A multimodal approach to assess the validity of atrophied T2-lesion volume as an MRI marker of disease progression in multiple sclerosis

Background: Atrophied T2-lesion volume (LV) is a novel MRI marker representing brain-lesion loss due to atrophy, able to predict long-term disability progression and conversion to secondary-progressive multiple sclerosis (MS). Objective: To better characterize atrophied T2-LV via comparison with other multidisciplinary markers of MS progression. Methods: We studied 127 MS patients (85 relapsing–remitting, RRMS and 42 progressive, PMS) and 20 clinically isolated syndrome (CIS) utilizing MRI, optical coherence tomography, and serum neurofilament light chain (sNfL) at baseline and at 5-year follow-up. Symbol Digit Modalities Test (SDMT) was obtained at follow-up. Atrophied T2-LV was calculated by combining baseline lesion masks with follow-up CSF partial-volume maps. Measures were compared between MS patients who developed or not disease progression (DP). Partial correlations between atrophied T2-LV and other biomarkers were performed, and corrected for multiple comparisons. Results: Atrophied T2-LV was the only biomarker that significantly differentiated DP from non-DP patients over the follow-up (p = 0.007). In both DP and non-DP groups, atrophied T2-LV was associated with baseline T2-LV and T1-LV (both p = 0.003), absolute change of T1-LV (DP p = 0.038; non-DP p = 0.003) and percentage of brain volume change (both p = 0.003). Furthermore, in the DP group, atrophied T2-LV was related to baseline brain parenchymal (p = 0.017) and thalamic (p = 0.003) volumes, thalamic volume change and follow-up SDMT (both p = 0.003). In non-DP patients, atrophied T2-LV was significantly related to baseline sNfL (p = 0.008), contrast-enhancing LV (p = 0.02) and percentage ventricular volume change (p = 0.003). Conclusion: Atrophied T2-LV is associated with disability accrual in MS, and to several multimodal markers of disease evolution.