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Proton MR Spectroscopy

  • N. De Stefano
Part of the Topics in Neuroscience book series (TOPNEURO)

Abstract

In the last few years, there has been an increased appreciation of the apparently primary role of neuronal and axonal injury in the pathogenesis of multiple sclerosis (MS) [1, 2]. This has been driven to a significant degree by the results of proton magnetic resonance (MR) spectroscopy (1H-MRS) studies, which have emphasized that substantial neuroaxonal damage occurs inside the demyelinating lesions as well as in the normal-appearing white matter (NAWM) and gray matter (GM) of the brain of patients with MS [2, 3]. All this has been confirmed pathologically [1, 4, 5] and has led to a reconsideration of the role of axonal damage in MS [6].

Keywords

Multiple Sclerosis Axonal Injury Multiple Sclerosis Lesion Axonal Damage Magnetic Resonance Spectroscopy Study 
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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References

  1. 1.
    Trapp BD, Peterson J, Ransohoff RM et al (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285PubMedCrossRefGoogle Scholar
  2. 2.
    Matthews PM, De Stefano N, Narayanan S et al (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol 18:327–336PubMedGoogle Scholar
  3. 3.
    Wolinsky JS, Narayana PA (2002) Magnetic resonance spectroscopy in multiple sclerosis: window into the diseased brain. Curr Opin Neurol 15:247–251PubMedCrossRefGoogle 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.
    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
  6. 6.
    Trapp BD, Ransohoff RM, Fisher E, Rudick RA (1999) Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist 5:48–57CrossRefGoogle Scholar
  7. 7.
    Waxman SG (2000) Multiple sclerosis as a neuronal disease. Arch Neurol 57:22–24PubMedCrossRefGoogle Scholar
  8. 8.
    Trapp BD (2004) Pathogenesis of multiple sclerosis: the eyes only see what the mind is prepared to comprehend. Ann Neurol 55:455–457PubMedCrossRefGoogle Scholar
  9. 9.
    Stys PK (2004) Axonal degeneration in multiple sclerosis: is it time for neuroprotective strategies? Ann Neurol 55:601–603PubMedCrossRefGoogle Scholar
  10. 10.
    Gordon RE, Hanley PE, Shaw D et al (1980) Localization of metabolites in animals using 31P topical magnetic resonance. Nature 287:736–738PubMedCrossRefGoogle Scholar
  11. 11.
    Gonen O, Viswanathan AK, Catalaa I et al (1998) Total brain N-acetylaspartate concentration in normal, age-grouped females: quantitation with non-echo proton NMR spectroscopy. Magn Reson Med 40:684–689PubMedCrossRefGoogle Scholar
  12. 12.
    Arnold DL, Matthews PM (1996) Practical aspects of clinical applications of MRS in the brain. In: Young IR, Charles HC (eds) MR spectroscopy: clinical applications and techniques. Martin Dunitz, London, pp 139–159Google Scholar
  13. 13.
    Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264PubMedCrossRefGoogle Scholar
  14. 14.
    Davie CA, Hawkins CP, Barker GJ et al (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 117:49–58PubMedCrossRefGoogle Scholar
  15. 15.
    De Stefano N, Matthews PM, Antel JP et al (1995) Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol 38:901–909PubMedCrossRefGoogle Scholar
  16. 16.
    Narayana PA, Doyle TJ, Lai D, Wolinsky JS (1998) Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 43:56–71PubMedCrossRefGoogle Scholar
  17. 17.
    Srinivasan R, Sailasuta N, Hurd R et al (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 128:1016–1025PubMedCrossRefGoogle Scholar
  18. 18.
    Kapeller P, Brex PA, Chard D et al (2002) Quantitative 1H MRS imaging 14 years after presenting with a clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 8:207–210PubMedCrossRefGoogle Scholar
  19. 19.
    De Stefano N, Matthews PM, Arnold DL (1995) Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 34:721–727PubMedCrossRefGoogle Scholar
