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

J Neurol. 2020 Mar;267(3):802-811. doi: 10.1007/s00415-019-09643-z. Epub 2019 Nov 25.


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.

Keywords: Atrophied T2-lesion volume; Cognition; Disease progression; MRI; Multiple sclerosis; Neurodegeneration; Optical coherence tomography; Serum neurofilament light chain.

MeSH terms

  • Adult
  • Atrophy / diagnostic imaging
  • Atrophy / pathology
  • Biomarkers / cerebrospinal fluid
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / pathology*
  • Neurofilament Proteins / cerebrospinal fluid
  • Neuroimaging
  • Prospective Studies
  • Tomography, Optical Coherence


  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L