Functional MRI

  • M. Filippi
  • M. A. Rocca
Part of the Topics in Neuroscience book series (TOPNEURO)


Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by a proteiform pattern of clinical manifestations and a highly variable evolution. During the past decade, significant efforts have been devoted to improving our understanding of the pathophysiology of MS, with the ultimate goal of identifying and monitoring treatment strategies that have the potential to modify the evolution of the disease positively.


Multiple Sclerosis Multiple Sclerosis Patient Optic Neuritis Supplementary Motor Area Functional Magnetic Resonance Imaging 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Arnold DL, Matthews PM, Francis G, Antel J (1990) Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med 14: 154–159PubMedCrossRefGoogle Scholar
  2. 2.
    De Stefano N, Narayanan S, Francis GS et al (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58: 65–70PubMedCrossRefGoogle Scholar
  3. 3.
    Filippi M, Bozzali M, Gambini A et al (2002) Whole brain N-acetylaspartate concentrations are reduced in patients presenting with clinically isolated syndromes suggestive of MS. J Neurol 249(Suppl 1 ): I /209Google Scholar
  4. 4.
    Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120: 393–399PubMedCrossRefGoogle Scholar
  5. 5.
    Trapp BD, Ransohoff R, Rudick R (1999) Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 12: 295–302PubMedCrossRefGoogle Scholar
  6. 6.
    Kidd D, Barkhof F, McConnel R et al (1999) Cortical lesions in multiple sclerosis. Brain 122: 17–26PubMedCrossRefGoogle Scholar
  7. 7.
    Brownell B, Hughes JT (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25: 315–320PubMedCrossRefGoogle Scholar
  8. 8.
    Peterson JW, Bo L, Mork S et al (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50: 389–400PubMedCrossRefGoogle Scholar
  9. 9.
    Ge Y, Grossman RI, Udupa JK et al (2002) Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis. J Comput Assist Tomogr 26: 62–68PubMedCrossRefGoogle Scholar
  10. 10.
    Cercignani M, Bozzali M, Iannucci G et al (2001) Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 70: 311–317PubMedCrossRefGoogle Scholar
  11. 11.
    Bozzali M, Cercignani M, Sormani MP et al (2002) Quantification of brain gray matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR Am J Neuroradiol 23: 985–988PubMedGoogle Scholar
  12. 12.
    Sarchielli P, Presciutti O, Tarducci R et al (2002) Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis. J Neurol 249: 902–910PubMedCrossRefGoogle Scholar
  13. 13.
    Lassmann H, Brück W, Lucchinetti C, Rodriguez M (1997) Remyelination in multiple sclerosis. Mult Scler 3: 133–136PubMedCrossRefGoogle Scholar
  14. 14.
    Waxman SG, Ritchie JM (1993) Molecular dissection of the myelinated axon. Ann Neurol 33: 121–136PubMedCrossRefGoogle Scholar
  15. 15.
    De Stefano N, Narayanan S, Matthews PM et al (1999) In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis. Brain 122: 1933–1939PubMedCrossRefGoogle Scholar
  16. 16.
    Waxman SG (2001) Acquired channelopathies in nerve injury and MS. Neurology 56: 1621–1627PubMedGoogle Scholar
  17. 17.
    Ogawa S, Menon RS, Tank DW et al (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64: 803–812PubMedCrossRefGoogle Scholar
  18. 18.
    Ogawa S, Menon RS, Kim SG, Ugurbil K (1998) On the characteristics of functional magnetic resonance imaging of the brain. Annu Rev Biophys Biomol Struct 27: 447–474PubMedCrossRefGoogle Scholar
  19. 19.
    Filippi M, Rocca MA (2002) Functional magnetic resonance imaging. In: Filippi M, Comi G (eds) Primary progressive multiple sclerosis. Springer, Milan, pp 111–124CrossRefGoogle Scholar
  20. 20.
    Vanzetta I, Grinvald A (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286: 1555–1558PubMedCrossRefGoogle Scholar
  21. 21.
    Bandettini PA, Jesmanowicz A, Wong EC, Hyde JS (1993) Processing strategies for time-course data sets in functional MRI of the human brain. Magn Reson Med 30: 161–173PubMedCrossRefGoogle Scholar
  22. 22.
    Worsley KJ, Friston KJ (1995) Analysis of fMRI time-series revisited-again. Neuroimage 2: 173–181PubMedCrossRefGoogle Scholar
