MR Spectroscopy of the Normal-Appearing Grey Matter

  • O. Gonen
  • M. Inglese
  • R. I. Grossman
Part of the Topics in Neuroscience book series (TOPNEURO)


Multiple sclerosis (MS) has been regarded for over a hundred years as an inflammatory demyelinating disease affecting the white matter (WM) of the central nervous system (CNS) [1]. Only over the past decade has this perception been expanded to accommodate the mounting pathological and MRI evidence of axonal injury in the WM lesions of the brain and cord [2–5]. This damage has been shown to extend well beyond the macroscopic lesions into the so-called normal-appearing WM (NAWM) with varying degrees of severity and extent [6–11].


Multiple Sclerosis Expand Disability Status Scale Multiple Sclerosis Lesion Magnetization Transfer Ratio Expand Disability Status Scale Score 
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  1. 1.
    Charcot J (1868) Histologic de le sclerose en plaques. Gaz Hop (Paris) 141:554–555, 557–558Google Scholar
  2. 2.
    Arnold DL, Matthews PM, Francis G, Antel J (1990) Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med 14:154–159PubMedCrossRefGoogle Scholar
  3. 3.
    Davie CA, Hawkins CP, Barker GJ et al (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 117:49–58PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    van Walderveen MA, Barkhof F, Pouwels PJ et al (1999) Neuronal damage in Tlhypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy. Ann Neurol 46:79–87PubMedCrossRefGoogle Scholar
  6. 6.
    Allen IV, McKeown SR (1979) A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 41:81–91PubMedCrossRefGoogle Scholar
  7. 7.
    Evangelou N, Esiri MM, Smith S et al (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391–395PubMedCrossRefGoogle Scholar
  8. 8.
    Miki Y, Grossman RI, Udupa JK et al (1999) Differences between relapsing-remitting and chronic progressive multiple sclerosis as determined with quantitative MR imaging. Radiology 210:769–774PubMedGoogle Scholar
  9. 9.
    Loevner LA, Grossman RI, Cohen IA et al (1995) Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. Radiology 196:511–515PubMedGoogle Scholar
  10. 10.
    Filippi M, Cercignani M, Inglese M et al (2001) Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology 56:304–311PubMedCrossRefGoogle Scholar
  11. 11.
    Fu L, Matthews PM, De Stefano N et al (1998) Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121:103–113PubMedCrossRefGoogle Scholar
  12. 12.
    Brownell B, Hughes J (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25:315–320PubMedCrossRefGoogle Scholar
  13. 13.
    Lumsden C (1970) The neuropathology of multiple sclerosis. In: Vinken Pj BG (ed) Handbook of clinical neurology. North-Holland, Amsterdam, p 217–309Google Scholar
  14. 14.
    Kidd D, Barkhof F, McConnell R et al (1999) Cortical lesions in multiple sclerosis. Brain 122:17–26PubMedCrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Ge Y, Grossman RI, Udupa JK et al (2001) Magnetization transfer ratio histogram analysis of grey matter in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 22:470–475PubMedGoogle Scholar
  17. 17.
    Kapeller P, McLean MA, Griffin CM et al (2001) Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol 248:131–138PubMedCrossRefGoogle Scholar
  18. 18.
    Sharma R, Narayana PA, Wolinsky JS (2001) Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging. Mult Scler 7:221–226PubMedGoogle Scholar
  19. 19.
    Bozzali M, Cercignani M, Sormani MP et al (2002) Quantification of brain grey matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR Am J Neuroradiol 23:985–988PubMedGoogle Scholar
  20. 20.
    Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45:37–45PubMedCrossRefGoogle Scholar
  21. 21.
    Matthews PM, Pioro E, Narayanan S et al (1996) Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. Brain 119:715–722PubMedCrossRefGoogle Scholar
  22. 22.
    Gonen O, Catalaa I, Babb JS et al (2000) Total brain N-acetylaspartate: a new measure of disease load in MS. Neurology 54:15–19PubMedCrossRefGoogle Scholar
  23. 23.
    De Stefano N, Narayanan S, Mortilla M et al (2000) Imaging axonal damage in multiple sclerosis by means of MR spectroscopy. Neurol Sci 21:S883–887PubMedCrossRefGoogle Scholar
  24. 24.
    Li BS, Babb JS, Soher BJ et al (2002) Reproducibility of 3D proton spectroscopy in the human brain. Magn Reson Med 47:439–446PubMedCrossRefGoogle Scholar
  25. 25.
    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
  26. 26.
    Miki Y, Grossman RI, Udupa JK et al (1999) Relapsing-remitting multiple sclerosis: longitudinal analysis of MR images-lack of correlation between changes in T2 lesion volume and clinical findings. Radiology 213:395–399PubMedGoogle Scholar
  27. 27.
    Courchesne E, Chisum HJ, Townsend J et al (2000) Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology 216:672–682PubMedGoogle Scholar
  28. 28.
    Wang Y, Li SJ (1998) Differentiation of metabolic concentrations between grey matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 39:28–33PubMedCrossRefGoogle Scholar
  29. 29.
    Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911PubMedCrossRefGoogle Scholar
  30. 30.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedCrossRefGoogle Scholar
  31. 31.
