, Volume 2, Issue 2, pp 277–303 | Cite as

Imaging of multiple sclerosis: Role in neurotherapeutics

  • Rohit Bakshi
  • Alireza Minagar
  • Zeenat Jaisani
  • Jerry S. Wolinsky


Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Key Words

Multiple sclerosis magnetic resonance imaging brain atrophy diffusion imaging magnetization transfer spectroscopy functional imaging 


  1. 1.
    McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis.Ann Neurol 121–127, 2001.Google Scholar
  2. 2.
    Miller DH, Filippi M, Fazekas F, Federiksen JL, Matthews PM, Montalban X, et al. Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis.Ann Neurol 56: 273–278, 2004.PubMedGoogle Scholar
  3. 3.
    Barkhof F, Rocca M, Francis G, Van Waesberghe JH, Uitdehaag BM, Hommes OR, et al. Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon β1a.Ann Neurol 53: 718–724, 2003.PubMedGoogle Scholar
  4. 4.
    Zivadinov R, Bakshi R. Role of MRI in multiple sclerosis I: inflammation and lesions.Front Biosci 9: 665–683, 2004.PubMedGoogle Scholar
  5. 5.
    Lai M, Hodgson T, Gawne-Cain M, Webb S, MacManus D, McDonald WI, et al. A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis.J Neurol Neurosurg Psychiatry 60: 339–341, 1996.PubMedGoogle Scholar
  6. 6.
    Bakshi R, Hutton GJ, Miller JR, Radue EW. The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis.Neurology 63(Suppl 5): S3-S11, 2004.PubMedGoogle Scholar
  7. 7.
    Bagnato F, Jeffries N, Richert ND, Stone RD, Ohayon JM, McFarland HF, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years.Brain 126: 1782–1789, 2003.PubMedGoogle Scholar
  8. 8.
    Filippi M, Rovaris M, Rocca MA, Sormani MP, Wolinsky JS, Comi G. Glatiramer acetate reduces the proportion of new MS lesions evolving into “black holes.”Neurology 57: 731–733, 2001.PubMedGoogle Scholar
  9. 9.
    Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, et al. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance.Arch Neurol 60: 1073–1081, 2003.PubMedGoogle Scholar
  10. 10.
    Masdeu JC, Quinto C, Olivera C, Tenner M, Leslie D, Visintainer P. Open-ring imaging sign: highly specific for atypical brain demyelination.Neurology 54: 1427–1433, 2000.PubMedGoogle Scholar
  11. 11.
    Wolinsky JS, Narayana PA, Noseworthy JH, Lublin FD, Whitaker JN, Linde A, et al. Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators.Neurology 54: 1734–1741, 2000.PubMedGoogle Scholar
  12. 12.
    Filippi M, Wolinsky JS, Sormani MP, Comi G, European Canadian Glatiramer Acetate Study Group. Enhancement frequency decreases with increasing age in relapsing-remitting multiple sclerosis.Neurology 56: 422–423, 2001PubMedGoogle Scholar
  13. 13.
    Richert ND, Ostuni JL, Bash CN, Leist TP, McFarland HF, Frank JA. Interferon β-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis.Mult Scler 7: 49–58, 2001.PubMedGoogle Scholar
  14. 14.
    Laule C, Vavasour IM, Whittall KP, Oger J, Paty DW, Li DK, et al. Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis.J Neurol 250: 924–931, 2003.PubMedGoogle Scholar
  15. 15.
    Narayana PA, Doyle TJ, Lai D, Wolinsky JS. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis.Ann Neurol 43: 56–71, 1998.PubMedGoogle Scholar
  16. 16.
    Tartaglia MC, Narayanan S, De Stefano N, Amaoutelis R, Antel SB, Francis SJ, et al. Choline is increased in pre-lesional normal appearing white matter in multiple sclerosis.J Neurol 249: 1382–1390, 2002.PubMedGoogle Scholar
  17. 17.
    Wolinsky JS, Narayana PA. Magnetic resonance spectroscopy in multiple sclerosis: window into the diseased brain.Curr Opin Neurol 15: 247–251, 2002.PubMedGoogle Scholar
  18. 18.
    Helms G, Stawiarz L, Kivisakk P, Link H. Regression analysis of metabolite concentrations estimated from localized proton MR spectra of active and chronic multiple sclerosis lesions.Magn Reson Med 43: 102–110, 2000.PubMedGoogle Scholar
  19. 19.
    van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijn JA, Ravid R, et al. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability.Ann Neurol 46: 747–754, 1999.PubMedGoogle Scholar
  20. 20.
    Castriota-Scanderbeg A, Fasano F, Hagberg G, Nocentini U, Filippi M, Caltagirone C. Coefficient D(av) is more sensitive than fractional anisotropy in monitoring progression of irreversible tissue damage in focal nonactive multiple sclerosis lesions.AJNR Am J Neuroradiol 24: 663–670, 2003.PubMedGoogle Scholar
  21. 21.
    Henry RG, Oh J, Nelson SJ, Pelletier D. Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.J Magn Reson Imaging 18: 420–426, 2003.PubMedGoogle Scholar
  22. 22.
    Sharma R, Narayana PA, Wolinsky JS. Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging.Mult Scler 7: 221–226, 2001.PubMedGoogle Scholar
  23. 23.
    Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ. Intracortical multiple sclerosis lesions are not associated with increased lym-phocyte infiltration.Mult Scler 9: 323–331, 2003.PubMedGoogle Scholar
  24. 24.
    Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination.Ann Neurol 47: 707–717, 2000.PubMedGoogle Scholar
  25. 25.
    Stewart WA, Hall LD, Berry K, Paty DW. Correlation between NMR scan and brain slice data in multiple sclerosis.Lancet 2: 412, 1984.PubMedGoogle Scholar
  26. 26.
    Moore GR, Leung E, MacKay AL, Vavasour IM, Whittall KP, Cover KS, et al. A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain.Neurology 55: 1506–1510, 2000.PubMedGoogle Scholar
  27. 27.
    Bo L, Geurts JJ, Ravid R, Barkhof F. Magnetic resonance imaging as a tool to examine the neuropathology of multiple sclerosis.Neuropathol Appl Neurobiol 30: 106–117, 2004.PubMedGoogle Scholar
  28. 28.
    Schmierer K, Scaravilli F, Barker GJ, Gordon R, MacManus DG, Miller DH. Stereotactic co-registration of magnetic resonance imaging and histopathology in post-mortem multiple sclerosis brain.Neuropathol Appl Neurobiol 29: 596–601, 2003.PubMedGoogle Scholar
  29. 29.
    Newcombe J, Hawkins CP, Henderson CL, Patel HA, Woodroofe MN, Hayes GM, et al. Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue.Brain 114: 1013–1023, 1991.PubMedGoogle Scholar
  30. 30.
    Bakshi R, Benedict RHB, Beimel RA, Jacobs L. Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative MRI and relationship to clinical findings.J Neuroimaging 11: 129–136, 2001.PubMedGoogle Scholar
  31. 31.
    Rovaris M, Comi G, Ladkani D, Wolinsky JS, Filippi M. Short-term correlations between clinical and MR imaging findings in relapsing-remitting multiple sclerosis.AJNR Am J Neuroradiol 24: 75–81, 2003.PubMedGoogle Scholar
  32. 32.
    Barkhof F. MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS).Mult Scler 5: 283–286, 1999.PubMedGoogle Scholar
  33. 33.
    Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.Lancet 357: 1576–1582, 2001.PubMedGoogle Scholar
  34. 34.
    Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.N Engl J Med 346: 158–164, 2002.PubMedGoogle Scholar
  35. 35.
    Filippi M, Horsfield MA, Morrissey SP, MacManus DG, Rudge P, McDonald WI, et al. Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis.Neurology 44: 635–641, 1994.PubMedGoogle Scholar
  36. 36.
    O’Riordan JI, Thompson AJ, Kingsley DP, MacManus DG, Kendall BE, Rudge P, et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.Brain 121: 495–503, 1998.PubMedGoogle Scholar
  37. 37.
    Fazekas F, Barkhof F, Filippi M, Grossman RI, Li DK, McDonald WI, et al. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis.Neurology 53: 448–456, 1999.PubMedGoogle Scholar
  38. 38.
    Brex PA, Miszkiel KA, O’Riordan JI, Plant GT, Moseley IF, Thompson AJ, et al. Assessing the risk of early multiple sclerosis in patients with clinically isolated syndromes: the role of a follow up MRI.J Neurol Neurosurg Psychiatry 70: 390–393, 2001.PubMedGoogle Scholar
  39. 39.
    Dalton CM, Brex PA, Miszkiel KA, Fernando K, MacManus DG, Plant GT, et al. New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes.Ann Neurol 53: 673–676, 2003.PubMedGoogle Scholar
  40. 40.
    Jacobs LD, Beck RW, Simon JH, Kinkel RP, Browscheidle CM, Murray TJ, et al. Intramuscular interferon β-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.N Engl J Med 343: 898–904, 2000.PubMedGoogle Scholar
  41. 41.
    CHAMPS Study Group. Baseline MRI characteristics of patients at high risk for multiple sclerosis: results from the CHAMPS trial. Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study.Mult Scler 8: 330–338, 2002Google Scholar
  42. 42.
    Kappos L, Patzold U, Dommasch D, Poser S, Haas J, Krauseneck P, et al. Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis-results of the German multicenter study.Ann Neurol 23: 56–63, 1988.PubMedGoogle Scholar
  43. 43.
    Kappos L, Stadt D, Ratzka M, Keil W, Schneiderbanger-Grygier S, Heitzer T, et al. Magnetic resonance imaging in the evaluation of treatment in multiple sclerosis.Neuroradiology 30: 299–302, 1988.PubMedGoogle Scholar
  44. 44.
    The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial.Ann Neurol 27: 591–605, 1990.Google Scholar
  45. 45.
    Zhao GJ, Li DK, Wolinsky JS, Koopmans RA, Mietlowski W, Redekop WK, et al. Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis. The MS Study Group.J Neuroimaging 7: 1–7, 1997.PubMedGoogle Scholar
  46. 46.
    Paty DW, Li DK. Interferon β-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/ MRI Study Group and the IFNB Multiple Sclerosis Study Group.Neurology 43: 662–667, 1993.PubMedGoogle Scholar
  47. 47.
    Filippi M, Horsfield MA, Ader HJ, Barkhof F, Bruzzi P, Evans A, et al. Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis.Ann Neurol 43: 499–506, 1998.PubMedGoogle Scholar
  48. 48.
    Li DK, Paty DW. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-β1a in relapsing-remitting multiple sclerosis.Ann Neurol 46: 197–206, 1999.PubMedGoogle Scholar
  49. 49.
    Li DK, Zhao GJ, Paty DW; University of British Columbia MS/ MRI Analysis Research Group. Randomized controlled trial of interferon-β-1a in secondary progressive MS: MRI results.Neurology 56: 1505–1513, 2001.PubMedGoogle Scholar
  50. 50.
    Miller DH, Molyneux PD, Barker GJ, MacManus DG, Moseley IF, Wagner K. Effect of interferon-β1b on magnetic resonance imaging outcomes in secondary progressive multiple sclerosis: results of a European multicenter, randomized, double-blind, placebo-controlled trial. European Study Group on Interferon-β1b in secondary progressive multiple sclerosis.Ann Neurol 46: 850–859, 1999.PubMedGoogle Scholar
  51. 51.
    Comi G, Filippi M, Wolinsky JS. European/Canadian multi-center, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging— measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group.Ann Neurol 49: 290–297, 2001.PubMedGoogle Scholar
  52. 52.
    Molyneux PD, Miller DH, Filippi M, Yousry T, Kappos L, Gasperini C, et al. The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement.J Neurol 247: 34–40, 2000.PubMedGoogle Scholar
  53. 53.
    Silver NC, Good CD, Barker GJ, MacManus DG, Thompson AJ, Moseley IF, et al. Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging.Brain 120: 1149–1161, 1997.PubMedGoogle Scholar
  54. 54.
    Wolansky LJ, Bardini JA, Cook SD, Zimmer AE, Sheffet A, Lee HJ. Triple-dose versus single-dose gadoteridol in multiple sclerosis patients.J Neuroimaging 4: 141–145, 1994.PubMedGoogle Scholar
  55. 55.
    Nesbit GM, Forbes GS, Scheithauer BW, Okazaki H, Rodriguez M. Multiple sclerosis: histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy.Radiology 180: 467–474, 1991.PubMedGoogle Scholar
  56. 56.
    Katz D, Taubenberger JK, Cannella B, McFarlin DE, Raine CS, McFarland HF. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis.Ann Neurol 34: 661–669, 1993.PubMedGoogle Scholar
  57. 57.
    Brack W, Bitsch A, Kolenda H, Brack Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology.Ann Neurol 42: 783–793, 1997.Google Scholar
  58. 58.
    Kupersmith MJ, Alban T, Zeiffer B, Lefton D. Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance.Brain 125: 812–822, 2002.PubMedGoogle Scholar
  59. 59.
    Youl BD, Turano G, Miller DH, Towell AD, MacManus DG, Moore SG, et al. The pathophysiology of acute optic neuritis. An association of gadolinium leakage with clinical and electrophysiological deficits.Brain 114: 2437–2450, 1991.PubMedGoogle Scholar
  60. 60.
    McFarland HF, Stone LA, Calabresi PA, Maloni H, Bash CN, Frank JA. MRI studies of multiple sclerosis: implications for the natural history of the disease and for monitoring effectiveness of experimental therapies.Mult Scler 2: 198–205, 1996.PubMedGoogle Scholar
  61. 61.
    Kappos L, Moeri D, Radue EW, Schoetzau A, Schweikert K, Barkhof F, 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. Gadolinium MRI Meta-analysis Group.Lancet 353: 964–969, 1999.PubMedGoogle Scholar
  62. 62.
    Ebers G, for the PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis.Lancet 352: 1498–1504, 1998.Google Scholar
  63. 63.
    Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis.N Engl J Med 348: 15–23, 2003.PubMedGoogle Scholar
  64. 64.
    Kappos L, for the European Study Group on interferon β-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis.Lancet 352: 1491–1497, 1998.Google Scholar
  65. 65.
    Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group.Neurology 54: 1145–1155, 2000.PubMedGoogle Scholar
  66. 66.
    Sormani MP, Molyneux PD, Gasperini C, Barkhof F, Yousry TA, Miller DH, et al. Statistical power of MRI monitored trials in multiple sclerosis: new data and comparison with previous results.J Neurol Neurosurg Psychiatry 66: 465–469, 1999.PubMedGoogle Scholar
  67. 67.
    Sormani MP, Miller DH, Comi G, Barkhof F, Rovaris M, Bruzzi P, et al. Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets.J Neurol Neurosurg Psychiatry 70: 494–499, 2001.PubMedGoogle Scholar
  68. 68.