  23. 23.
    Filippi M, Paty DW, Kappos L et al (1995) Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a follow-up study. Neurology 45: 255–260PubMedGoogle Scholar
  24. 24.
    Lycklama à Nijeholt GJ, van Walderveen MA, Castelijns JA et al (1998) Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain 121: 687–697CrossRefGoogle Scholar
  25. 25.
    Kappos L, Moeri D, Radue EW et al (1999) Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group. Lancet 353: 964–969PubMedCrossRefGoogle Scholar
  26. 26.
    De Stefano N, Matthews PM, Fu L et al (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121: 1469–1477PubMedCrossRefGoogle Scholar
  27. 27.
    Filippi M (2001) Linking structural, metabolic and functional changes in multiple sclerosis. Eur J Neurol 8: 291–297PubMedCrossRefGoogle Scholar
  28. 28.
    Mainero C, De Stefano N, Iannucci G et al (2001) Correlates of MS disability assessed in vivo using aggregates of MR quantities. Neurology 56: 1331–1334PubMedGoogle Scholar
  29. 29.
    Clanet M, Berry I, Boulanouar K (1997) Functional imaging in multiple sclerosis. Int MS J 4: 26–32Google Scholar
  30. 30.
    Lee M, Reddy H, Johansen-Berg H et al (2000) The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neurol 47: 606–613PubMedCrossRefGoogle Scholar
  31. 31.
    Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343: 938–952PubMedCrossRefGoogle Scholar
  32. 32.
    Iannucci G, Tortorella C, Rovaris M et al (2000) Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. AJNR Am J Neuroradiol 21: 1034–1038PubMedGoogle Scholar
  33. 33.
    Brex PA, Jenkins R, Fox NC et al (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54: 1689–1691PubMedGoogle Scholar
  34. 34.
    Filippi M, Inglese M, Rovaris M et al (2000) Magnetization transfer imaging to monitor the evolution of MS: a 1-year follow-up study. Neurology 55: 940–946PubMedGoogle Scholar
  35. 35.
    Rudick RA, Fisher E, Lee JC et al (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multi Scler Collaborative Research Group. Neurology 53: 1698–1704PubMedGoogle Scholar
  36. 36.
    Chard DT, Griffin CM, Parker GJ et al (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125: 327–337PubMedCrossRefGoogle Scholar
  37. 37.
    Kapeller P, McLean MA, Griffin CM et al (2001) Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol 248: 131–138PubMedCrossRefGoogle Scholar
  38. 38.
    Werring DJ, Bullmore ET, Toosy AT et al (2000) Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study. J Neurol Neurosurg Psychiatry 68: 441–449PubMedCrossRefGoogle Scholar
  39. 39.
    Filippi M, Rocca MA, Falini A et al (2002) A functional MRI study of patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. J Neurol 249 (Suppl 1 ): I /20Google Scholar
  40. 40.
    Pantano P, Iannetti GD, Caramia F et al (2002) Cortical motor reorganization after a single clinical attack of multiple sclerosis. Brain 125: 1607–1615PubMedCrossRefGoogle Scholar
  41. 41.
    Mesulam MM (1998) From sensation to cognition. Brain 121: 1013–1052PubMedCrossRefGoogle Scholar
  42. 42.
    McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 50: 121–127PubMedCrossRefGoogle Scholar
  43. 43.
    Reddy H, Narayanan S, Matthews PM et al (2000) Relating axonal injury to functional recovery in MS. Neurology 54: 236–239PubMedGoogle Scholar
  44. 44.
    Filippi M, Iannucci G, Tortorella C et al (1999) Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI. Neurology 52: 588–594PubMedGoogle Scholar
  45. 45.
    Rocca MA, Falini A, Colombo B et al (2002) Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol 51: 330–339PubMedCrossRefGoogle Scholar
  46. 46.
    Filippi M, Rocca MA, Colombo B et al (2002) Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage 15: 559–567PubMedCrossRefGoogle Scholar
  47. 47.
    Rombouts SA, Lazeron RH, Scheltens P et al (1998) Visual activation patterns in patients with optic neuritis: an fMRI pilot study. Neurology 50: 1896–1899PubMedGoogle Scholar
  48. 48.
    Langkilde AR, Frederiksen JL, Rostrup E, Larsson HB (2002) Functional MRI of the visual cortex and visual testing in patients with previous optic neuritis. Eur J Neurol 9: 277–286PubMedCrossRefGoogle Scholar