    Udupa JK, Odhner D, Samarasekera S (1994) 3DVIEWNIX: an open, transportable, multdimensional, multimodality, multiparametric imging software system. Proc SPIE 2164:58–73CrossRefGoogle Scholar
  32. 32.
    Udupa JK, Samarasekera S (1996) Fuzzy connectedness and object definition: theory, algorithms, and applications in image segmentation. Graph Models Image Process 58:246–261CrossRefGoogle Scholar
  33. 33.
    Ge Y, Grossman RI, Udupa JK et al (2000) Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis. Radiology 214:665–670PubMedGoogle Scholar
  34. 34.
    Udupa JK, Wei L, Miki Y, Grossman RI (1997) A system for the comprehensive analysis of multiple sclerosis lesion load based on MR imagery [abstract]. In: Proceedings of the Society of Photo-Optical Instrumentation Engineers program. Newport Beach, Calif, pp 610–618Google Scholar
  35. 35.
    Samarasekera S, Udupa JK, Miki Y et al (1997) A new computer-assisted method for the quantification of enhancing lesions in multiple sclerosis. J Comput Assist Tomogr 21:145–151PubMedCrossRefGoogle Scholar
  36. 36.
    Soher BJ, van Zijl PC, Duyn JH, Barker PB (1996) Quantitative proton MR spectroscopic imaging of the human brain. Magn Reson Med 35:356–363PubMedCrossRefGoogle Scholar
  37. 37.
    Hoult DI, Richards RE (1976) The signal-to-noise ratio of the nuclear magnetic resonance experiment. J Magn Reson 24:71–85Google Scholar
  38. 38.
    Arnold DL, De Stefano N, Narayanan S, Matthews PM (2000) Proton MR spectroscopy in multiple sclerosis. Neuroimaging Clin North Am 10:789–798, ix-xGoogle Scholar
  39. 39.
    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
  40. 40.
    Bjartmar C, Kidd G, Mork S et al (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901PubMedCrossRefGoogle Scholar
  41. 41.
    Bjartmar C, Kinkel RP, Kidd G et al (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248–1252PubMedCrossRefGoogle Scholar
  42. 42.
    Cifelli A, Arridge M, Jezzard P et al (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653PubMedCrossRefGoogle Scholar
  43. 43.
    Filippi M, Bozzali M, Rovaris M et al (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126:433–437PubMedCrossRefGoogle Scholar
  44. 44.
    Martin WRW, Snow B, Ashforth R (1999) Abnormalities of movement and posture due to disease of the extrapyramidal motor system. In: Greenberg JO (eds) Neuro-imaging-a companion to Adams and Victor’s principles of neurology. McGraw-Hill, New YorkGoogle Scholar
  45. 45.
    Filippi M, Bozzali M, Comi G (2001) Magnetization transfer and diffusion tensor MR imaging of basal ganglia from patients with multiple sclerosis. J Neurol Sci 183:69–72PubMedCrossRefGoogle Scholar
  46. 46.
    Gonen O, Grossman RI (2001) New magnetic resonance spectroscopy strategies. In: Comi G (ed) Magnetic resonance spectroscopy in multiple sclerosis. Springer, Milan, pp 97–112CrossRefGoogle Scholar
  47. 47.
    Wylezinska M, Cifelli A, Jezzard P et al (2003) Thalamic neurodegeneration in relapsingremitting multiple sclerosis. Neurology 60:1949–1954PubMedCrossRefGoogle Scholar
  48. 48.
    Soher BJ, Young K, Govindaraju V, Maudsley AA (1998) Automated spectral analysis III: Application to in vivo proton MR spectroscopy and spectroscopic imaging. Magn Reson Med 40:822–831PubMedCrossRefGoogle Scholar
  49. 49.
    Inglese M, Li BS, Rusinek H et al (2003) Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med 50:190–195PubMedCrossRefGoogle Scholar
  50. 50.
    Kreis R, Ernst T, Ross BD (1993) Absolute concentrations of water and metabolites in the human brain. II. Metabolite concentrations. J Magn Reson 102:9–19CrossRefGoogle Scholar
  51. 51.
    Christiansen P, Toft P, Larsson HB et al (1993) The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium. Magn Reson Imaging 11:799–806PubMedCrossRefGoogle Scholar
  52. 52.
    Ernst RR, Bodenhausen G, Wokaun A (1987) Principles of nuclear magnetic resonance in one and two dimensions. Clarendon Press, Oxford, p 152Google Scholar
  53. 53.
    Helms G (2001) Volume correction for edema in single-volume proton MR spectroscopy of contrast-enhancing multiple sclerosis lesions. Magn Reson Med 46:256–263PubMedCrossRefGoogle Scholar
  54. 54.
    Calabresi P, Centonze D, Bernardi G (2000) Cellular factors controlling neuronal vulnerability in the brain: a lesson from the striatum. Neurology 55:1249–1255PubMedCrossRefGoogle Scholar
  55. 55.
    Roelcke U, Kappos L, Lechner-Scott J et al (1997) Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48:1566–1571PubMedCrossRefGoogle Scholar
  56. 56.
    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
  57. 57.
    Blinkenberg M, Rune K, Jensen CV et al (2000) Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS. Neurology 54:558–564PubMedCrossRefGoogle Scholar
  58. 58.
    Chard DT, Griffin CM, Parker GJ et al (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337PubMedCrossRefGoogle Scholar
  59. 59.
    De Stefano N, Matthews PM, Filippi M et al (2003) Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 60:1157–1162PubMedCrossRefGoogle Scholar
  60. 60.
    Rao SM, Leo GJ, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41:685–691Google Scholar

Copyright information

© Springer-Verlag Italia 2004

Authors and Affiliations

  • O. Gonen
  • M. Inglese
  • R. I. Grossman

There are no affiliations available

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