MRI techniques to monitor MS evolution: The present and the future

Abstract—Conventional MRI (cMRI) is limited in its ability to provide specific information about pathology in MS. Measures commonly derived from cMRI include T2 lesions, T1-enhanced lesions, atrophy, and possibly T1-hypointense lesions, which have been extensively investigated in many clinical trials. Better MRI measures are needed to advance our understanding of MS and design ideal clinical trials. This article reviews the strengths and weaknesses of the major MRI-based methods used to monitor MS evolution and submits that 1) metrics derived from magnetization transfer MRI, diffusion-weighted MRI, and proton MRS should be implemented to achieve reliable specific in vivo quantification of MS pathology; 2) targeted multiparametric MRI protocols rather than generic application of cMRI should be used in all possible clinical circumstances and trials; and 3) reproducible quantitative MR measures should ideally be used for the assessment of patients but are essential for clinical trials.

[1]  R. Rudick,et al.  Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS , 1999, Neurology.

[2]  M. Rovaris,et al.  Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy , 2001, Journal of neurology, neurosurgery, and psychiatry.

[3]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[4]  M Rovaris,et al.  Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis , 1998, Neurology.

[5]  M Filippi,et al.  Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI , 1999, Neurology.

[6]  M Rovaris,et al.  Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[7]  G. Comi,et al.  Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium , 1998, Neurology.

[8]  L. Wilkins,et al.  Fear recognition deficits after focal brain damage , 2000, Neurology.

[9]  R I Grossman,et al.  Total brain N-acetylaspartate , 2000, Neurology.

[10]  B K Rutt,et al.  Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS , 2000, Journal of magnetic resonance imaging : JMRI.

[11]  P M Matthews,et al.  Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. , 1996, Brain : a journal of neurology.

[12]  P M Matthews,et al.  Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. , 2001, Archives of neurology.

[13]  Hans Lassmann,et al.  Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology , 1997, Annals of neurology.

[14]  Jullie W Pan,et al.  Evaluation of multiple sclerosis by 1H spectroscopic imaging at 4.1 T , 1996, Magnetic resonance in medicine.

[15]  P M Matthews,et al.  The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis , 2000, Annals of neurology.

[16]  M S Buchsbaum,et al.  Whole-brain diffusion MR histograms differ between MS subtypes , 2000, Neurology.

[17]  G. Barker,et al.  Correlation of magnetization transfer ration with clinical disability in multiple sclerosis , 1994, Annals of neurology.

[18]  F. Barkhof,et al.  Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis , 1998, Neurology.

[19]  M Filippi,et al.  Linking structural, metabolic and functional changes in multiple sclerosis , 2001, European journal of neurology.

[20]  M. Rovaris,et al.  Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[21]  G. Comi,et al.  Magnetization-transfer histogram analysis of the cervical cord in patients with multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[22]  Ludwig Kappos,et al.  Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis , 1999, The Lancet.

[23]  M Filippi,et al.  Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[24]  P M Matthews,et al.  Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. , 1998, Brain : a journal of neurology.

[25]  J. Taubenberger,et al.  Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis , 1993, Annals of neurology.

[26]  G. Comi,et al.  Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI , 2000, Neurology.

[27]  C Delalande,et al.  Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis. , 1999, AJNR. American journal of neuroradiology.

[28]  S. Rose,et al.  Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[29]  T. Iwasawa,et al.  Diffusion‐weighted imaging of the human optic nerve: A New approach to evaluate optic neuritis in multiple sclerosis , 1997, Magnetic resonance in medicine.

[30]  J K Udupa,et al.  Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis. , 2001, AJNR. American journal of neuroradiology.

[31]  G J Barker,et al.  Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. , 1994, Brain : a journal of neurology.

[32]  M Cercignani,et al.  Diffusion tensor magnetic resonance imaging in multiple sclerosis , 2001, Neurology.

[33]  F. Barkhof,et al.  Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis. , 2001, Archives of neurology.

[34]  R I Grossman,et al.  Dyke Award paper. MR of wallerian degeneration in the feline visual system: characterization by magnetization transfer rate with histopathologic correlation. , 1994, AJNR. American journal of neuroradiology.

[35]  M Rovaris,et al.  Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications. , 2001, Brain : a journal of neurology.

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

[37]  B Quesson,et al.  In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance , 1999, Magnetic resonance in medicine.

[38]  B. I. Hendriks-Stegeman,et al.  A Novel Nonsense Mutation of the KAL Gene in Two Brothers withKallmann Syndrome , 2000, Hormone Research in Paediatrics.

[39]  F. Barkhof,et al.  Axonal loss in multiple sclerosis lesions: Magnetic resonance imaging insights into substrates of disability , 1999, Annals of neurology.

[40]  F. Barkhof,et al.  Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis , 1996, Neurology.

[41]  C. Lucchinetti,et al.  A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions , 2001, Annals of neurology.

[42]  M Cercignani,et al.  Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers. , 2000, AJNR. American journal of neuroradiology.

