Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation

Graham Cooper; Claudia Chien; Hanna Zimmermann; Judith Bellmann-Strobl; Klemens Ruprecht; Joseph Kuchling; Susanna Asseyer; Alexander U Brandt; Michael Scheel; Carsten Finke; Friedemann Paul

doi:10.1177/13524585211003479

Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation

Mult Scler. 2021 Dec;27(14):2180-2190. doi: 10.1177/13524585211003479. Epub 2021 Apr 15.

Authors

Affiliations

¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/ Department of Experimental Neurology and Center for Stroke Research, Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany/ Einstein Center for Neurosciences, Berlin, Germany.
² Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/ Department for Psychiatry and Psychotherapy-Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
³ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁵ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁶ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/Department of Neurology, University of California, Irvine, California, USA.
⁷ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/Department of Neuroradiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁸ Einstein Center for Neurosciences, Berlin, Germany/Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany/Einstein Center for Neurosciences, Berlin, Germany/Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Abstract

Background: Cross-sectional studies suggest normal appearing white matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting multiple sclerosis (MS).

Objective: To investigate the relationship between NAWM integrity and cortical thickness from first clinical presentation longitudinally.

Methods: NAWM integrity and cortical thickness were assessed with 3T magnetic resonance imaging (MRI) in 102 patients with clinically isolated syndrome or early MS (33.2 (20.1-60.1) years old, 68% female) from first clinical presentation over 2.8 ± 1.6 years. Fifty healthy controls (HCs) matched for age and sex were included. NAWM integrity was evaluated using the standardized T1w/T2w ratio (sT1w/T2w). The association between sT1w/T2w and cortical thickness was assessed using linear mixed models. The effect of disease activity was investigated using the No Evidence of Disease Activity (NEDA-3) criteria.

Results: At baseline, sT1w/T2w (p = 0.152) and cortical thickness (p = 0.489) did not differ from HCs. Longitudinally, decreasing sT1w/T2w was associated with cortical thickness and increasing lesion burden (marginal R² = 0.061). The association was modulated by failing NEDA-3 (marginal R² = 0.097).

Conclusion: sT1w/T2w may be a useful MRI biomarker for early MS, detecting relevant NAWM damage over time using conventional MRI scans, although with less sensitivity compared to quantitative measures.

Keywords: NEDA-3; T1w/T2w ratio; cortical thickness; longitudinal analysis; multiple sclerosis; normal appearing white matter damage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / diagnostic imaging
Cross-Sectional Studies
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis* / diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
White Matter*
Young Adult