    Sormani MP, Rovaris M, Bagnato F, Molyneux P, Bruzzi P, Pozzilli C, et al. Sample size estimations for MRI-monitored trials of MS comparing new vs standard treatments.Neurology 57: 1883–1885, 2001.PubMedGoogle Scholar
  69. 69.
    Filippi M, Rovaris M, Capra R, Gasperini C, Yousry TA, Sormani MP, et al. A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials.Brain 121: 2011–2020, 1998.PubMedGoogle Scholar
  70. 70.
    Rovaris M, Capra R, Martinelli V, Gasperini C, Prandini F, Pozzilli C, et al. Cumulative effect of a weekly low dose of interferon β 1a on standard and triple dose contrast-enhanced MRI from multiple sclerosis patients.J Neurol Sci 171: 130–134, 1999.PubMedGoogle Scholar
  71. 71.
    Rovaris M, Codella M, Moiola L, Ghezzi A, Zaffaroni M, Mancardi G, et al. Effect of glatiramer acetate on MS lesions enhancing at different gadolinium doses.Neurology 59: 1429–1432, 2002.PubMedGoogle Scholar
  72. 72.
    TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group.Neurology 53: 457–465, 1999.Google Scholar
  73. 73.
    Bielekova B, Goodwin B, Richert N, Cortese I, Kondo T, Afshar G, et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.Nat Med 6: 1167–1175, 2000.PubMedGoogle Scholar
  74. 74.
    Barkhof F, McGowan JC, van Waesberghe JH, Grossman RI. Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic resonance images: their contribution in understanding multiple sclerosis evolution.J Neurol Neurosurg Psychiatry 64(Suppl 1): S77-S79, 1998.PubMedGoogle Scholar
  75. 75.
    Rovaris M, Comi G, Rocca MA, Cercignani M, Colombo B, Santuccio G, et al. Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis.AJNR Am J Neuroradiol 20: 813–820, 1999.PubMedGoogle Scholar
  76. 76.
    Ciccarelli O, Giugni E, Paolillo A, Mainero C, Gasperini C, Bastianello S, et al. Magnetic resonance outcome of new enhancing lesions in patients with relapsing-remitting multiple sclerosis.Eur J Neurol 6: 455–459, 1999.PubMedGoogle Scholar
  77. 77.
    Bitsch A, Kuhlmann T, Stadelmann C, Lassmann H, Lucchinetti C, Brueck W. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions.Ann Neurol 49: 793–796, 2001.PubMedGoogle Scholar
  78. 78.
    Leist TP, Gobbini MI, Frank JA, McFarland HF. Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis.Arch Neurol 58: 57–60, 2001.PubMedGoogle Scholar
  79. 79.
    van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, Valk J, et al. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis.Neurology 50: 1282–1288, 1998.PubMedGoogle Scholar
  80. 80.
    Meier DS, Weiner HL, Khoury SJ, Guttmann CR. Magnetic resonance imaging surrogates of multiple sclerosis pathology and their relationship to central nervous system atrophy.J Neuroimaging 14(Suppl 3): 46S-53S, 2004.PubMedGoogle Scholar
  81. 81.
    van Walderveen MA, Barkhof F, Pouwels PJ, van Schijndel RA, Polman CH, Castelijns JA. Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy.Ann Neurol 46: 79–87, 1999.PubMedGoogle Scholar
  82. 82.
    Pike GB, de Stefano N, Narayanan S, Francis GS, Antel JP, Arnold DL. Combined magnetization transfer and proton spec-troscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis.AJNR Am J Neuroradiol 20: 829–837, 1999.PubMedGoogle Scholar
  83. 83.
    Li BS, Regal J, Soher BJ, Mannon LJ, Grossman RI, Gonen O. Brain metabolite profiles of T1-hypointense lesions in relapsing-remitting multiple sclerosis.AJNR Am J Neuroradiol 24: 68–74, 2003.PubMedGoogle Scholar
  84. 84.
    Truyen L, van Waesberghe JH, van Walderveen MA, van Oosten BW, Polman CH, Hommes OR, et al. Accumulation of hypointense lesions (“black holes”) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis.Neurology 47: 1469–1476, 1996.PubMedGoogle Scholar
  85. 85.
    Enzinger C, Ropele S, Smith S, Strasser-Fuchs S, Poltrum B, Schmidt H, et al. Accelerated evolution of brain atrophy and “black holes” in MS patients with APOE-ε4.Ann Neurol 55: 563–569, 2004.PubMedGoogle Scholar
  86. 86.
    Wolinsky JS, Narayana PA, He R. Overview of treatment trials: early baseline clinical and MRI data of the PROMiSe trial. Primary progressive multiple sclerosis. Milano: Springer Italia, pp 47–61, 2002.Google Scholar
  87. 87.
    Gasperini C, Pozzilli C, Bastianello S, Giugni E, Horsfield MA, Koudriavtseva T, et al. Interferon-β-1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images.J Neurol Neurosurg Psychiatry 67: 579–584, 1999.PubMedGoogle Scholar
  88. 88.
    Simon JH, Lull J, Jacobs LD, Rudick RA, Cookfair DL, Herndon RM, et al. A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon β-1a. Multiple Sclerosis Collaborative Research Group.Neurology 55: 185–192, 2000.PubMedGoogle Scholar
  89. 89.
    Wolinsky JS, Comi G, Filippi M, Ladkani D, Kadosh S, Shifroni G. Copaxone’s effect on MRI-monitored disease in relapsing MS is reproducible and sustained.Neurology 59: 1284–1286, 2002.PubMedGoogle Scholar
  90. 90.
    Rocca MA, Mastronardo G, Rodegher M, Comi G, Filippi M. Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis.AJNR Am J Neuroradiol 20: 821–827, 1999.PubMedGoogle Scholar
  91. 91.
    Barkhof F, Van Waesberghe JH, Filippi M, Yuosry T, Miller DH, Hahn D, et al. T1 hypointense lesions in secondary progressive multiple sclerosis: effect of interferon β-1b treatment.Brain 124: 1396–1402, 2001.PubMedGoogle Scholar
  92. 92.
    Filippi M, Rovaris M, Rice GP, Sormani MP, Iannucci G, Giacomotti L, et al. The effect of cladribine on T(1) ‘black hole’ changes in progressive MS.J Neurol Sci 176: 42–44, 2000.PubMedGoogle Scholar
  93. 93.
    Paolillo A, Coles AJ, Molyneux PD, Gawne-Cain M, MacManus D, Barker GJ, et al. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath1H.Neurology 53: 751–757, 1999.PubMedGoogle Scholar
  94. 94.
    Dalton CM, Miszkiel KA, Barker GJ, MacManus DG, Pepple TI, Panzara M, et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis.J Neurol 251: 407–413, 2004.PubMedGoogle Scholar
  95. 95.
    Lin A, Ross BD, Harris K, Wong W. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making.NeuroRx 2: 197–214, 2005.PubMedGoogle Scholar
  96. 96.
    Narayana PA, Wolinsky JS, Jackson EF, McCarthy M. Proton MR spectroscopy of gadolinium-enhanced multiple sclerosis plaques.J Magn Reson Imaging 2: 263–270, 1992.PubMedGoogle Scholar
  97. 97.
    Mader I, Seeger U, Weissert R, Klose U, Naegele T, Melms A, et al. Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in acute multiple sclerosis.Brain 124: 953–961, 2001.PubMedGoogle Scholar
  98. 98.
