Normal-appearing grey and white matter T1 abnormality in early relapsing–remitting multiple sclerosis: a longitudinal study

Objective To investigate the presence and evolution of T1 relaxation time abnormalities in normal-appearing white matter (NAWM) and grey matter (GM), early in the course of relapsing–remitting multiple sclerosis (MS). Methods Twenty-three patients with early relapsing–remitting MS and 14 healthy controls were imaged six monthly for up to three years. Mean follow-up was 26 months for MS patients and 24 months for controls. Dual-echo fast-spin echo and gradient-echo proton-density and T1-weighted data sets (permitting the calculation of a T1 map) were acquired in all subjects. GM and NAWM T1 histograms were produced and a hierarchical regression model was used to investigate changes in T1 over time. Results At baseline, significant patient-control differences were seen, both in NAWM (P = 0.001) and in GM (P = 0.01). At follow-up, there was no evidence for a serial change in either mean T1 or peak-location for either NAWM or GM. There was weak evidence for a decline in patient NAWM peak-height and also evidence for a decline in control GM peak-height. Conclusion There are significant and persistent abnormalities of NAWM and GM T1 in early relapsing-remitting MS. Further studies should address whether such T1 measures have a role in prognosis or therapeutic monitoring. Multiple Sclerosis 2007; 13:169–177. http://msj.sagepub.com

[1]  I. Allen,et al.  A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis , 1979, Journal of the Neurological Sciences.

[2]  G. Barker,et al.  Nuclear magnetic resonance relaxation in multiple sclerosis. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[3]  A J Thompson,et al.  Gray and white matter volume changes in early RRMS , 2005, Neurology.

[4]  A J Thompson,et al.  Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis , 2003, Multiple sclerosis.

[5]  F Barkhof,et al.  Neuronal damage in T1‐hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy , 1999, Annals of neurology.

[6]  R H Edwards,et al.  Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the "invisible" lesion load. , 1994, Magnetic resonance imaging.

[7]  J. Ashburner,et al.  Multimodal Image Coregistration and Partitioning—A Unified Framework , 1997, NeuroImage.

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

[9]  S. Hickman,et al.  Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis , 2001, Journal of the Neurological Sciences.

[10]  G. Barker,et al.  Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis , 1999, Neurology.

[11]  D. N. Landon,et al.  The characterization of experimental gliosis by quantitative nuclear magnetic resonance imaging. , 1988, Brain : a journal of neurology.

[12]  P A Rinck,et al.  Nuclear relaxation of human brain gray and white matter: Analysis of field dependence and implications for MRI , 1990, Magnetic resonance in medicine.

[13]  P. Matthews,et al.  White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis , 2002, Journal of Neurology.

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

[15]  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.

[16]  H. Goldstein.  Multilevel Statistical Models , 2006 .

[17]  Paul S. Morgan,et al.  White matter T1 relaxation time histograms and cerebral atrophy in multiple sclerosis , 2002, Journal of the Neurological Sciences.

[18]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[19]  G. Johnson,et al.  Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose intravenous methylprednisolone. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[20]  David H. Miller,et al.  The relationship between lesion and normal appearing brain tissue abnormalities in early relapsing remitting multiple sclerosis , 2002, Journal of Neurology.

[21]  A. Thompson,et al.  Metabolite changes in early relapsing–remitting multiple sclerosis , 2006, Journal of Neurology.

[22]  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.

[23]  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.

[24]  V. Haughton,et al.  Quantitative MR in the diagnosis of multiple sclerosis , 1992, Magnetic resonance in medicine.

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

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

[27]  P Kapeller,et al.  Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis. , 2002, Brain : a journal of neurology.

[28]  Nikos Evangelou,et al.  Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis , 2000, Annals of neurology.

[29]  M Filippi,et al.  A Magnetization Transfer Imaging Study of Normal-Appearing White Matter in Multiple Sclerosis , 1995, Neurology.

[30]  P M Matthews,et al.  Imaging axonal damage of normal-appearing white matter in multiple sclerosis. , 1998, Brain : a journal of neurology.

[31]  David H. Miller,et al.  A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. , 2002, The New England journal of medicine.

[32]  W. Mcdonald,et al.  The longstanding MS lesion. A quantitative MRI and electron microscopic study. , 1991, Brain : a journal of neurology.

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

[34]  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 .

[35]  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.

[36]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

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

[38]  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.

[39]  L. Kappos,et al.  Clinical–MRI correlations in a European trial of interferon beta-1b in secondary progressive MS , 2001, Neurology.

[40]  A J Thompson,et al.  Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination. , 1999, Neurology.

[41]  G Johnson,et al.  Precise relaxation time measurements of normal‐appearing white matter in inflammatory central nervous system disease , 1989, Magnetic resonance in medicine.

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

[43]  Y Van Haverbeke,et al.  The uncommon longitudinal relaxation dispersion of human brain white matter , 1989, Magnetic resonance in medicine.

[44]  G. Barker,et al.  Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations , 2000, Journal of neurology, neurosurgery, and psychiatry.