TI-relaxation time changes over five years in relapsing-remitting multiple sclerosis

The pathological effects of multiple sclerosis are not confined to lesions; tissues that appear normal on conventional magnetic resonance imaging scans are also affected, albeit subtly. One imaging technique that has proven sensitive to such effects is T1-relaxation time measurement, with previous work demonstrating abnormalities in normal-appearing white matter and grey matter. In this work we investigated the evolution of T1-relaxation time changes in normal-appearing white matter and grey matter in relapsing—remitting multiple sclerosis. Three- and five-year follow-up data from 35 people with clinically early (a mean of 1.6 years from first clinical event) relapsing—remitting multiple sclerosis and 15 healthy controls were analysed. T1-relaxation time histograms were extracted from normal-appearing white matter and grey matter, and mean, peak height and peak location values were estimated. T1-relaxation time peak height declined in the multiple sclerosis normal-appearing white matter and grey matter, but not the control group (rate difference p = 0.024 in normal-appearing white matter, in normal-appearing grey matter p = 0.038); other T1-relaxation time changes were not significantly different between groups. Changes in T1-relaxation time measures did not correlate with increases in brain T2-weighted lesion loads or Expanded Disability Status Scale scores. These results suggest that the processes underlying changes in normal-appearing white matter and grey matter T1-relaxation times are not immediately linked to white matter lesion formation, and may represent more diffuse but progressive sub-clinical pathology in relapsing—remitting multiple sclerosis.

[1]  A J Thompson,et al.  Normal-appearing grey and white matter T1 abnormality in early relapsing–remitting multiple sclerosis: a longitudinal study , 2007, Multiple sclerosis.

[2]  Lublin Fd,et al.  Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. , 1996 .

[3]  À. Rovira,et al.  Baseline MRI predicts future attacks and disability in clinically isolated syndromes , 2006, Neurology.

[4]  P M Matthews,et al.  MRI Brain T1 Relaxation Time Changes in MS Patients Increase Over Time in Both the White Matter and the Cortex , 2003, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[5]  D. N. Landon,et al.  Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[6]  S. Rombouts,et al.  Voxel-based analysis of quantitative T1 maps demonstrates that multiple sclerosis acts throughout the normal-appearing white matter. , 2006, AJNR. American journal of neuroradiology.

[7]  Al Ozonoff,et al.  Relaxo-volumetric multispectral quantitative magnetic resonance imaging of the brain over the human lifespan: global and regional aging patterns. , 2009, Magnetic resonance imaging.

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

[9]  G. Comi,et al.  A 3-year diffusion tensor MRI study of grey matter damage progression during the earliest clinical stage of MS , 2008, Journal of Neurology.

[10]  Hans Lassmann,et al.  Widespread Demyelination in the Cerebellar Cortex in Multiple Sclerosis , 2007, Brain pathology.

[11]  David H. Miller,et al.  Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain , 2007, Journal of magnetic resonance imaging : JMRI.

[12]  F. Barkhof.  The clinico‐radiological paradox in multiple sclerosis revisited , 2002, Current opinion in neurology.

[13]  G. Barker,et al.  Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques. , 1996, Magnetic resonance imaging.

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

[15]  A. J. Thompson,et al.  Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis , 2005, Journal of Neurology.

[16]  T. Kilpatrick,et al.  Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses , 2006, Journal of Clinical Neuroscience.

[17]  A. Thompson,et al.  Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. , 2008, Brain : a journal of neurology.

[18]  Massimo Filippi,et al.  Normal-appearing white and grey matter damage in MS , 2007, Journal of Neurology.

[19]  M Cercignani,et al.  Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[20]  David H. Miller,et al.  Normal-appearing brain t1 relaxation time predicts disability in early primary progressive multiple sclerosis. , 2007, Archives of neurology.

[21]  F. Barkhof,et al.  Whole-brain T1 mapping in multiple sclerosis: global changes of normal-appearing gray and white matter. , 2006, Radiology.

[22]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[23]  A. Thompson,et al.  T1 histograms of normal-appearing brain tissue are abnormal in early relapsing-remitting multiple sclerosis , 2002, Multiple Sclerosis.

[24]  C. Polman,et al.  Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. , 2004, Archives of neurology.

[25]  M. Brodsky,et al.  Neurologic impairment 10 years after optic neuritis. , 2004, Archives of neurology.

[26]  C. Tanaka,et al.  Proton nuclear magnetic resonance studies on brain edema. , 1982, Journal of neurosurgery.

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

[28]  M. Filippi,et al.  MRI evidence for multiple sclerosis as a diffuse disease of the central nervous system , 2005, Journal of Neurology.

[29]  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.

[30]  G. Barker,et al.  Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[31]  G J Parker,et al.  Accurate multislice gradient echo T1 measurement in the presence of non‐ideal RF pulse shape and RF field nonuniformity , 2001, Magnetic resonance in medicine.

[32]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[33]  Frederik Barkhof,et al.  Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. , 2005, Radiology.

[34]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.