    Helms G. Volume collection for edema in single-volume proton MR spectroscopy of contrast-enhancing multiple sclerosis lesions.Magn Reson Med 46: 256–263, 2001.PubMedGoogle Scholar
  99. 99.
    Bitsch A, Bruhn H, Vougioukas V, Stringaris A, Lassmann H, Frahm J, et al. Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy.AJNR: Am J Neuroradiol 20: 1619–1627, 1999.PubMedGoogle Scholar
  100. 100.
    Brex PA, Parker GJ, Leary SM, Molyneux PD, Barker GJ, Davie CA, et al. Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations.J Neurol Neurosurg Psychiatry 68: 627–632, 2000.PubMedGoogle Scholar
  101. 101.
    Bjartmar C, Trapp BD. Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences.Curr Opin Neurol 14: 271–278, 2001.PubMedGoogle Scholar
  102. 102.
    Kapeller P, McLean MA, Griffin CM, Chard D, Parker GJ, Barker GJ, et al. 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: 131–138, 2001.PubMedGoogle Scholar
  103. 103.
    Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH.1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis.J Neurol Neurosurg Psychiatry 63: 736–742, 1997.PubMedGoogle Scholar
  104. 104.
    Fu L, Matthews PM, De Stefano N, Worsley KJ, Narayanan S, Francis GS, et al. Imaging axonal damage of normal-appearing white matter in multiple sclerosis.Brain 121: 103–113, 1998.PubMedGoogle Scholar
  105. 105.
    De Stefano N, Narayanan S, Francis GS, Arnaoutelis R, Tartaglia MC, Antel JP, et al. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability.Arch Neurol 58: 65–70, 2001.PubMedGoogle Scholar
  106. 106.
    Gonen O, Catalaa I, Babb JS, Ge Y, Mannon LJ, Kolson DL, et al. Total brain N-acetylaspartate: a new measure of disease load in MS.Neurology 54: 15–19, 2000.PubMedGoogle Scholar
  107. 107.
    Brex PA, Gomez-Anson B, Parker GJ, Molyneux PD, Miszkiel KA, Barker GJ, et al. Proton MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis.J Neurol Sci 166: 16–22, 1999.PubMedGoogle Scholar
  108. 108.
    Cucurella MG, Rovira A, Rio J, Pedraza S, Tintore MM, Montalban X, et al. Proton magnetic resonance spectroscopy in primary and secondary progressive multiple sclerosis.NMR Biomed 13: 57–63, 2000.PubMedGoogle Scholar
  109. 109.
    Bjartmar C, Battistuta J, Terada N, Dupree E, Trapp BD. N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.Ann Neurol 51: 51–58, 2002.PubMedGoogle Scholar
  110. 110.
    Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis.Brain 122: 17–26, 1999.PubMedGoogle Scholar
  111. 111.
    Bakshi R, Ariyaratana S, Benedict RHB, Jacobs L. Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical and juxtacortical multiple sclerosis lesions.Arch Neurol 58: 742–748, 2001.PubMedGoogle Scholar
  112. 112.
    Inglese M, Liu S, Babb JS, Mannon LJ, Grossman RI, Gonen O. Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS.Neurology 63: 170–172, 2004.PubMedGoogle Scholar
  113. 113.
    Bermel RA, Innus MD, Tjoa CW, Bakshi R. Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study.Neuroreport 14: 335–339, 2003.PubMedGoogle Scholar
  114. 114.
    Tourbah A, Stievenart JL, Abanou A, Fontaine B, Cabanis EA, Lyon-Caen O. Correlating multiple MRI parameters with clinical features: an attempt to define a new strategy in multiple sclerosis.Neuroradiology 43: 712–720, 2001.PubMedGoogle Scholar
  115. 115.
    Suhy J, Rooney WD, Goodkin DE, Capizzano AA, Soher BJ, Maudsley AA, et al.1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS.Mult Scler 6: 148–155, 2000.PubMedGoogle Scholar
  116. 116.
    Narayana PA, Wolinsky JS, Rao SB, He R, Mehta M. Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis.Mult Scler 10(Suppl 1): S73-S78, 2004.PubMedGoogle Scholar
  117. 117.
    Pan JW, Krupp LB, Elkins LE, Coyle PK. Cognitive dysfunction lateralizes with NAA in multiple sclerosis.Appl Neuropsychol 8: 155–160, 2001.PubMedGoogle Scholar
  118. 118.
    Reddy H, Narayanan S, Arnoutelis R, Jenkinson M, Antel J, Matthews PM, et al. Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis.Brain 123: 2314–2320, 2000.PubMedGoogle Scholar
  119. 119.
    Arnold DL, Wolinsky JS, Matthews PM, Falini A. The use of magnetic resonance spectroscopy in the evaluation of the natural history of multiple sclerosis.J Neurol Neurosurg Psychiatry 649(Suppl 1): S94–101, 1998.Google Scholar
  120. 120.
    Narayanan S, De Stefano N, Francis GS, Arnaoutelis R, Caramanos Z, Collins DL, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon β-1b.J Neurol 248: 979–986, 2001.PubMedGoogle Scholar
  121. 121.
    Sarchielli P, Presciutti O, Tarducci R, Gobbi G, Alberti A, Pelliccioli GP, et al.1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study.J Neurol Neurosurg Psychiatry 64: 204–212, 1998.PubMedGoogle Scholar
  122. 122.
    Schubert F, Seifert F, Elster C, Link A, Walzel M, Mientus S, et al. Serial1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-β therapy on absolute metabolite concentrations.MAGMA 14: 213–222, 2002.PubMedGoogle Scholar
  123. 123.
    Parry A, Corkill R, Blamire AM, Palace J, Narayanan S, Arnold D, et al. β-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis.J Neurol 250: 171–178, 2003.PubMedGoogle Scholar
  124. 124.
    Inglese M, Ge Y, Filippi M, Falini A, Grossman RI, Gonen O. Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis.Neuroimage 21: 1825–1829, 2004.PubMedGoogle Scholar
  125. 125.
    Horsfield MA, Barker GJ, Barkhof F, Miller DH, Thompson AJ, Filippi M. Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis.J Magn Reson Imaging 17: 389–397, 2003.PubMedGoogle Scholar
  126. 126.
    Filippi M, Rocca MA. Magnetization transfer magnetic resonance imaging in the assessment of neurological diseases.J Neuroimaging 14: 303–313, 2004.PubMedGoogle Scholar
  127. 127.
    Dousset V, Grossman RI, Ramer KN, Schnall MD, Young LH, Gonzalez-Scarano F, et al. Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging.Radiology 182: 483–491, 1992.PubMedGoogle Scholar
  128. 128.
    van Buchem MA, McGowan JC, Kolson DL, Polansky M, Grossman RI. Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden.Magn Reson Med 36: 632–636, 1996.PubMedGoogle Scholar
  129. 129.
    van Waesberghe JH, van Walderveen MA, Castelijns JA, Scheltens P, Lycklama a Nijeholt GJ et al. Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR.AJNR Am J Neuroradiol 19: 675–683, 1998.PubMedGoogle Scholar
  130. 130.
    Lai HM, Davie CA, Gass A, Barker GJ, Webb S, Tofts PS, et al. Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis.J Neurol 244: 308–311, 1997.PubMedGoogle Scholar
  131. 131.
    Filippi M, Rocca MA, Martino G, Horsfield MA, Comi G. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis.Ann Neurol 43: 809–814, 1998.PubMedGoogle Scholar
  132. 132.