[43]  C Caltagirone,et al.  Demyelinating plaques in relapsing-remitting and secondary-progressive multiple sclerosis: assessment with diffusion MR imaging. , 2000, AJNR. American journal of neuroradiology.

[44]  G. Scotti,et al.  Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI , 2001, Neurology.

[45]  R E Lenkinski,et al.  MR proton spectroscopy in multiple sclerosis. , 1992, AJNR. American journal of neuroradiology.

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

[47]  G. Comi,et al.  Magnetization transfer imaging to monitor the evolution of MS , 2000, Neurology.

[48]  F. Barkhof,et al.  Cortical lesions in multiple sclerosis. , 1999, Brain : a journal of neurology.

[49]  Kenneth J. Smith,et al.  Multiple sclerosis: more than inflammation and demyelination , 2001, Trends in Neurosciences.

[50]  David H. Miller,et al.  Diffusion imaging of the spinal cord in vivo: Estimation of the principal diffusivities and application to multiple sclerosis , 2000, Magnetic resonance in medicine.

[51]  C. Mainero,et al.  Correlates of MS disability assessed in vivo using aggregates of MR quantities , 2001, Neurology.

[52]  F. Barkhof,et al.  Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. , 1998, AJNR. American journal of neuroradiology.

[53]  H. Hanyu,et al.  Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease , 1998, Journal of the Neurological Sciences.

[54]  G. Fein,et al.  Biochemical alterations in multiple sclerosis lesions and normal‐appearing white matter detected by in vivo 31P and 1H spectroscopic imaging , 1994, Annals of neurology.

[55]  M Filippi,et al.  A magnetization transfer histogram study of normal-appearing brain tissue in MS , 2000, Neurology.

[56]  M W Weiner,et al.  A serial study of new MS lesions and the white matter from which they arise , 1998, Neurology.

[57]  P M Matthews,et al.  Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. , 2000, Brain : a journal of neurology.

[58]  J. Caillé,et al.  Early structural changes in acute MS lesions assessed by serial magnetization transfer studies , 1998, Neurology.

[59]  J. Coyle,et al.  Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies , 1991, Neuroscience.

[60]  R E Lenkinski,et al.  Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation. , 1996, Journal of computer assisted tomography.

[61]  M. Horsfield,et al.  A conventional and magnetization transfer MRI study of the cervical cord in patients with MS , 2000, Neurology.

[62]  J K Udupa,et al.  Correlation of volumetric magnetization transfer imaging with clinical data in MS , 1998, Neurology.

[63]  Massimo Filippi,et al.  Multiple sclerosis: a white matter disease with associated gray matter damage , 2001, Journal of the Neurological Sciences.

[64]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[65]  P. Tofts.  Modeling tracer kinetics in dynamic Gd‐DTPA MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[66]  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.

[67]  A. Thompson,et al.  Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. , 1996, Brain : a journal of neurology.

[68]  A Benazzouz,et al.  Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization transfer. , 1995, AJNR. American journal of neuroradiology.

[69]  M Rovaris,et al.  Whole brain volume changes in patients with progressive MS treated with cladribine , 2000, Neurology.

[70]  J A Frank,et al.  Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis , 1998, Annals of neurology.

[71]  M Filippi,et al.  Correlations between clinical and MRI involvement in multiple sclerosis: assessment using T1, T2 and MT histograms , 1999, Journal of the Neurological Sciences.

[72]  P. Matthews,et al.  Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis , 1994, Annals of neurology.

[73]  J. Wolinsky,et al.  Linomide in relapsing and secondary progressive MS , 2000, Neurology.

[74]  P. Thompson,et al.  Exacerbation of postural tremor with emergence of parkinsonism after treatment with neuroleptic drugs. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[75]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[76]  R I Grossman,et al.  Quantitative volumetric magnetization transfer analysis in multiple sclerosis: Estimation of macroscopic and microscopic disease burden , 1996, Magnetic resonance in medicine.

[77]  P. Matthews,et al.  Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. , 2000, Brain : a journal of neurology.

[78]  S. Reingold,et al.  Placebo‐controlled clinical trials in multiple sclerosis: Ethical considerations , 2001, Annals of neurology.

[79]  M Filippi,et al.  Characteristics of chronic MS lesions in the cerebrum, brainstem, spinal cord, and optic nerve on T1‐‐‐weighted MRI , 1998, Neurology.

[80]  G. Comi,et al.  Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis. , 2001, AJNR. American journal of neuroradiology.

[81]  A J Thompson,et al.  Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. , 1996, Brain : a journal of neurology.

[82]  P. C. de Freitas Mathias,et al.  Insulin Secretion and Acetylcholinesterase Activity in Monosodium L-Glutamate-Induced Obese Mice , 2001, Hormone Research in Paediatrics.

[83]  M. Filippi,et al.  Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement , 1998, Journal of the Neurological Sciences.

[84]  J H Simon,et al.  A longitudinal study of T1 hypointense lesions in relapsing MS , 2000, Neurology.