles of parallel ascending and descending axons in very circumscribed areas with little intermingling of other axonal populations. Axonal and myelin degeneration occur cranial to injury in the funiculus gracilis and caudal to injury in the CST. Both MWF and D(trans) showed significant correlation with LFB staining at 3 weeks (0.64 and -0.49, respectively) and 8 weeks post-injury (0.88 and -0.71, respectively). Both D(long) and FA correlated significantly with NF/Tub staining at 3 weeks post-injury (0.78 and 0.64, respectively), while only D(long) displayed significant correlation 8 weeks post-injury (0.58 and 0.33, respectively). This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord.
Kozlowski
Piotr
P
Departments of Radiology and Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. pkozlow@interchange.ubc.ca
Raj
Disha
D
Liu
Jie
J
Lam
Clarrie
C
Yung
Andrew C
AC
Tetzlaff
Wolfram
W
D000818:Animals; D016880:Anisotropy; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001834:Body Water / Q000502:physiology; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D008297:Male; D004676:Myelin Basic Protein / Q000032:analysis / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009434:Neural Pathways / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000032:analysis / Q000378:metabolism; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D013194:Staining and Labeling / Q000379:methods*; D013997:Time Factors; D015599:Trauma Severity Indices; D014404:Tubulin / Q000032:analysis / Q000378:metabolism; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology
D015415:Biomarkers; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D014404:Tubulin; C051774:neurofilament protein H