    Goodkin DE, Rooney WD, Sloan R, Bacchetti P, Gee L, Vermathen M, et al. A serial study of new MS lesions and the white matter from which they arise.Neurology 51: 1689–1697, 1998.PubMedGoogle Scholar
  133. 133.
    Silver NC, Lai M, Symms MR, Barker GJ, McDonald WI, Miller DH. Serial magnetization transfer imaging to characterize the early evolution of new MS lesions.Neurology 51: 758–764, 1998.PubMedGoogle Scholar
  134. 134.
    Pike GB, De Stefano N, Narayanan S, Worsley KJ, Pelletier D, Francis GS, et al. Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images.Radiology 215: 824–830, 2000.PubMedGoogle Scholar
  135. 135.
    Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S. Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis.Mult Scler 8: 479–484, 2002.PubMedGoogle Scholar
  136. 136.
    Miller DH, Thompson AJ, Filippi M. Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis.J Neurol 250: 1407–1419, 2003.PubMedGoogle Scholar
  137. 137.
    Ostuni JL, Richert ND, Lewis BK, Frank JA. Characterization of differences between multiple sclerosis and normal brain: a global magnetization transfer application.AJNR Am J Neuroradiol 20: 501–507, 1999.PubMedGoogle Scholar
  138. 138.
    Filippi M, Campi A, Dousset V, Baratti C, Martinelli V, Canal N, et al. A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis.Neurology 45: 478–482, 1995.PubMedGoogle Scholar
  139. 139.
    Audoin B, Ranjeva JP, Duong MV, Ibarrola D, Malikova I, Confort-Gouny S, et al. Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis.J Magn Reson Imaging 20: 765–771, 2004.PubMedGoogle Scholar
  140. 140.
    Lycklama a Nijeholt GJ, Castelijns JA, Lazeron RH, van Waesberghe JH, Polman CH, Uitdehaag BM, et al. Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability.J Neuroimaging 10: 67–72, 2000.PubMedGoogle Scholar
  141. 141.
    Thorpe JW, Barker GJ, Jones SJ, Moseley I, Losseff N, MacManus DG, et al. Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology.J Neurol Neurosurg Psychiatry 59: 487–492, 1995.PubMedGoogle Scholar
  142. 142.
    Filippi M, Iannucci G, Tortorella C, Minicucci L, Horsfield MA, Colombo B, et al. Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.Neurology 52: 588–594, 1999.PubMedGoogle Scholar
  143. 143.
    Rovaris M, Agosta F, Sormani MP, Inglese M, Martinelli V, Comi G, et al. Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.Brain 126: 2323–2332, 2003.PubMedGoogle Scholar
  144. 144.
    Santos AC, Narayanan S, de Stefano N, Tartaglia MC, Francis SJ, Arnaoutelis R, et al. Magnetization transfer can predict clinical evolution in patients with multiple sclerosis.J Neurol 249: 662–668, 2002.PubMedGoogle Scholar
  145. 145.
    Patel UJ, Grossman RI, Phillips MD, Udupa JK, McGowan JC, Miki Y, et al. Serial analysis of magnetization-transfer histograms and Expanded Disability Status Scale scores in patients with relapsing-remitting multiple sclerosis.AJNR Am J Neuroradiol 20: 1946–1950, 1999.PubMedGoogle Scholar
  146. 146.
    Cox D, Pelletier D, Genain C, Majumdar S, Lu Y, Nelson S, Mohr DC. The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients.Mult Scler 10: 626–629, 2004.PubMedGoogle Scholar
  147. 147.
    Zivadinov R, De Masi R, Nasuelli D, Bragadin LM, Ukmar M, Pozzi-Mucelli RS, et al. MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis.Neuroradiology 43: 272–278, 2001.PubMedGoogle Scholar
  148. 148.
    Richert ND, Frank JA. Magnetization transfer imaging to monitor clinical trials in multiple sclerosis.Neurology 53(5 Suppl 3): S29-S32, 1999.PubMedGoogle Scholar
  149. 149.
    Filippi M. Magnetization transfer MRI in multiple sclerosis and other central nervous system disorders.Eur J Neurol 10: 3–10, 2003.PubMedGoogle Scholar
  150. 150.
    Richert ND, Ostuni JL, Bash CN, Duyn JH, McFarland HF, Frank JA. Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon β-1b.AJNR Am J Neuroradiol 19: 1705–1713, 1998.PubMedGoogle Scholar
  151. 151.
    Filippi M, Inglese M, Rovaris M, Sormani MP, Horsfield P, Iannucci PG, et al. Magnetization transfer imaging to monitor the evolution of MS: a 1-year follow-up study.Neurology 55: 940–946, 2000.PubMedGoogle Scholar
  152. 152.
    Inglese M, van Waesberghe JH, Rovaris M, Beckmann K, Barkhof F, Hahn D, et al. The effect of interferon β-1b on quantities derived from MT MRI in secondary progressive MS.Neurology 60: 853–860, 2003.PubMedGoogle Scholar
  153. 153.
    Filippi M, Rocca MA, Pagani E, Iannucci G, Sormani MP, Fazekas F, et al. European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis.Arch Neurol 61: 1409–1412, 2004.PubMedGoogle Scholar
  154. 154.
    Kita M, Goodkin DE, Bacchetti P, Waubant E, Nelson SJ, Majumdar S. Magnetization transfer ratio in new MS lesions before and during therapy with IFN β-1a.Neurology 54: 1741–1745, 2000.PubMedGoogle Scholar
  155. 155.
    Frank JA, Richert N, Lewis B, Bash C, Howard T, Civil R, et al. A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients.Mult Scler 8: 24–29, 2002.PubMedGoogle Scholar
  156. 156.
    Miller DH, Barkhof F, Frank JA, Parker GJ, Thompson AJ. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance.Brain 125: 1676–1695, 2002.PubMedGoogle Scholar
  157. 157.
    Zivadinov R, Bakshi R. Role of MRI in multiple sclerosis II: brain and spinal cord atrophy.Front Biosci 9: 647–664, 2004.PubMedGoogle Scholar
  158. 158.
    Simon JH. From enhancing lesions to brain atrophy in relapsing MS.J Neuroimmunol 98: 7–15, 1999.PubMedGoogle Scholar
  159. 159.
    Minagar A, Toledo EG, Alexander JS, Kelley RE. Pathogenesis of brain and spinal cord atrophy in multiple sclerosis.J Neuroimaging 14(3 Suppl): 5S-10S, 2004.PubMedGoogle Scholar
  160. 160.
    Lassmann H. Mechanisms of demyelination and tissue damage in multiple sclerosis.Acta Neurol Belg 99: 6–10, 1999.PubMedGoogle Scholar
  161. 161.
    Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM. Thalamic neurodegeneration in multiple sclerosis.Ann Neurol 52: 650–653, 2002.PubMedGoogle Scholar
  162. 162.
    Filippi M, Rovaris M, Inglese M, Barkhof F, De Stefano N, Smith S, et al. Interferon β-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial.Lancet 364: 1489–1496, 2004.PubMedGoogle Scholar
  163. 163.
    Pelletier D, Garrison K, Henry R. Measurement of whole-brain atrophy in multiple sclerosis.J Neuroimaging 14(3 Suppl): 11S-19S, 2004.PubMedGoogle Scholar
  164. 164.
