Advertisement

Imaging of Demyelination and Remyelination in Multiple Sclerosis

  • Douglas L. Arnold
  • Catherine M. Dalton
  • Klaus Schmierer
  • G. Bruce Pike
  • David H. Miller
Chapter

Abstract

The ability to estimate myelin content in MS brain is of particular interest given the primary role of demyelination in this disease and the significance of remyelination for axonal preservation and functional recovery. As treatment strategies potentially facilitating remyelination are developed, accurate non-invasive techniques are needed to monitor remyelination in patients with MS. This chapter reviews techniques potentially able to provide this information: multi-component T2 relaxometry, magnetization transfer imaging, diffusion tensor imaging and positron emission tomography, starting with a brief discussion of how they do this, and then reviewing published data on post-mortem MRI correlations and clinical applications.

Keywords

Fractional Anisotropy Diffusion Tensor Imaging Retinal Nerve Fibre Layer Optic Neuritis Visual Evoke Potential 
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.

References

  1. Barkovich AJ (2005) Magnetic resonance techniques in the assessment of myelin and myelination. J Inherit Metab Dis 28:311–343PubMedCrossRefGoogle Scholar
  2. Beaulieu C, Allen PS (1994) Water diffusion in the giant axon of the squid: implications for diffusion-weighted MRI of the nervous system. Magn Reson Med 32:579–583PubMedCrossRefGoogle Scholar
  3. Chen JT, Kuhlmann T, Jansen GH, Collins DL, Atkins HL, Freedman MS, O’Connor PW, Arnold DL (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 36:1152–1158PubMedCrossRefGoogle Scholar
  4. Davies GR, Tozer DJ, Cercignani M, Ramani A, Dalton CM, Thompson AJ, Barker GJ, Tofts PS, Miller DH (2004) Estimation of the macromolecular proton fraction and bound pool T2 in multiple sclerosis. Mult Scler 10:607–613PubMedCrossRefGoogle Scholar
  5. Deloire-Grassin MS, Brochet B, Quesson B, Delalande C, Dousset V, Canioni P, Petry KG (2000) In vivo evaluation of remyelination in rat brain by magnetization transfer imaging. J Neurol Sci 178:10–16PubMedCrossRefGoogle Scholar
  6. Dousset V, Grossman RI, Ramer KN, Schnall MD, Young LH, Gonzalez-Scarano F, et al. (1992) Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology. 182(2):483–91. Epub 1992/02/01.PubMedCrossRefGoogle Scholar
  7. Dousset V, Gayou A, Brochet B, Caille JM (1998) Early structural changes in acute MS lesions assessed by serial magnetization transfer studies. Neurology 51:1150–1155PubMedCrossRefGoogle Scholar
  8. Dula AN, Gochberg DF, Valentine HL, Valentine WM, Does MD (2010) Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord. Magn Reson Med 63:902–909PubMedCrossRefGoogle Scholar
  9. Engelbrecht V, Rassek M, Preiss S, Wald C, Modder U (1998) Age-dependent changes in magnetization transfer contrast of white matter in the pediatric brain. AJNR Am J Neuroradiol 19(10):1923–9. Epub 1999/01/05.PubMedCrossRefGoogle Scholar
  10. Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S (2002) Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis. Mult Scler 8:479–484PubMedCrossRefGoogle Scholar
  11. Filippi M, Rocca MA, Comi G (1998) Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement. J Neurol Sci 159:162–165PubMedCrossRefGoogle Scholar
  12. Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, Volpe NJ, Nano-Schiavi ML, Baier ML, Frohman EM, Winslow H, Frohman TC, Calabresi PA, Maguire MG, Cutter GR, Balcer LJ (2007) Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 113:324–332. doi: 10.1002/ana.21113 PubMedCrossRefGoogle Scholar
  13. Fisher E, Chang A, Fox RJ, Tkach JA, Svarovsky T, Nakamura K, et al. (2006) Imaging correlates of axonal swelling in chronic multiple sclerosis brains. Ann Neurol 62(3):219–28. Epub 2007/04/13.PubMedCrossRefGoogle Scholar
  14. Fralix TA, Ceckler TL, Wolff SD, Simon SA, Balaban RS (1991) Lipid bilayer and water proton magnetization transfer: effect of cholesterol. Magnetic Resonance in Medicine 18(1):214–23.PubMedCrossRefGoogle Scholar
