Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis.

BACKGROUND Magnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS). OBJECTIVES To investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS. DESIGN Prospective study. SETTING National Hospital for Neurology and Neurosurgery and the Institute of Neurology, London, England. PATIENTS Forty-seven patients with PPMS (of whom 43 completed the study) and 18 control subjects. INTERVENTIONS Brain magnetization transfer imaging (including T2-weighted images) and volume sequences every 6 months for 3 years. MAIN OUTCOME MEASURES Changes in Expanded Disability Status Scale (EDSS) score and associations with rate of change in imaging variables. RESULTS More rapid decline in gray matter mean and peak location magnetization transfer ratio and T2 lesion load increase were associated with greater rates of progression on the EDSS. Baseline gray matter peak height magnetization transfer ratio best predicted progression over 3 years. CONCLUSION Gray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS.

[1]  Mara Cercignani,et al.  Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. , 2005, Brain : a journal of neurology.

[2]  P. Sørensen,et al.  Erratum: Remyelination is extensive in a subset of multiple sclerosis patients (Brain (2006) 129, PART 12, (3165-3172) DOI: 10.1093/brain/awl217) , 2007 .

[3]  R. Prentice Surrogate endpoints in clinical trials: definition and operational criteria. , 1989, Statistics in medicine.

[4]  P. Tofts Quantitative MRI of the Brain , 2003 .

[5]  Bruce D. Trapp,et al.  Pathogenesis of axonal and neuronal damage in multiple sclerosis , 2007, Neurology.

[6]  F. Barkhof,et al.  Long-term clinical outcome of primary progressive MS: Predictive value of clinical and MRI data , 2005, Neurology.

[7]  M. Rovaris,et al.  Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. , 2006, Brain : a journal of neurology.

[8]  F Barkhof,et al.  The role of MRI as a surrogate outcome measure in multiple sclerosis , 2002, Multiple sclerosis.

[9]  Hans Lassmann,et al.  Remyelination is extensive in a subset of multiple sclerosis patients. , 2006, Brain : a journal of neurology.

[10]  D. Paty,et al.  The natural history of primary progressive MS in British Columbia, Canada , 2005, Neurology.

[11]  B. Trapp,et al.  Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions , 2001, Annals of neurology.

[12]  G. Barker,et al.  Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences , 2006, Magnetic Resonance Materials in Physics, Biology and Medicine.

[13]  David H. Miller,et al.  Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain , 2004, Annals of neurology.

[14]  Massimo Filippi,et al.  MRI to Monitor Treatment Efficacy in Multiple Sclerosis , 2007, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[15]  M. Versavel,et al.  Can the Expanded Disability Status Scale be assessed by telephone? , 2003, Multiple sclerosis.

[16]  Hans Lassmann,et al.  Cortical demyelination and diffuse white matter injury in multiple sclerosis. , 2005, Brain : a journal of neurology.

[17]  Marco Rovaris,et al.  Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study. , 2003, Brain : a journal of neurology.

[18]  B. Brownell,et al.  The distribution of plaques in the cerebrum in multiple sclerosis , 1962, Journal of neurology, neurosurgery, and psychiatry.

[19]  J. L. Cox,et al.  Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case–control study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[20]  A J Thompson,et al.  Diagnostic criteria for primary progressive multiple sclerosis: A position paper , 2000, Annals of neurology.

[21]  Rohit Bakshi,et al.  Gray matter involvement in multiple sclerosis , 2007, Neurology.

[22]  A J Thompson,et al.  Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[23]  Z Khaleeli,et al.  Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[24]  M Rovaris,et al.  Evidence for progressive gray matter loss in patients with relapsing-remitting MS , 2005, Neurology.

[25]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[26]  A. Thompson,et al.  Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[27]  Frederik Barkhof,et al.  Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. , 2005, AJNR. American journal of neuroradiology.

[28]  P. Narayana,et al.  Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double‐blind, placebo‐controlled trial , 2007, Annals of neurology.

[29]  M. Rovaris,et al.  A new method for analyzing histograms of brain magnetization transfer ratios: comparison with existing techniques. , 2004, AJNR. American journal of neuroradiology.

[30]  A. J. Thompson,et al.  Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability , 2007, NeuroImage.

[31]  G. Ebers Natural history of primary progressive multiple sclerosis , 2004, Multiple sclerosis.

[32]  J H Simon,et al.  Brain atrophy in multiple sclerosis: what we know and would like to know , 2006, Multiple sclerosis.

[33]  Alan J. Thompson,et al.  Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis , 2004, NeuroImage.