    Simon JH. Linear and regional measures of brain atrophy in multiple sclerosis. In: Brain and spinal cord atrophy in multiple sclerosis (Zivadinov R, Bakshi R, eds). Hauppauge: Nova Science, pp 15–27, 2004.Google Scholar
  165. 165.
    Lin X, Tench CR, Evangelou N, Jaspan T, Constantinescu CS. Measurement of spinal cord atrophy in multiple sclerosis.J Neuroimaging 14(3 Suppl): 20S-26S, 2004.PubMedGoogle Scholar
  166. 166.
    Benedict RH, Carone DA, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.J Neuroimaging 14(3 Suppl): 36S-45S, 2004.PubMedGoogle Scholar
  167. 167.
    Zivadinov R, Bakshi R. Central nervous system atrophy and clinical status in multiple sclerosis.J Neuroimaging 14(Suppl): 27S-35S, 2004.PubMedGoogle Scholar
  168. 168.
    Losseff NA, Wang L, Lai HM, Yoo DS, Gawne-Cain ML, McDonald WI, et al. Progressive cerebral atrophy in multiple sclerosis. A serial MRI study.Brain 119: 2009–2019, 1996.PubMedGoogle Scholar
  169. 169.
    Dastidar P, Heinonen T, Lehtimaki T, Ukkonen M, Peltola J, Erila T, Laasonen E, Elovaara I. Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis.J Neurol Sci 165: 36–42, 1999.PubMedGoogle Scholar
  170. 170.
    Bermel RA, Sharma J, Tjoa CW, Puli SR, Bakshi R. A semiautomated measure of whole-brain atrophy in multiple sclerosis.J Neurol Sci 208: 57–65, 2003.PubMedGoogle Scholar
  171. 171.
    Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC, et al. Eight-year follow-up study of brain atrophy in patients with MS.Neurology 59: 1412–1420, 2002.PubMedGoogle Scholar
  172. 172.
    Kidd D, Thorpe JW, Kendall BE, Barker GJ, Miller DH, McDonald WI, et al. MRI dynamics of brain and spinal cord in progressive multiple sclerosis.J Neurol Neurosurg Psychiatry 60: 15–19, 1996.PubMedGoogle Scholar
  173. 173.
    Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B, et al. One year follow up study of primary and transitional progressive multiple sclerosis.J Neurol Neurosurg Psychiatry 68: 713–718, 2000.PubMedGoogle Scholar
  174. 174.
    Ingle GT, Stevenson VL, Miller DH, Thompson AJ. Primary progressive multiple sclerosis: a 5-year clinical and MR study.Brain 126: 2528–2536, 2003.PubMedGoogle Scholar
  175. 175.
    Lin X, Tench CR, Turner B, Blumhardt LD, Constantinescu CS. Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon β-1a (Rebif) treatment trial.J Neurol Neurosurg Psychiatry 74: 1090–1094, 2003.PubMedGoogle Scholar
  176. 176.
    Rao SM, Glatt S, Hammeke TA, McQuillen MP, Khatri BO, Rhodes AM, et al. Chronic progressive multiple sclerosis. Relationship between cerebral ventricular size and neuropsychological impairment.Arch Neurol 42: 678–682, 1985.PubMedGoogle Scholar
  177. 177.
    Tsolaki M, Drevelegas A, Karachristianou S, Kapinas K, Divanoglou D, Routsonis K. Correlation of dementia, neuropsychological and MRI findings in multiple sclerosis.Dementia 5: 48–52, 1994.PubMedGoogle Scholar
  178. 178.
    Bermel RA, Bakshi R, Tjoa C, Puli SR, Jacobs L. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis.Arch Neurol 59: 275–280, 2002.PubMedGoogle Scholar
  179. 179.
    Christodoulou C, Krupp LB, Liang Z, Huang W, Melville P, Roque C, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients.Neurology 60: 1793–1798, 2003.PubMedGoogle Scholar
  180. 180.
    Hohol MJ, Guttmann CR, Orav J, Mackin GA, Kikinis R, Khoury SJ, et al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.Arch Neurol 54: 1018–1025, 1997.PubMedGoogle Scholar
  181. 181.
    Zivadinov R, Sepcic J, Nasuelli D, De Masi R, Bragadin LM, Tommasi MA, et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis.J Neurol Neurosurg Psychiatry 70: 773–780, 2001.PubMedGoogle Scholar
  182. 182.
    Benedict RHB, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R. Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden.Arch Neurol 61: 226–230, 2004.PubMedGoogle Scholar
  183. 183.
    Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, et al. Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment.Neurology 63: 89–93, 2004.PubMedGoogle Scholar
  184. 184.
    Benedict RHB, Sanfilipo M, Weinstock-Guttman B, Sharma J, Tjoa C, Bakshi R. The relationship of gray, white and total brain parenchymal fraction with cognitive performance in multiple sclerosis.Neurology 62(Suppl 5): A289, 2004.Google Scholar
  185. 185.
    Benedict RHB, Zivadinov R, Carone DA, Weinstock-Guttman B, Gaines J, Bakshi R. Temporal lobe atrophy predicts memory impairment in multiple sclerosis.AJNR Am J Neuroradiol, in press.Google Scholar
  186. 186.
    Rudick RA. Impact of disease-modifying therapies on brain and spinal cord atrophy in multiple sclerosis.J Neuroimaging 14(3 Suppl): 54S-64S, 2004.PubMedGoogle Scholar
  187. 187.
    Rovaris M, Filippi M. Treatment effects on MRI measures of central nervous system atrophy in multiple sclerosis. In: Brain and spinal cord atrophy in multiple sclerosis (Zivadinov R, Bakshi R, eds), pp 175–190. Hauppauge: Nova Science, 2004.Google Scholar
  188. 188.
    Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group.Neurology 53: 1698–1704, 1999.PubMedGoogle Scholar
  189. 189.
    Jones CK, Riddehough A, Li DKB, Zhao G, Paty DW, PRISMS Study Group, et al. MRI cerebral atrophy in relapsing-remitting MS: results from the PRISMS trial.Neurology 56(Suppl 3): A379, 2001.Google Scholar
  190. 190.
    Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi M, et al. The effect of interferon β-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon β-1b in secondary progressive multiple sclerosis.Brain 123: 2256–2263, 2000.PubMedGoogle Scholar
  191. 191.
    Frank JA, Richert N, Bash C, Stone L, Calabresi PA, Lewis B, Stone R, Howard T, McFarland HF. Interferon-β-1b slows progression of atrophy in RRMS: three-year follow-up in NAb- and NAb+ patients.Neurology 62: 719–725, 2004.PubMedGoogle Scholar
  192. 192.
    Ge Y, Grossman RI, Udupa JK, Fulton J, Constantinescu CS, Gonzales-Scarano F, et al. Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.Neurology 54: 813–817, 2000.PubMedGoogle Scholar
  193. 193.
    Wolinsky JS, Narayana PA, Johnson KP; Multiple Sclerosis Study Group and the MRI Analysis Center. United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates.Mult Scler 7: 33–41, 2001.PubMedGoogle Scholar
  194. 194.
    Rovaris M, Comi G, Rocca MA, Wolinsky JS, Filippi M; European/Canadian Glatiramer Acetate Study Group. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications.Brain 124: 1803–1812, 2001.PubMedGoogle Scholar
  195. 195.
    Sormani MP, Rovaris M, Valsasina P, Wolinsky JS, Comi G, Filippi M. Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis.Neurology 62: 1432–1434, 2004.PubMedGoogle Scholar
  196. 196.
