Objective To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS).
Methods 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm3) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured.
Results Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces.
Conclusions In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation.
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Contributors MP took part in study concept and design, analysis and interpretation of data, drafting of manuscript and statistical analysis. CHS, FP, ÖYi and SHvdP wre involved in analysis and interpretation of data and critical revision of manuscript.
VS took part in acquisition of data, analysis and interpretation of data and critical revision of manuscript. NM was involved in acquisition of data and critical revision of manuscript. RSS took part in analysis and interpretation of data, critical revision of manuscript and technical support. MJC and SO were involved in interpretation of data, critical revision of manuscript and study supervision. CAMGW-K took part in MRI protocol setup, critical revision of manuscript, technical support and study supervision. DHM took part in study concept and design, interpretation of data, critical revision of manuscript and study supervision. DTC was involved in study concept and design, analysis and interpretation of data, critical revision of manuscript and study supervision.
Funding NMR Research Unit is supported by the Multiple Sclerosis Society in the UK and the UCL UCLH Comprehensive Biomedical Research Centre. FP is funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative). SO is funded by the Engineering and Physical Sciences Research Council (EP/H046410/1, EP/J020990/1, EP/K005278), the Medical Research Council (MR/J01107X/1), the EU-FP7 project VPH-DARE@IT (FP7- ICT-2011-9-601055), and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative BW.mn.BRC10269). DC has received research support from the MS Society of Great Britain and Northern Ireland, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.
Competing interests MP received research support from Novartis. CHS reports no disclosure. FP reports no disclosures. ÖY has received lecture fees from Teva, Novartis and Bayer Schering which was exclusively used for funding of research and continuous medical education in the Department of Neurology at the University Hospital Basel. VS receives research support from Biogen Idec and Novartis. NMt reports no disclosures. RSS reports no disclosures. SvdP reports no disclosures. MJC reports no disclosures. SO reports no disclosures. CAMGW-K is on the advisory board for BG12 (Biogen). DHM has received honoraria from Biogen Idec, Novartis, GlaxoSmithKline, and Bayer Schering, and research grant support for doing MRI analysis in multiple sclerosis trials sponsored by GlaxoSmithKline, Biogen Idec, and Novartis. DTC has received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss MS Society, Excemed (previously Serono Symposia International Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for advisory board work; meeting expenses from Merck, Teva, Novartis, the MS Trust and National MS Society; and has previously held stock in GlaxoSmithKline.
Patient consent Obtained.
Ethics approval NRES Committee London-Queen Square.
Provenance and peer review Not commissioned; externally peer reviewed.
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