title: Multi-parametric quantitative MRI of normal appearing white matter in multiple sclerosis, and the effect of disease activity on T2.
abstract: White matter (WM) lesions with a distinct lesion-tissue contrast are the main radiological hallmark of multiple sclerosis (MS) in standard magnetic resonance imaging (MRI). Pathological WM changes beyond lesion development lack suitable contrasts, rendering the investigation of normal appearing WM (NAWM) more challenging. In this study, repeat quantitative MRI (qMRI) was collected in 9 relapsing remitting MS patients with mild disease over nine months. The relaxation times T1 and T2, the proton density (PD), and the magnetization transfer ratio (MTR) were analysed in the NAWM. For each parameter, both the mean value and the standard deviation were determined across large NAWM regions. The resulting 8-dimensional multi-parameter space includes parameter non-uniformities as additional descriptors of NAWM inhomogeneity. The goals of the study were to investigate (1) which of the eight parameters differ significantly between NAWM and normal WM, (2) if parameter time courses differ between patients with and without radiological disease activity, and (3) if a suitable biomarker can be derived from the multi-parameter space, allowing for NAWM characterization and differentiation from controls. On a group level, all parameters investigated except mean T1 values were significantly affected in MS NAWM. Group classification accuracy using a multi-parametric support vector machine approach in NAWM was 66.7 %. In addition, mean T2 values increased significantly with time for patients with radiological disease activity, but not for patients without radiological activity. In conclusion, our data demonstrate the potential of qMRI for investigating MS pathology in NAWM. T2 measurements in NAWM may enable monitoring of disease activity outside of overt lesions.
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany. SarahChristina.Reitz@kgu.de.|Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany. SarahChristina.Reitz@kgu.de.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Reitz
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany.|Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany.
authors.forename: Stephanie-Michelle
authors.initials: SM
authors.lastname: Hof
authors.affiliation: Department of Neurology, Johannes Gutenberg University, Mainz, Germany.|Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: MEG Unit, Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany.
authors.forename: Alla
authors.initials: A
authors.lastname: Brodski
authors.affiliation: Department of Neurology, Johannes Gutenberg University, Mainz, Germany.|Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Adriane
authors.initials: A
authors.lastname: Gröger
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany.|Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany.
authors.forename: René-Maxime
authors.initials: RM
authors.lastname: Gracien
authors.affiliation: Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Amgad
authors.initials: A
authors.lastname: Droby
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany.
authors.forename: Helmuth
authors.initials: H
authors.lastname: Steinmetz
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany.|Department of Neurology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
authors.affiliation: Department of Neurology, Johannes Gutenberg University, Mainz, Germany.|Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Deichmann
authors.affiliation: Department of Neurology, Goethe University, Frankfurt/Main, Germany.|Brain Imaging Center (BIC), Goethe University, Frankfurt/Main, Germany.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Klein
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging*; D012720:Severity of Illness Index; D060388:Support Vector Machine; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Multiple sclerosis (MS); Normal appearing white matter (NAWM); Quantitative MRI (qMRI); Relapsing remitting multiple sclerosis (RRMS)