  49. 49.
    Reddy H, Narayanan S, Arnoutelis R et al (2000) Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain 123: 2314–2320PubMedCrossRefGoogle Scholar
  50. 50.
    Filippi M, Rocca MA, Minicucci L et al (1999) Magnetization transfer imaging of patients with definite MS and negative conventional MRI. Neurology 52: 845–848PubMedGoogle Scholar
  51. 51.
    Filippi M, Rocca MA, Pagani E et al (2002) Functional cortical changes in patients with MS and non-specific findings on conventional MRI scans of the brain. Neuroimage.Google Scholar
  52. 52.
    Liepert J, Dettmers C, Terborg C, Weiller C (2001) Inhibition of ipsilateral motor cortex during phasic generation of low force. Clin Neurophysiol 112: 114–121PubMedCrossRefGoogle Scholar
  53. 53.
    Lowe MJ, Phillips MD, Lurito JT et al (2002) Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity initial results. Radiology 224: 184–192PubMedCrossRefGoogle Scholar
  54. 54.
    Reddy H, Narayanan S, Mitsumori T et al (2002) Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. Brain.Google Scholar
  55. 55.
    Staffen W, Mair A, Zauner H et al (2002) Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task. Brain 125: 1275–1282PubMedCrossRefGoogle Scholar
  56. 59.
    Thompson AJ, Montalban X, Barkhof F et al (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47: 831–835PubMedCrossRefGoogle Scholar
  57. 57.
    Thompson AJ, Kermode AG, Wicks D et al (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29: 53–62PubMedCrossRefGoogle Scholar
  58. 58.
    Kidd D, Thorpe JW, Kendall BE et al (1996) MRI dynamics of brain and spinal cord in progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 60: 15–19PubMedCrossRefGoogle Scholar
  59. 59.
    Stevenson VL, Miller DH, Rovaris M et al (1999) Primary and transitional progressive MS: a clinical and MRI cross-sectional study. Neurology 52: 839–845PubMedGoogle Scholar
  60. 60.
    Stevenson VL, Miller DH, Leary SM et al (2000) One year follow up study of primary and transitional progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 68: 713–718PubMedCrossRefGoogle Scholar
  61. 61.
    Leary SM, Davie CA, Parker GJ et al (1999) 1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis. J Neurol 246: 1023–1026Google Scholar
  62. 62.
    Leary SM, Silver NC, Stevenson VL et al (1999) Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis. Mult Scler 5: 313–316PubMedGoogle Scholar
  63. 63.
    Rovaris M, Bozzali M, Santuccio G et al (2001) In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 124: 2540–2549PubMedCrossRefGoogle Scholar
  64. 64.
    Rocca MA, Matthews PM, Caputo D et al (2002) Evidence for widespread movement-associated functional MRI changes in patients with PPMS. Neurology 58: 866–872PubMedGoogle Scholar
  65. 65.
    Filippi M, Rocca MA, Falini A et al (2002) Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 15: 537–546PubMedCrossRefGoogle Scholar
  66. 66.
    Rao SM, Binder JR, Bandettini PA et al (1993) Functional magnetic resonance imaging of complex human movements. Neurology 43: 2311–2318PubMedGoogle Scholar
  67. 67.
    Paus T, Petrides M, Evans AC, Meyer E (1993) Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. J Neurophysiol 70: 453–469PubMedGoogle Scholar
  68. 68.
    Jenkins IH, Brooks DJ, Nixon PD et al (1994) Motor sequence learning: a study with positron emission tomography. J Neurosci 14: 3775–3790PubMedGoogle Scholar
  69. 69.
    de Gelder B (2000) Neuroscience. More to seeing than meets the eye. Science 289: 1148–1149PubMedCrossRefGoogle Scholar
  70. 70.
    van Waesberghe JH, Kamphorst W, De Groot CJ et al (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46: 747–754PubMedCrossRefGoogle Scholar
  71. 71.
    Pierpaoli C, Jezzard P, Basser PJ et al (1996) Diffusion tensor MR imaging of the human brain. Radiology 201: 637–648PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 2003

Authors and Affiliations

  • M. Filippi
  • M. A. Rocca

There are no affiliations available

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