Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

• Published in: Annals of neurology Vol. 82; no. 4; pp. 519 - 529
• Main Authors: Righart, Ruthger, Biberacher, Viola, Jonkman, Laura E., Klaver, Roel, Schmidt, Paul, Buck, Dorothea, Berthele, Achim, Kirschke, Jan S., Zimmer, Claus, Hemmer, Bernhard, Geurts, Jeroen J. G., Mühlau, Mark
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2017; John Wiley and Sons Inc
• Subjects: Aged; Aged, 80 and over; Attention; Brain; Case-Control Studies; Cerebral cortex; Cerebral Cortex - diagnostic imaging; Cohort Studies; Cortex (cingulate); Dendritic structure; Depression - diagnostic imaging; Depression - etiology; Diagnosis; Disability Evaluation; Female; Histopathology; Humans; Image Processing, Computer-Assisted; In vivo methods and tests; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Measurement methods; Middle Aged; Multiple sclerosis; Multiple Sclerosis - complications; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - pathology; Myelin; Neuroimaging; NMR; Nuclear magnetic resonance; Occipital lobe; Pathology; Patients; Resonance
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.25020

Objective
In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown.
Methods
Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors.
Results
Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin.
Interpretation
The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529