    Zivadinov R, Rudick RA, De Masi R, Nasuelli D, Ukmar M, Pozzi-Mucelli RS, et al. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS.Neurology 7: 1239–1247, 2001.Google Scholar
  197. 197.
    Gasperini C. Whole-brain atrophy measurement and short-term brain volume changes. In: Brain and spinal cord atrophy in multiple sclerosis (Zivadinov R, Bakshi R, eds). Hauppauge: Nova Science, pp 29–38, 2004.Google Scholar
  198. 198.
    Quint DJ. Hyperintense disks on T1-weighted MR images: are they important?Radiology 195: 325–326, 1995.PubMedGoogle Scholar
  199. 199.
    Powell T, Sussman JG, Davies-Jones GA. MR imaging in acute multiple sclerosis: ringlike appearance in plaques suggesting the presence of paramagnetic free radicals.AJNR Am J Neuroradiol 13: 1544–1546, 1992.PubMedGoogle Scholar
  200. 200.
    Terada H, Barkovich AJ, Edwards MS, Ciricillo SM. Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1.AJNR Am J Neuroradiol 17: 755–760, 1996.PubMedGoogle Scholar
  201. 201.
    Bakshi R, Suri S, Benedict RHB, Weinstock-Guttman B, Bermel RA, Tjoa CW, et al. Bright lesions in the brain on non-contrast T1-weighted MRI scans (T1 shortening) in multiple sclerosis.Neurology 58(Suppl 3): A208-A209, 2002.Google Scholar
  202. 202.
    Guttmann CRG, Ahn SS, Hsu L, Kikinis R, Jolesz FA. The evolution of multiple sclerosis lesions on serial MR.AJNR Am J Neuroradiol 16: 1481–1491, 1995.PubMedGoogle Scholar
  203. 203.
    Drayer BP, Burger P, Hurwitz B, Dawson D, Cain J, Leong J, et al. Magnetic resonance imaging in multiple sclerosis: decreased signal in thalamus and putamen.Ann Neurol 22: 546–550, 1987.PubMedGoogle Scholar
  204. 204.
    Bakshi R, Shaikh ZA, Janardhan V. MRI T2 shortening (‘black T2’) in multiple sclerosis: frequency, location, and clinical correlation.Neuroreport 11: 15–21, 2000.PubMedGoogle Scholar
  205. 205.
    Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CW, et al. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study.Arch Neurol 59: 62–68, 2002.PubMedGoogle Scholar
  206. 206.
    Bakshi R, Dmochowski J, Shaikh ZA, Jacobs L. Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients.J Neurol Sci 185: 19–26, 2001.PubMedGoogle Scholar
  207. 207.
    Bermel RA, Puli SR, Rudick RA, Weinstock-Guttman B, Fisher E, Munschauer FE, Bakshi R. Gray matter MRI T2 hypointensity predicts longitudinal brain atrophy in MS.Arch Neurol, in press.Google Scholar
  208. 208.
    Schenck JF, Zimmerman EA. High-field magnetic resonance imaging of brain iron: birth of a biomarker?NMR Biomed 17: 433–445, 2004.PubMedGoogle Scholar
  209. 209.
    Gutteridge JMC. Iron and oxygen radicals in brain.Ann Neurol 32: 16–21, 1992.Google Scholar
  210. 210.
    Levine SM, Chakrabarty A. The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis.Ann NY Acad Sci 1012: 252–266, 2004.PubMedGoogle Scholar
  211. 211.
    Weilbach FX, Chan A, Toyka KV, Gold R. The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in experimental autoimmune encephalomyelitis.Clin Exp Immunol 135: 49–55, 2004.PubMedGoogle Scholar
  212. 212.
    Bammer R, Skare S, Newbould R, Liu C, Thijs V, Ropele S, Clayton DB, Krueger G, Moseley ME, Glover GH. Foundations of advanced magnetic resonance imaging.NeuroRx 2: 167–196, 2005.PubMedGoogle Scholar
  213. 213.
    Filippi M, Inglese M. Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis.J Neurol Sci 186: S37-S43, 2001.PubMedGoogle Scholar
  214. 214.
    Bammer R, Fazekas F. Diffusion imaging in multiple sclerosis.Neuroimaging Clin N Am 12: 71–106, 2002.PubMedGoogle Scholar
  215. 215.
    Droogan AG, Clark CA, Werring DJ, Barker GJ, McDonald WI, Miller DH. Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging.Magn Reson Imaging 17: 653–661, 1999.PubMedGoogle Scholar
  216. 216.
    Horsfield MA, Lai M, Webb SL, Barker GJ, Tofts PS, Turner R, et al. Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance.Magn Reson Med 36: 393–400, 1996.PubMedGoogle Scholar
  217. 217.
    Bammer R, Augustin M, Strasser-Fuchs S, Seifert T, Kapeller P, Stollberger R, et al. Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis.Magn Reson Med 44: 583–591, 2000.PubMedGoogle Scholar
  218. 218.
    Werring DJ, Brassat D, Droogan AG, Clark CA, Symms MR, Barker GJ, et al. The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study.Brain 123: 1667–1676, 2000.PubMedGoogle Scholar
  219. 219.
    Guo AC, MacFall JR, Provenzale JM. Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal-appearing white matter.Radiology 222: 729–736, 2002.PubMedGoogle Scholar
  220. 220.
    Roychowdhury S, Maldjian JA, Grossman RI. Multiple sclerosis: comparison of trace apparent diffusion coefficients with MR enhancement pattern of lesions.AJNR Am J Neuroradiol 21: 869–874, 2000.PubMedGoogle Scholar
  221. 221.
    Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, et al. Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations.Neurology 56: 926–933, 2001.PubMedGoogle Scholar
  222. 222.
    Rocca MA, Cercignani M, Iannucci G, Comi G, Filippi M. Weekly diffusion-weighted imaging of normal-appearing white matter in MS.Neurology 55: 882–884, 2000.PubMedGoogle Scholar
  223. 223.
    Coombs BD, Best A, Brown MS, Miller DE, Corboy J, Baier M, et al. Multiple sclerosis pathology in the normal and abnormal appearing white matter of the corpus callosum by diffusion tensor imaging.Mult Scler 10: 392–397, 2004.PubMedGoogle Scholar
  224. 224.
    Cassol E, Ranjeva JP, Ibanola D, Mekies C, Manelfe C, Clanet M, et al. Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter.Mult Scler 10: 188–196, 2004.PubMedGoogle Scholar
  225. 225.
    Schmierer K, Altmann DR, Kassim N, Kitzler H, Kerskens CM, Doege CA, et al. A. Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study.Mult Scler 10: 182–187, 2004.PubMedGoogle Scholar
  226. 226.
    Fabiano AJ, Sharma J, Weinstock-Guttman B, Benedict RH, Zivadinov R, Bakshi R. Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study.J Neuroimaging 13: 307–314, 2003.PubMedGoogle Scholar
  227. 227.
    Rovaris M, Iannucci G, Falautano M, Possa F, Martinelli V, Comi G, et al. Cognitive dysfunction in patients with mildly disabling relapsing-remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging.J Neurol Sci 195: 103–109, 2002.PubMedGoogle Scholar
  228. 228.
    Wilson M, Tench CR, Morgan PS, Blumhardt LD. Pyramidal tract mapping by diffusion tensor magnetic resonance imaging in multiple sclerosis: improving conelations with disability.J Neurol Neurosurg Psychiatry 74: 203–207, 2003.PubMedGoogle Scholar
  229. 229.
