title: An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis.
abstract: In established multiple sclerosis, tissue abnormality-as assessed using magnetization transfer ratio-increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1-5 mm and 6-10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1-5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus -0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T2lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T2lesions (P = 0.918), periventricular T2lesions (P = 0.580) or gadolinium-enhancing T1lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation.
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.|Department of Clinical Neurosciences, University of Cambridge, Box 165, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: J William L
authors.initials: JW
authors.lastname: Brown
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.|Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pardini
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Wallace J
authors.initials: WJ
authors.lastname: Brownlee
authors.affiliation: Department of Neurology, Royal Free Hospital, Pond Street, London, UK.
authors.forename: Kryshani
authors.initials: K
authors.lastname: Fernando
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Samson
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.|Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, UK.|National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK.
authors.forename: Ferran
authors.initials: F
authors.lastname: Prados Carrasco
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, UK.|National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK.|Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.|Brain MRI 3T Center, C. Mondino National Neurological Institute, Pavia, Italy.|Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Gandini Wheeler-Kingshott
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.|National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK d.chard@ucl.ac.uk.|National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK.
authors.forename: Declan T
authors.initials: DT
authors.lastname: Chard
mesh_terms: D000328:Adult; D001284:Atrophy; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging*; D009902:Optic Neuritis / Q000000981:diagnostic imaging / Q000209:etiology; D011522:Protons; D066127:White Matter / Q000473:pathology; D055815:Young Adult
chemical_list: D011522:Protons
keywords: magnetization transfer ratio; multiple sclerosis; normal-appearing white matter