Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions
Jannis Müller, Po‐Jui Lu, Alessandro Cagol, Esther Ruberte, Hyeong‐Geol Shin, Mario Ocampo‐Pineda, Xinjie Chen, Charidimos Tsagkas, Muhamed Baraković, Riccardo Galbusera, Matthias Weigel, Sabine Schaedelin, Yi Wang, Thanh D. Nguyen, Pascal Spincemaille, Ludwig Kappos, Jens Kühle, Jong-Ho Lee, Cristina Granziera
Abstract
BACKGROUND AND OBJECTIVES: Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals. METHODS: This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models. RESULTS: ). DISCUSSION: χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.