Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis.
BACKGROUND
Spinal cord (SC) pathology is a major contributor to clinical disability in multiple sclerosis (MS). Conventional magnetic resonance imaging (MRI), specifically SC-MRI lesion load measures that include lesion count and volume, demonstrate only a modest relationship with the clinical status of MS patients. Although SC cross-sectional area (CSA) correlates better with clinical dysfunction than MRI lesion count, SC atrophy likely signifies irreversible tissue loss. Using quantitative MRI indices sensitive to early and late microstructural changes in the spinal cord, we searched for the presence of better correlations between MRI measures and clinical status in MS.


OBJECTIVE
We investigated whether diffusion-tensor imaging indices and the magnetization-transfer ratio (MTR) were better associated with the clinical status of MS patients than conventional SC-MRI measures.


METHODS
A total of 129 MS patients underwent 3-tesla cervical SC-MRI and quantitative sensorimotor function testing, using the Vibratron-II and dynamometer. Regions-of-interest circumscribed the SC on axial slices between C3-C4. We calculated SC-CSA, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (λ perpendicular), parallel diffusivity (λ||) and MTR. We used multivariable linear regression to determine if there were any associations between MRI indices and clinical measures of dysfunction.


RESULTS
All MRI indices were significantly different in subjects with MS versus healthy controls, and between the progressive versus relapsing MS subtypes, with the exception of λ||. In multivariable regression models that were adjusted for age, sex, brain parenchymal fraction, and SC-CSA, the MRI indices independently explained variability in hip flexion strength (p-values: MD, λ perpendicular, λ|| < 0.001; FA = 0.07), vibration sensation threshold (p-values: FA = 0.04; MTR = 0.05; λ perpendicular = 0.06), and Expanded Disability Status Scale scores (p-values: FA = 0.003; MD = 0.03; λ perpendicular = 0.005; MTR = 0.02).


CONCLUSIONS
In a large, heterogeneous MS sample, quantitative SC-MRI indices demonstrated independent associations with system-specific and global clinical dysfunction. Our findings suggest that the indices studied may provide important information about microstructural SC changes and the substrates of limb disability in MS. The identified structure-function relationships underpin the potential utility of these measures in assessments of therapeutic efficacy.
Department of Neurology, Johns Hopkins University, 600 N Wolfe Street, Pathology 627, Baltimore, MD 21287, USA. joh20@jhmi.edu
Jiwon
J
Oh
Kathleen
K
Zackowski
Min
M
Chen
Scott
S
Newsome
Shiv
S
Saidha
Seth A
SA
Smith
Marie
M
Diener-West
Jerry
J
Prince
Craig K
CK
Jones
Peter C M
PC
Van Zijl
Peter A
PA
Calabresi
Daniel S
DS
Reich
D000328:Adult; D001921:Brain / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*