  20. 20.
    Husted CA, Goodin DS, Hugg JW et al (1994) Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging. Ann Neurol 36:157–165PubMedCrossRefGoogle Scholar
  21. 21.
    Narayanan S, Fu L, Pioro E et al (1997) Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions. Ann Neurol 41:385–391PubMedCrossRefGoogle Scholar
  22. 22.
    Davie CA, Barker GJ, Thompson AJ et al (1997) 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal-appearing white matter in multiple sclerosis. J Neurol Neurosurg Psychiat 63:736–742PubMedGoogle Scholar
  23. 23.
    Fu L, Matthews PM, De Stefano N et al (1998) Imaging axonal damage of normalappearing white matter in multiple sclerosis. Brain 121:103–113PubMedCrossRefGoogle Scholar
  24. 24.
    Sarchielli P, Presciutti O, Pelliccioli GP et al (1999) Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients. Brain 122:513–521PubMedCrossRefGoogle Scholar
  25. 25.
    Miller DH, Austin SJ, Connelly A et al (1991) Proton magnetic resonance spectroscopy of an acute and chronic lesion in multiple sclerosis. Lancet 337:58–59PubMedCrossRefGoogle Scholar
  26. 26.
    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
  27. 27.
    De Stefano N, Narayanan S, Francis SJ et al (2002) Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability. Arch Neurol 59:1565–1571PubMedCrossRefGoogle Scholar
  28. 28.
    Wolinsky JS, Narayana PA, Fenstermacher MJ (1990) Proton magnetic resonance spectroscopy in multiple sclerosis. Neurology 40:1764–1769PubMedGoogle Scholar
  29. 29.
    Bruhn H, Frahm J, Merboldt KD et al (1992) Multiple sclerosis in children: cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo. Ann Neurol 32:140–150PubMedCrossRefGoogle Scholar
  30. 30.
    Fernando KT, McLean MA, Chard DT et al (2004) Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis. Brain 127:1361–1369PubMedCrossRefGoogle Scholar
  31. 31.
    Chard DT, Griffin CM, McLean MA et al (2002) Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis. Brain 125:2342–2352PubMedCrossRefGoogle Scholar
  32. 32.
    Tartaglia MC, Narayanan S, De Stefano N et al (2002) Choline is increased in prelesional normal-appearing white matter in multiple sclerosis. J Neurol 249:1382–1390PubMedCrossRefGoogle Scholar
  33. 33.
    Filippi M, Rocca MA, Martino G et al (1998) Magnetization transfer changes in the normal-appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann Neurol 43:809–814PubMedCrossRefGoogle Scholar
  34. 34.
    Caramanos Z, Narayanan S, Arnold DL (2005) 1H-MRS quantification of tNA and tCr in patients with multiple sclerosis: a meta-analytic review. Brain 128:2483–2506PubMedCrossRefGoogle Scholar
  35. 35.
    De Stefano N, Bartolozzi ML, Guidi L et al (2005) Magnetic resonance spectroscopy as a measure of brain damage in multiple sclerosis. J Neurol Sci 233:203–208PubMedCrossRefGoogle Scholar
  36. 36.
    Wylezinska M, Cifelli A, Jezzard P et al (2003) Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 60:1949–1954PubMedGoogle Scholar
  37. 37.
    Inglese M, Liu S, Babb JS et al (2004) Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS. Neurology 63:170–172PubMedGoogle Scholar
  38. 38.
    Geurts JJ, Reuling IE, Vrenken H. et al (2006) MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magn Reson Med 55:478–483PubMedCrossRefGoogle Scholar
  39. 39.
    Cifelli A, Arridge M, Jezzard P et al (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653PubMedCrossRefGoogle Scholar
  40. 40.
    Birken DL, Oldendorf WH (1989) N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 13:23–31PubMedCrossRefGoogle Scholar
  41. 41.
    Baslow MH (2003) N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res 28:941–953PubMedCrossRefGoogle Scholar
  42. 42.
    Moffett JR, Namboodiri MAA, Cangro CB, Neale JH (1991) Immunohistochemical localization of N-acetylaspartate in rat brain. NeuroReport 2:131–134PubMedCrossRefGoogle Scholar
  43. 43.
    Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45:37–45PubMedCrossRefGoogle Scholar
  44. 44.
    Vrenken H, Barkhof F, Uitdehaag BM et al (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266PubMedCrossRefGoogle Scholar
  45. 45.
    Helms G, Stawiarz L, Kivisakk P, Link H (2000) Regression analysis of metabolite concentrations estimated from localized proton MR spectra of active and chronic multiple sclerosis lesions. Magn Reson Med 43:102–110PubMedCrossRefGoogle Scholar
  46. 46.
    Filippi M, Falini A, Arnold DL et al (2005) Magnetic resonance techniques for the in vivo assessment of multiple sclerosis pathology: consensus report of the White Matter Study Group. J Magn Reson Imaging 21:669–675PubMedCrossRefGoogle Scholar
  47. 47.
    Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13:981–989PubMedGoogle Scholar
  48. 48.
    Davie CA, Barker GJ, Webb S et al (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118:1583–1592PubMedCrossRefGoogle Scholar
  49. 49.
    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
  50. 50.
    Matthews PM, De Stefano N, Narayanan S et al (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol 18:327–336PubMedGoogle Scholar
  51. 51.
    Bitsch A, Bruhn H, Vougioukas V et al (1999) Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am J Neuroradiol 20:1619–1627PubMedGoogle Scholar
  52. 52.
    Sastre-Garriga J, Ingle GT, Chard DT et al (2005) Metabolite changes in normalappearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 62:569–573PubMedCrossRefGoogle Scholar
  53. 53.
    Werner P, Pitt D, Raine CS (2001) Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 50:169–180PubMedCrossRefGoogle Scholar
  54. 54.
    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
  55. 55.
    De Stefano N, Matthews PM, Narayanan S et al (1997) Axonal dysfunction and disability in a relapse of multiple sclerosis: longitudinal study of a patient. Neurology 49:1138–1141PubMedGoogle Scholar
  56. 56.
    Tiberio M, Chard DT, Altmann DR et al (2006) Metabolite changes in early relapsing-remitting multiple sclerosis: a two year follow-up study. J Neurol 253:224–230PubMedCrossRefGoogle Scholar
  57. 57.
    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
  58. 58.
    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 Psychiat 64:204–212PubMedCrossRefGoogle Scholar
  59. 59.
    Narayanan S, De Stefano N, Francis GS et al (2001) Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 248:979–986PubMedCrossRefGoogle Scholar
  60. 60.
    Schubert F, Seifert F, Elster C et al (2002) Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-beta therapy on absolute metabolite concentrations. MAGMA 14:213–222PubMedCrossRefGoogle Scholar
  61. 61.
    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 250:171–178PubMedCrossRefGoogle Scholar
  62. 62.
    Khan O, Shen Y, Caon C et al (2005) Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult Scler 11:646–651PubMedCrossRefGoogle Scholar
  63. 63.
    Narayana PA, Wolinsky JS, Rao SB et al (2004) Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 10(Suppl1):S73–S78PubMedCrossRefGoogle Scholar
  64. 64.
    Leary SM, Brex PA, MacManus DG et al (2000) A 1H magnetic resonance spectroscopy study of aging in parietal white matter: implications for trials in multiple sclerosis. Magn Reson Imaging 18:455–459PubMedCrossRefGoogle Scholar
  65. 65.
    Narayanan S, De Stefano N, Pouwels PJ et al (2005) The effect of oral glatiramer acetate treatment on axonal integrity in multiple sclerosis: results from the multicentre CORAL MRS sub-study. Mult Scler 11(Suppl1):S60Google Scholar
  66. 66.
    Trapp BD, Ransohoff R, Rudick R (1999) Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 12:295–302PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • N. De Stefano
    • 1
  1. 1.Department of Neurological and Behavioral SciencesUniversity of SienaSienaItaly

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