Corpus callosum axon diameter relates to cognitive impairment in multiple sclerosis

Objective To evaluate alterations in apparent axon diameter and axon density obtained by high‐gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. Methods Thirty people with...

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Published in:Annals of clinical and translational neurology 2019-05, Vol.6 (5), p.882-892
Main Authors: Huang, Susie Y., Fan, Qiuyun, Machado, Natalya, Eloyan, Ani, Bireley, John D., Russo, Andrew W., Tobyne, Sean M., Patel, Kevin R., Brewer, Kristina, Rapaport, Sarah F., Nummenmaa, Aapo, Witzel, Thomas, Sherman, Janet C., Wald, Lawrence L., Klawiter, Eric C.
Format: Article
Language:English
Subjects:
Adult
Axons - pathology
Cognitive ability
Cognitive Dysfunction - pathology
Corpus Callosum - pathology
Diffusion Magnetic Resonance Imaging
Disability Evaluation
Estimates
Female
Histopathology
Humans
Image Processing, Computer-Assisted
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - pathology
Multiple Sclerosis, Chronic Progressive - pathology
Multiple Sclerosis, Relapsing-Remitting - pathology
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Summary:Objective To evaluate alterations in apparent axon diameter and axon density obtained by high‐gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. Methods Thirty people with MS (23 relapsing‐remitting MS [RRMS], 7 progressive MS [PMS]) and 23 healthy controls were scanned on a human 3‐tesla (3T) MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Data were fitted to a three‐compartment geometric model of white matter to estimate apparent axon diameter and axon density in the midline corpus callosum. Neurologic disability and cognitive function were measured using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Minimal Assessment of Cognitive Function in MS battery. Results Apparent axon diameter was significantly larger and axon density reduced in the normal‐appearing corpus callosum (NACC) of MS patients compared to healthy controls, with similar trends seen in PMS compared to RRMS. Larger apparent axon diameter in the NACC of MS patients correlated with greater disability as measured by the EDSS (r = 0.555, P = 0.007) and poorer performance on the Symbol Digits Modalities Test (r = ‐0.593, P = 0.008) and Brief Visuospatial Memory Test–Revised (r = −0.632, P 
ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.760