European Radiology

, Volume 19, Issue 8, pp 2066–2074

MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

  • J. Bellmann-Strobl
  • H. Stiepani
  • J. Wuerfel
  • G. Bohner
  • F. Paul
  • C. Warmuth
  • O. Aktas
  • K. P. Wandinger
  • F. Zipp
  • R. Klingebiel
Neuro

Abstract

The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0 ± 7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon β-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p < 0.05) and correlated to the MSFC score (r = 0.476, p < 0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p < 0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects.

Keywords

Multiple sclerosis MR spectroscopy Magnetisation transfer imaging White matter 

References

  1. 1.
    Pugliatti M, Sotgiu S, Rosati G (2002) The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 104(3):182–191PubMedCrossRefGoogle Scholar
  2. 2.
    Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria". Ann Neurol 58(6):840–846PubMedCrossRefGoogle Scholar
  3. 3.
    Filippi M, Rovaris M (2000) Magnetisation transfer imaging in multiple sclerosis. J Neurovirol 6(Suppl 2):S115–S1120PubMedGoogle Scholar
  4. 4.
    Tedeschi G, Bonavita S, McFarland HF et al (2002) Proton MR spectroscopic imaging in multiple sclerosis. Neuroradiology 44(1):37–42PubMedCrossRefGoogle Scholar
  5. 5.
    Inglese M, Rovaris M, Bianchi S et al (2001) 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. J Neurol Neurosurg Psychiatry 70(4):444–449PubMedCrossRefGoogle Scholar
  6. 6.
    Narayana PA (2005) Magnetic resonance spectroscopy in the monitoring of multiple sclerosis. J Neuroimaging 15(4 Suppl):46S–57SPubMedCrossRefGoogle Scholar
  7. 7.
    Horsfield MA (2005) Magnetization transfer imaging in multiple sclerosis. J Neuroimaging 15(4 Suppl):58S–67SPubMedCrossRefGoogle Scholar
  8. 8.
    Pascual-Lozano A, Martinez-Bisbal M, Bosca I et al (2006) Axonal damage and inflammation in early multiple sclerosis: effects of subcutaneously interferon-beta-1a treatment. Mult Scler 12:S186Google Scholar
  9. 9.
    Narayanan S, De Stefano N, Francis GS et al (2001) Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 248(11):979–986PubMedCrossRefGoogle Scholar
  10. 10.
    Sarchielli P, Presciutti O, Tarducci R et al (1998) 1H-MRS in patients with multiple sclerosis undergoing treatment with interferon beta-1a: results of a preliminary study. J Neurol Neurosurg Psychiatry 64(2):204–212PubMedCrossRefGoogle Scholar
  11. 11.
    Parry A, Corkill R, Blamire AM et al (2003) Beta-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis. J Neurol 250(2):171–178PubMedCrossRefGoogle Scholar
  12. 12.
    Richert ND, Ostuni JL, Bash CN et al (1998) Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b. AJNR Am J Neuroradiol 19(9):1705–1713PubMedGoogle Scholar
  13. 13.
    Kita M, Goodkin DE, Bacchetti P et al (2000) Magnetization transfer ratio in new MS lesions before and during therapy with IFNbeta-1a. Neurology 54(9):1741–1745Google Scholar
  14. 14.
    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(1):121–127PubMedCrossRefGoogle Scholar
  15. 15.
    Cutter GR, Baier ML, Rudick RA et al (1999) Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 122:871–882PubMedCrossRefGoogle Scholar
  16. 16.
    Rovaris M, Filippi M, Minicucci L et al (2000) Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. AJNR Am J Neuroradiol 21(2):402–408PubMedGoogle Scholar
  17. 17.
    Bakshi R, Thompson AJ, Rocca MA et al (2008) MRI in multiple sclerosis: current status and future prospects. Lancet Neurol 7(7):615–625PubMedCrossRefGoogle Scholar
  18. 18.
    Zivadinov R, Stosic M, Cox J et al (2008) The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome. J Neurol 255(0):61–74PubMedCrossRefGoogle Scholar
  19. 19.
    Chen JT, Collins DL, Atkins HL et al (2008) Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions. Ann Neurol 63(2):254–262PubMedCrossRefGoogle Scholar
  20. 20.
    Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45(1):37–45PubMedCrossRefGoogle Scholar
  21. 21.
    Zivadinov R (2007) Can imaging techniques measure neuroprotection and remyelination in multiple sclerosis? Neurology 68(22 Suppl 3):S72–S82PubMedCrossRefGoogle Scholar
  22. 22.
    Giacomini PS, Arnold DL (2008) Non-conventional MRI techniques for measuring neuroprotection, repair and plasticity in multiple sclerosis. Curr Opin Neurol 21(3):272–277PubMedCrossRefGoogle Scholar
  23. 23.
    Rovira A, Leon A (2008) MR in the diagnosis and monitoring of multiple sclerosis: An overview. Eur J Radiol 67(3):409–414PubMedCrossRefGoogle Scholar