  15. Gass A, Moseley IF, Barker GJ, Jones S, MacManus D, McDonald WI, Miller DH (1996) Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI. Neuroradiology 38:317–321PubMedCrossRefGoogle Scholar
  16. Gloor M, Scheffler K, Bieri O (2008) Quantitative magnetization transfer imaging using balanced SSFP. Magn Reson Med 60:691–700. doi: 10.1002/mrm.21705 PubMedCrossRefGoogle Scholar
  17. Goodkin DE, Rooney WD, Sloan R, Bacchetti P, Gee L, Vermathen M, Waubant E, Abundo M, Majumdar S, Nelson S, Weiner MW (1998) A serial study of new MS lesions and the white matter from which they arise. Neurology 51:1689–1697PubMedCrossRefGoogle Scholar
  18. Gulani V, Webb AG, Duncan ID, Lauterbur PC (2001) Apparent diffusion tensor measurements in myelin-deficient rat spinal cords. Magn Reson Med 45:191–195PubMedCrossRefGoogle Scholar
  19. Henkelman RM, Huang X, Xiang QS, Stanisz GJ, Swanson SD, Bronskill MJ (1993) Quantitative interpretation of magnetization transfer. Magn Reson Res 29:759–766CrossRefGoogle Scholar
  20. Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14:57–64. doi: 10.1002/nbm.683 [pii]PubMedCrossRefGoogle Scholar
  21. Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DG, Barker GJ, Plant GT, Thompson AJ, Miller DH (2004) Serial magnetization transfer imaging in acute optic neuritis. Brain 127:692–700. doi: 10.1093/brain/awh076 PubMedCrossRefGoogle Scholar
  22. Inglese M, Salvi F, Iannucci G, Mancardi GL, Mascalchi M, Filippi M (2002) Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 23:267–272PubMedGoogle Scholar
  23. Kucharczyk W, Macdonald PM, Stanisz GJ, Henkelman RM (1994) Relaxivity and magnetization transfer of white matter lipids at MR imaging: importance of cerebrosides and pH. Radiology 192:521–529PubMedGoogle Scholar
  24. Lai HM, Davie CA, Gass A, Barker GJ, Webb S, Tofts PS, Thompson AJ, McDonald WI, Miller DH (1997) Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis. J Neurol 244:308–311PubMedCrossRefGoogle Scholar
  25. Laule C, Vavasour IM, Moore GR, Oger J, Li DK, Paty DW, MacKay AL (2004) Water content and myelin water fraction in multiple sclerosis. A T2 relaxation study. J Neurol 251:284–293PubMedCrossRefGoogle Scholar
  26. Laule C, Leung E, Lis DK, Traboulsee AL, Paty DW, MacKay AL, Moore GR (2006) Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology. Mult Scler 12:747–753PubMedCrossRefGoogle Scholar
  27. Levesque I, Sled JG, Narayanan S, Santos AC, Brass SD, Francis SJ, Arnold DL, Pike GB (2005) The role of edema and demyelination in chronic T(1) black holes: a quantitative magnetization transfer study. J Magn Reson Imaging 21:103–110PubMedCrossRefGoogle Scholar
  28. Levesque I, Chia CL, Pike GB (2006) The impact of compartmental exchange on estimates of the myelin water fraction. In: ISMRM workshop on imaging myelin: formation, destruction and repair, VancouverGoogle Scholar
  29. Levesque I, Giacomini PS, Narayanan S, Ribeiro L, Sled JG, Arnold DL, Pike GB (2008) Evolution of quantitative magnetization transfer imaging parameters in acute lesions of multiple sclerosis. In: Proceedings of the 16th scientific meeting of the International Society for Magnetic Resonance in Medicine, TorontoGoogle Scholar
  30. MacKay A, Whittall K, Adler J, Li D, Paty D, Graeb D (1994) In vivo visualization of myelin water in brain by magnetic resonance. Magn Reson Med 31:673–677PubMedCrossRefGoogle Scholar
  31. Menon RS, Allen PS (1991) Application of continuous relaxation time distributions to the fitting of data from model systems and excised tissue. Magn Reson Med 20:214–227PubMedCrossRefGoogle Scholar
  32. Menon RS, Rusinko MS, Allen PS (1992) Proton relaxation studies of water compartmentalization in a model neurological system. Magn Reson Med 28:264–274PubMedCrossRefGoogle Scholar
  33. Moore GR, Leung E, MacKay AL, Vavasour IM, Whittall KP, Cover KS, Li DK, Hashimoto SA, Oger J, Sprinkle TJ, Paty DW (2000) A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain. Neurology 55:1506–1510PubMedCrossRefGoogle Scholar
  34. Morrison C, Stanisz G, Henkelman RM (1995) Modeling magnetization transfer for biological-like systems using a semi-solid pool with a super-Lorentzian lineshape and dipolar reservoir. J Magn Reson B 108:103–113PubMedCrossRefGoogle Scholar
