7T MRI Differentiates Remyelinated from Demyelinated Multiple Sclerosis Lesions

Abstract

Objective: To noninvasively assess myelin status in chronic white matter lesions of multiple sclerosis (MS), we developed and evaluated a simple classification scheme based on T1 relaxation time maps derived from 7-tesla postmortem and in vivo MRI. Methods: Using the MP2RAGE MRI sequence, we classified 36 lesions from 4 postmortem MS brains as "long-T1," "short-T1," and "mixed-T1" by visual comparison to neocortex. Within these groups, we compared T1 times to histologically derived measures of myelin and axons. We performed similar analysis of 235 chronic lesions with known date of onset in 25 MS cases in vivo and in a validation cohort of 222 lesions from 66 MS cases, investigating associations with clinical and radiological outcomes. Results: Postmortem, lesions classified qualitatively as long-T1, short-T1, and mixed-T1 corresponded to fully demyelinated, fully remyelinated, and mixed demyelinated/remyelinated lesions, respectively (p ≤ 0.001). Demyelination (rather than axon loss) dominantly contributed to initial T1 prolongation. We observed lesions with similar characteristics in vivo, allowing manual classification with substantial interrater and excellent intrarater reliability. Short-T1 lesions were most common in the deep white matter, whereas long-T1 and mixed-T1 lesions were prevalent in the juxtacortical and periventricular white matter (p = 0.02) and were much more likely to have paramagnetic rims suggesting chronic inflammation (p < 0.001). Older age at the time of lesion formation portended less remyelination (p = 0.007). Interpretation: 7-tesla T1 mapping with MP2RAGE, a clinically available MRI method, allows qualitative and quantitative classification of chronic MS lesions according to myelin content, rendering straightforward the tracking of lesional myelination changes over time.

Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression

“…Of note, in the multivariate analysis, beside the baseline EDSS score, the proportion of SELs among WM lesions and the baseline MTR of SELs were retained as the only independent predictors of EDSS score worsening, whereas only the baseline MTR of SELs independently predicted SPMS conversion. Accordingly, the presence of a higher proportion of SELs among WM lesions may identify patients with RRMS with a substantially higher amount of chronic compartmentalized inflammation that is likely to represent one of the most relevant pathologic processes significantly contributing to disability progression in MS. 29 Of note, our results are also consistent with previous studies that identified chronic active lesions on susceptibility-based imaging and showed that the presence of iron rim lesions was associated with a more aggressive disease course, 10 neurodegenerative phenomena, 10,14,15,30 and EDSS score progression over a shorter follow-up. 12,13 The idea to merge T1-weighted and T2-weighted sequences was related to be consistent with the methodology already applied and implemented in the original study that proposed the method in a very large data set.…”

“…Of interest, lower baseline MTR values of SELs were also associated with a higher risk of EDSS score worsening. Previous studies have suggested that compared with non-SELs or inactive lesions, SELs and chronic active lesions are more destructive, and their microstructural abnormalities, reflecting severe demyelination and axonal loss, 6,15,19,20,30 may contribute to irreversible disability. [11][12][13]16,17 Differently from previous studies, 16,17 Moreover, although T 1 signal intensity was calculated from T 1 -weighted images that were rescaled and normalized using longitudinal data of each patient, a more accurate and reliable quantification of T 1 signal intensity should be performed using T 1 relaxation mapping that was not available in our study.…”

Replenishing the Aged Brains: Targeting Oligodendrocytes and Myelination?

“…Advances in neuroimaging contributes to explore macroscopical and microstructural changes in white matter ( Ding et al, 2021 ; Kolb et al, 2021 ). Taking advantage of MRI imaging and diffusion tensor imaging (DTI), a variety of age-related white matter changes, including reduced white matter volume, white matter lesions, disrupted white matter integrity, and subsequent cortical disconnection have all been observed in normal aging brains ( Caligiuri et al, 2015 ).…”

MRI Prognostic Factors in Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, and Myelin Oligodendrocyte Antibody Disease

“…A straightforward approach to evaluate mechanisms of tissue repair and remyelination in chronic MS lesions has been recently proposed. Interestingly, the combination of a qualitative classification of lesions on MP2RAGE T1 maps with susceptibility-based 7T MRI seems to classify chronic lesions according to myelin content and to identify patients with a high risk for worse outcomes ( 129 ).…”