  24. 24.
    Inglese M (2006) Multiple sclerosis: new insights and trends. AJNR Am J Neuroradiol 27(5):954–957PubMedGoogle Scholar
  25. 25.
    Khaleeli Z, Sastre-Garriga J, Ciccarelli O et al (2007) Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 78(10):1076–1082PubMedCrossRefGoogle Scholar
  26. 26.
    Wattjes MP, Harzheim M, Lutterbey GG et al (2008) Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Neuroradiology 50(2):123–129PubMedCrossRefGoogle Scholar
  27. 27.
    De Stefano N, Guidi L, Stromillo ML et al (2003) Imaging neuronal and axonal degeneration in multiple sclerosis. Neurol Sci 24(Suppl 5):S283–S286PubMedCrossRefGoogle Scholar
  28. 28.
    Filippi M, Rocca MA, Comi G (2003) The use of quantitative magnetic-resonance-based techniques to monitor the evolution of multiple sclerosis. Lancet Neurol 2(6):337–346PubMedCrossRefGoogle Scholar
  29. 29.
    Pascual AM, Martinez-Bisbal MC, Bosca I et al (2007) Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis. Neurology 69(1):63–67PubMedCrossRefGoogle Scholar
  30. 30.
    Inglese M, Li BS, Rusinek H et al (2003) Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med 50(1):190–195PubMedCrossRefGoogle Scholar
  31. 31.
    Wattjes MP, Harzheim M, Lutterbey GG et al (2008) High field MR imaging and (1)H-MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis: correlation between metabolic alterations and diagnostic MR imaging criteria. J Neurol 255(1):56–63PubMedCrossRefGoogle Scholar
  32. 32.
    Rieckmann P (2005) Neurodegeneration and clinical relevance for early treatment in multiple sclerosis. Int MS J 12(2):42–51PubMedGoogle Scholar
  33. 33.
    Neema M, Stankiewicz J, Arora A et al (2007) MRI in multiple sclerosis: what’s inside the toolbox? Neurotherapeutics 4(4):602–617PubMedCrossRefGoogle Scholar
  34. 34.
    Adalsteinsson E, Langer-Gould A, Homer RJ et al (2003) Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 24(10):1941–1945PubMedGoogle Scholar
  35. 35.
    Jacobs LD, Cookfair DL, Rudick RA et al (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39(3):285–294PubMedCrossRefGoogle Scholar
  36. 36.
    PRISMS Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet Neurol 352(9139):1498–1504Google Scholar
  37. 37.
    Kappos L, Freedman MS, Polman CH et al (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370(9585):389–397PubMedCrossRefGoogle Scholar
  38. 38.
    Chen JT, Kuhlmann T, Jansen GH et al (2007) Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion. Neuroimage 36(4):1152–1158PubMedCrossRefGoogle Scholar
  39. 39.
    Deloire MS, Salort E, Bonnet M et al (2005) Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76(4):519–526PubMedCrossRefGoogle Scholar
  40. 40.
    Vrenken H, Pouwels PJ, Ropele S et al (2007) Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease. Mult Scler 13(6):708–716PubMedCrossRefGoogle Scholar
  41. 41.
    Laule C, Vavasour IM, Whittall KP et al (2003) Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis. J Neurol 250(8):924–931PubMedCrossRefGoogle Scholar
  42. 42.
    Horakova D, Cox JL, Havrdova E et al (2008) Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years. A case control study. J Neurol Neurosurg Psychiatry 79(4):407–414PubMedCrossRefGoogle Scholar
  43. 43.
    Davies GR, Ramio-Torrenta L, Hadjiprocopis A (2004) Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 75(7):998–1002PubMedCrossRefGoogle Scholar
  44. 44.
    Oreja-Guevara C, Charil A, Caputo D et al (2006) Magnetization transfer magnetic resonance imaging and clinical changes in patients with relapsing-remitting multiple sclerosis. Arch Neurol 63(5):736–440PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2009

Authors and Affiliations

  • J. Bellmann-Strobl
    • 2
  • H. Stiepani
    • 1
  • J. Wuerfel
    • 2
    • 5
  • G. Bohner
    • 1
  • F. Paul
    • 2
  • C. Warmuth
    • 3
  • O. Aktas
    • 2
  • K. P. Wandinger
    • 4
  • F. Zipp
    • 2
  • R. Klingebiel
    • 1
  1. 1.Department of NeuroradiologyCharité—University Medicine BerlinBerlinGermany
  2. 2.Cecilie Vogt Clinic for NeurologyCharité—University Medicine Berlin and Max Delbrueck Center for Molecular MedicineBerlinGermany
  3. 3.Department of RadiologyCharité—University Medicine BerlinBerlinGermany
  4. 4.Department of NeurologyCharité—University Medicine BerlinBerlinGermany
  5. 5.Institute of Neuroradiology, Campus LuebeckUniversity Schleswig-HolsteinKielGermany

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