10.25376/hra.8206598.v1
Susie Y. Huang
Susie Y.
Huang
Qiuyun Fan
Qiuyun
Fan
Natalya Machado
Natalya
Machado
Ani Eloyan
Ani
Eloyan
John Bireley
John
Bireley
Andrew Russo
Andrew
Russo
Sean Tobyne
Sean
Tobyne
Kevin Patel
Kevin
Patel
Kristina Brewer
Kristina
Brewer
Sarah Rapaport
Sarah
Rapaport
Aapo Nummenmaa
Aapo
Nummenmaa
Thomas Witzel
Thomas
Witzel
Janet Sherman
Janet
Sherman
Lawrence L. Wald
Lawrence
L. Wald
Eric Klawiter
Eric
Klawiter
Corpus callosum axon diameter relates to cognitive impairment in multiple sclerosis
Health Research Alliance
2019
Diffusion MRI
Multiple Sclerosis
axon diameter
Neurology and Neuromuscular Diseases
2019-05-30 21:22:45
Journal contribution
https://hra.figshare.com/articles/journal_contribution/Corpus_callosum_axon_diameter_relates_to_cognitive_impairment_in_multiple_sclerosis/8206598
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 < 0.01), tests of interhemispheric processing speed and new learning and memory, respectively. Interpretation: Apparent axon diameter in the corpus callosum obtained from high-gradient diffusion MRI is a potential imaging biomarker that may be used to understand the development and progression of cognitive impairment in MS.