Brain Advance Access originally published online on October 11, 2005
Brain 2005 128(12):2911-2925; doi:10.1093/brain/awh654
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Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis
1 NMR Research Unit, Institute of Neurology, 2 The National Hospital for Neurology and Neurosurgery, 3 Moorfields Eye Hospital and 4 Department of Neurology, Institute of Psychiatry, King's College, London, UK
Correspondence to: Kryshani T. M. Fernando, Institute of Neurology, Queen Square, London WC1N 3BG, UK E-mail: k.fernando{at}ion.ucl.ac.uk
In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12–33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.
Key Words: MTR histogram; NAWM; NAGM; multiple sclerosis; clinically isolated syndromes
Abbreviations: BPF = brain parenchymal fraction; CIS = clinically isolated syndromes; EDSS = expanded disability status scale; GMF = grey matter fraction; MTI = magnetization transfer imaging; MTR = magnetization transfer ratio; NABT = normal-appearing brain tissue; NAGM = normal-appearing grey matter; NAWM = normal-appearing white matter; NEX = number of excitations; SD = standard deviation; TE = echo time; TI = total intra-cranial volume; TR = repetition time; WMF = white matter fraction
Received May 9, 2005. Revised August 30, 2005. Accepted September 2, 2005.
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