Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study.
Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing-remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls (p values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score (ρ = -0.39, p = 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score (p values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics.
Medical Degree Program, New York University School of Medicine, New York, NY, USA.
Ivan
I
de Kouchkovsky
Department of Radiology, Neurology (J.H.), New York University School of Medicine, New York, NY, USA.
Els
E
Fieremans
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lazar
L
Fleysher
Department of Neurology, New York University School of Medicine, New York, NY, USA.
Joseph
J
Herbert
Department of Radiology, Neurology (J.H.), New York University School of Medicine, New York, NY, USA.
Robert I
RI
Grossman
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. matilde.inglese@mssm.edu.|Department of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. matilde.inglese@mssm.edu.|Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova and IRCCS AOU San Martino-IST, Genoa, Italy. matilde.inglese@mssm.edu.
Matilde
M
Inglese
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D017281:Cost of Illness; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D015233:Models, Statistical; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009434:Neural Pathways / Q000000981:diagnostic imaging; D011446:Prospective Studies; D012372:ROC Curve; D066127:White Matter / Q000000981:diagnostic imaging*
DKI; DTI; EDSS; MRI; Multiple sclerosis