title: Tissue damage within normal appearing white matter in early multiple sclerosis: assessment by the ratio of T1- and T2-weighted MR image intensity.
abstract: Histopathological and magnetic resonance imaging (MRI) studies have shown white matter (WM) damage in early stages of multiple sclerosis (MS) beyond the apparent T2-hyperintense lesions. These changes in normal appearing WM (NAWM) are important with regard to the clinical picture and prognosis. However, the detection of changes within NAWM has so far required special imaging techniques commonly not available in clinical routine and, hence, at large scale. The purpose of this study was to detect MS-related damage of NAWM by conventional MRI. As, within NAWM, the myelin content mainly drives the T1-weighted (T1w) signal, we scaled it by the T2w signal. We tested the hypothesis that the mean T1w/T2w ratio of NAWM is decreased in MS compared to healthy controls (HC) and that it correlates with clinical measures. We developed a pipeline to determine the individual mean values of this ratio within NAWM. We studied 244 patients in early disease stages of MS (mean age 37 ± 10 years, mean disease duration 3.1 ± 2.3, Expanded Disability Status Scale 1.3 ± 1), and 78 HC (mean age 31 ± 8 years). Compared to HC, the mean T1w/T2w ratio was lowered in the patient group (P < 0.001). The difference remained significant after restricting the analysis to patients with a disease duration of 5 years or less and without disease modifying drugs. Our measures also correlated with clinical scores. We believe that the mean T1w/T2w ratio is a promising candidate to assess MS-related tissue damage within NAWM at large scale.
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|TUM-Neuroimaging Center, Technische Universität München, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Beer
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|TUM-Neuroimaging Center, Technische Universität München, Munich, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Biberacher
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|TUM-Neuroimaging Center, Technische Universität München, Munich, Germany.|Department of Statistics, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|TUM-Neuroimaging Center, Technische Universität München, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Righart
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Buck
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Berthele
authors.affiliation: Department of Neuroradiology, Technische Universität München, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kirschke
authors.affiliation: TUM-Neuroimaging Center, Technische Universität München, Munich, Germany.|Department of Neuroradiology, Technische Universität München, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Zimmer
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.|Munich Cluster for Systems Neurology, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany. mark.muehlau@tum.de.|TUM-Neuroimaging Center, Technische Universität München, Munich, Germany. mark.muehlau@tum.de.|Munich Cluster for Systems Neurology, Munich, Germany. mark.muehlau@tum.de.
authors.forename: M
authors.initials: M
authors.lastname: Mühlau
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging*; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Clinically isolated syndrome; Magnetic resonance imaging; Multiple sclerosis; Normal appearing white matter; T1-weighted/T2-weighted ratio