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Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study

Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

Correspondence to:
Correspondence to:
Professor Alan Thompson
Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; a.thompson{at}ion.ucl.ac.uk

Background: Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pathological processes occurring in normal appearing brain tissue (NABT) involving both white matter (NAWM) and grey matter (NAGM). Magnetisation transfer imaging (MTI) is capable of identifying these processes and may be particularly informative when applied to patients with early PPMS.

Aim: To assess the relationship between abnormalities in NABT identified by MTI and disability and other radiological data in patients with early PPMS.

Methods: We studied 43 patients within 5 years of disease onset and 43 controls. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) were scored. Magnetisation transfer ratios (MTR) of NABT, NAWM, and NAGM were calculated and the following MTR parameters were measured: mean, peak height, peak location, and MTR value at the 25th, 50th, and 75th percentiles. Proton density, T2, T1, and gadolinium enhancing lesion loads were also calculated.

Results: Differences were found between patients and controls in mean, peak height, and peak location of NAWM and NAGM (p0.001). Weak to moderate correlations were found between MTR parameters and disability in both NAWM and NAGM. Strong correlations between MTR parameters and lesion loads were found, particularly in NAWM.

Conclusion: MTR abnormalities are seen in NAWM and NAGM in early PPMS and both are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.

Abbreviations: COVs, coefficients of variation; DSS, Disability Status Score; EDSS, Expanded Disability Status Scale; FOV, field of view; FSE, fast spin echo; Gd, gadolinium; GM, grey matter; M, mean MTR; MRI, magnetic resonance imaging; MS, multiple sclerosis; MSFC, Multiple Sclerosis Functional Composite; MTI, magnetisation transfer imaging; MTR, magnetisation transfer ratio; NABT, normal appearing brain tissue; NAGM, normal appearing grey matter; NAWM, normal appearing white matter; NEX, number of excitations; P25, MTR value of the 25th percentile; P50, MTR value of the 50th percentile; P75, MTR value of the 75th percentile; PD, proton density; PH, peak height; PL, peak location; PPMS, primary progressive multiple sclerosis; pu, percent unit; RRMS, relapsing-remitting multiple sclerosis; SE, spin echo; TE, echo time; TR, repetition time; WB, whole brain; WM, white matter

Keywords: early stage; magnetisation transfer imaging; normal appearing grey matter; normal appearing white matter; primary progressive multiple sclerosis

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