No abstract

This study shows that diffusion-weighted imaging is able to identify MS lesions with severe tissue disruption. It also shows that widespread increased diffusion can be measured in the NAWM from patients with MS, and suggests that such changes are, at least partially, independent of larger abnormalities.

Objective During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so‐called “brain‐age” paradigm. Here, we evaluated whether brain‐predicted age difference (brain‐PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. Methods In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow‐up time: patients 3.41 years, healthy controls 1.97 years), we measured “brain‐predicted age” using T1‐weighted MRI. We compared brain‐PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain‐PAD and Expanded Disability Status Scale (EDSS) were explored. Results Patients with MS had markedly higher brain‐PAD than healthy controls (mean brain‐PAD +10.3 years; 95% confidence interval [CI] = 8.5–12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain‐PADs were in secondary‐progressive MS (+13.3 years; 95% CI = 11.3–15.3). Brain‐PAD at study entry predicted time‐to‐disability progression (hazard ratio 1.02; 95% CI = 1.01–1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain‐PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). Interpretation The brain‐age paradigm is sensitive to MS‐related atrophy and clinical progression. A higher brain‐PAD at baseline was associated with more rapid disability progression and the rate of change in brain‐PAD related to worsening disability. Potentially, “brain‐age” could be used as a prognostic biomarker in early‐stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93–105

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.