    Caramia F, Pantano P, Di Legge S, Piattella MC, Lenzi D, Paolillo A, et al. A longitudinal study of MR diffusion changes in NAWM of patients with early multiple sclerosis.Magn Res Imag 20: 383–388, 2002.Google Scholar
  230. 230.
    Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI.J Neurology 249: 875–883, 2002.Google Scholar
  231. 231.
    Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G. Diffusion tensor magnetic resonance imaging in multiple sclerosis.Neurology 56: 304–311, 2001.PubMedGoogle Scholar
  232. 232.
    Griffin CM, Chard DT, Ciccarelli O, Kapoor B, Barker GJ, Thompson AI, Miller DH. Diffusion tensor imaging in early relapsing-remitting multiple sclerosis.Multiple Sclerosis 7: 290–297, 2001.PubMedGoogle Scholar
  233. 233.
    Brooks DJ. Positron emission tomography and single-photon emission computed tomography in central nervous system drug development.NeuroRx 2: 226–236, 2005.PubMedGoogle Scholar
  234. 234.
    Devous MD Sr. Single-photon emission computed tomography in neurotherapeutics.NeuroRx 2: 237–249, 2005.PubMedGoogle Scholar
  235. 235.
    Sabatini U, Pozzilli C, Pantano P, Koudriavtseva T, Padovani A, Millefiorini E, et al. Involvement of the limbic system in multiple sclerosis patients with depressive disorders.Biol Psychiatry 39: 970–975, 1996.PubMedGoogle Scholar
  236. 236.
    Paulesu E, Perani D, Fazio F, Comi G, Pozzilli C, Martinelli V, et al. Functional basis of memory impairment in multiple sclerosis: a [18F]FDG PET study.Neuroimage 4: 87–96, 1996.PubMedGoogle Scholar
  237. 237.
    Bakshi R, Miletich RS, Kinkel PR, Emmet ML, Kinkel WR. High-resolution fluorodeoxyglucose positron emission tomography shows both global and regional cerebral hypometabolism in multiple sclerosis.J Neuroimaging 8: 228–234, 1998.PubMedGoogle Scholar
  238. 238.
    Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S. Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study.Ann Nucl Med 12: 89–94, 1998.PubMedGoogle Scholar
  239. 239.
    Blinkenberg M, Jensen CV, Holm S, Paulson OB, Sorensen PS. A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS.Neurology 53: 149–153, 1999.PubMedGoogle Scholar
  240. 240.
    Blinkenberg M, Rune K, Jensen CV, Ravnborg M, Kyllingsbaek S, Holm S, et al. Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS.Neurology 54: 558–564, 2000.PubMedGoogle Scholar
  241. 241.
    Santa Maria MP, Benedict RHB, Bakshi R, Coad ML, Wack D, Burkard R, et al. Functional imaging during covert auditory attention in multiple sclerosis.J Neurol Sci 218: 9–15, 2004.Google Scholar
  242. 242.
    Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W, et al. Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study.Neurology 48: 1566–1571, 1997.PubMedGoogle Scholar
  243. 243.
    Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.Brain 123: 2321–2337, 2000.PubMedGoogle Scholar
  244. 244.
    Debruyne JC, Versijpt J, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, et al. PET visualization of microglia in multiple sclerosis patients using [11C]PK11195.Eur J Neurol 10: 257–264, 2003.PubMedGoogle Scholar
  245. 245.
    Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, Antel JP. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis.J Neurosci Res 50: 345–353, 1997.PubMedGoogle Scholar
  246. 246.
    Yousry TA, Berry I, Filippi M. Functional magnetic resonance imaging in multiple sclerosis.J Neurol Neurosurg Psychiatry 64(Suppl 1): S85-S87, 1998.PubMedGoogle Scholar
  247. 247.
    Gareau PJ, Gati JS, Menon RS, Lee D, Rice G, Mitchell JR, et al. Reduced visual evoked responses in multiple sclerosis patients with optic neuritis: comparison of functional magnetic resonance imaging and visual evoked potentials.Mult Scler 5: 161–164, 1999.PubMedGoogle Scholar
  248. 248.
    Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson M, Smith S, et al. The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.Ann Neurol 47: 606–613, 2000.PubMedGoogle Scholar
  249. 249.
    Pantano P, Iannetti GD, Caramia F, Mainero C, Di Legge S, Bozzao L, et al. Cortical motor reorganization after a single clinical attack of multiple sclerosis.Brain 125: 1607–1615, 2002.PubMedGoogle Scholar
  250. 250.
    Parry AM, Scott RB, Palace J, Smith S, Matthews PM. Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine.Brain 126: 2750–2760, 2003.PubMedGoogle Scholar
  251. 251.
    Penner IK, Rausch M, Kappos L, Opwis K, Radu EW. Analysis of impairment related functional architecture in MS patients during performance of different attention tasks.J Neurol 250: 461–472, 2003.PubMedGoogle Scholar
  252. 252.
    Reddy H, Narayanan S, Woolrich M, Mitsumori T, Lapierre Y, Arnold DL, et al. Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability.Brain 125: 2646–2657, 2002.PubMedGoogle Scholar
  253. 253.
    Staffen W, Mail- A, Zauner H, Unterrainer J, Niederhofer H, Kutzelnigg A, et al. Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task.Brain 125: 1275–1282, 2002.PubMedGoogle Scholar
  254. 254.
    Sweet LH, Rao SM, Primeau M, Mayer AR, Cohen RA. Functional magnetic resonance imaging of working memory among multiple sclerosis patients.J Neuroimaging 14: 150–157, 2004.PubMedGoogle Scholar
  255. 255.
    Filippi M, Rocca MA, Mezzapesa DM, Falini A, Colombo B, Scotti G, et al. A functional MRI study of cortical activations associated with object manipulation in patients with MS.Neuroimage 21: 1147–1154, 2004.PubMedGoogle Scholar
  256. 256.
    Filippi M, Rocca MA, Mezzapesa DM, Ghezzi A, Falini A, Martinelli V, et al. Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.Hum Brain Mapp 21: 108–117, 2004.PubMedGoogle Scholar
  257. 257.
    Mackowiak PA, Siegel E, Wasserman SS, Cameron E, Nessaiver MS, Bever CT. Effects of IFN-β on human cerebral blood flow distribution.J Interferon Cytokine Res 18: 393–397, 1998.PubMedGoogle Scholar
  258. 258.
    Pirko I, Fricke ST, Johnson AJ, Rodriguez M, Macura SI. Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals.NeuroRx 2: 250–264, 2005.PubMedGoogle Scholar
  259. 259.
    Tortorella C, Viti B, Bozzali M, Sormani MP, Rizzo G, Gilardi MF, Comi G, Filippi M. A magnetization transfer histogram study of normal-appearing brain tissue in MS.Neurology, 54: 186–193, 2000.PubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2005

Authors and Affiliations

  • Rohit Bakshi
    • 1
    • 4
  • Alireza Minagar
    • 2
  • Zeenat Jaisani
    • 1
  • Jerry S. Wolinsky
    • 3
  1. 1.Departments of Neurology and Radiology, Partners MS Center, Center for Neurological ImagingBrigham and Women’s Hospital, Harvard Medical SchoolBoston
  2. 2.Department of NeurologyLouisiana State University Health Sciences CenterShreveport
  3. 3.Department of NeurologyUniversity of Texas Health Science Center at HoustonHouston
  4. 4.FAAN Brigham & Women’s Hospital Harvard Medical SchoolBoston

Personalised recommendations