  35. Narayanan S, Francis SJ, Sled JG, Santos AC, Antel S, Levesque I, Brass S, Lapierre Y, Sappey-Marinier D, Pike GB, Arnold DL (2006) Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter. Neuroimage 29:637–642PubMedCrossRefGoogle Scholar
  36. Nijeholt GJ, Bergers E, Kamphorst W, Bot J, Nicolay K, Castelijns JA, van Waesberghe JH, Ravid R, Polman CH, Barkhof F (2001) Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. Brain 124:154–166PubMedCrossRefGoogle Scholar
  37. Oouchi H, Yamada K, Sakai K, Kizu O, Kubota T, Ito H, Nishimura T (2007) Diffusion anisotropy measurement of brain white matter is affected by voxel size: underestimation occurs in areas with crossing fibers. AJNR Am J Neuroradiol 28:1102–1106. doi: 10.3174/ajnr.A0488 PubMedCrossRefGoogle Scholar
  38. Pike GB (1996) Pulsed magnetization transfer contrast in gradient echo imaging: a two-pool analytic description of signal response. Magn Reson Med 36:95–103PubMedCrossRefGoogle Scholar
  39. Pike GB, Glover GH, Hu BS, Enzmann DR (1992) Pulsed magnetization transfer spin-echo MR imaging. J Magn Reson 3:531–539Google Scholar
  40. Pike GB, De Stefano N, Narayanan S, Worsley KJ, Pelletier D, Francis GS, Antel JP, Arnold DL (2000) Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images. Radiology 215:824–830PubMedGoogle Scholar
  41. Richert ND, Ostuni JL, Bash CN, Leist TP, McFarland HF, Frank JA (2001) Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult Scler 7:49–58PubMedGoogle Scholar
  42. Rovira A, Alonso J, Cucurella G, Nos C, Tintore M, Pedraza S, Rio J, Montalban X (1999) Evolution of multiple sclerosis lesions on serial contrast-enhanced T1-weighted and magnetization-transfer MR images. AJNR Am J Neuroradiol 20:1939–1945PubMedGoogle Scholar
  43. Schmierer K, Tozer DJ, Scaravilli F, Altmann DR, Barker GJ, Tofts PS, Miller DH (2007) Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain. J Magn Reson Imaging 26:41–51PubMedCrossRefGoogle Scholar
  44. Schmierer K, Wheeler-Kingshott CA, Tozer DJ, Boulby PA, Parkes HG, Yousry TA, Scaravilli F, Barker GJ, Tofts PS, Miller DH (2008) Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation. Magn Reson Med 59:268–277. doi: 10.1002/mrm.21487 PubMedCrossRefGoogle Scholar
  45. Silver NC, Lai M, Symms MR, Barker GJ, McDonald WI, Miller DH (1998) Serial magnetization transfer imaging to characterize the early evolution of new MS lesions. Neurology 51:758–764PubMedCrossRefGoogle Scholar
  46. Silver N, Lai M, Symms M, Barker G, McDonald I, Miller D (1999) Serial gadolinium-enhanced and magnetization transfer imaging to investigate the relationship between the duration of blood-brain barrier disruption and extent of demyelination in new multiple sclerosis lesions. J Neurol 246:728–730. doi: 92460728.415 [pii]PubMedCrossRefGoogle Scholar
  47. Sled JG, Pike GB (2001) Quantitative imaging of magnetization transfer exchange and relaxation properties in vivo using MRI. Magn Reson Med 46:923–931PubMedCrossRefGoogle Scholar
  48. Sled JG, Levesque I, Santos AC, Francis SJ, Narayanan S, Brass SD, Arnold DL, Pike GB (2004) Regional variations in normal brain shown by quantitative magnetization transfer imaging. Magn Reson Med 51:299–303PubMedCrossRefGoogle Scholar
  49. Stanisz GJ, Webb S, Munro CA, Pun T, Midha R (2004) MR properties of excised neural tissue following experimentally induced inflammation. Magn Reson Med 51:473–479PubMedCrossRefGoogle Scholar
  50. Stankoff B, Wang Y, Bottlaender M, Aigrot MS, Dolle F, Wu C, Feinstein D, Huang GF, Semah F, Mathis CA, Klunk W, Gould RM, Lubetzki C, Zalc B (2006) Imaging of CNS myelin by positron-emission tomography. Proc Natl Acad Sci USA 103:9304–9309PubMedCrossRefGoogle Scholar
  51. Stankoff B, Freeman L, Aigrot MS, Chardain A, Dolle F, Williams A, Galanaud D, Armand L, Lehericy S, Lubetzki C, Zalc B, Bottlaender M (2011) Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-(1)(1)C]-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole. Ann Neurol 69:673–680PubMedCrossRefGoogle Scholar
  52. Stewart WA, MacKay AL, Whittall KP, Moore GR, Paty DW (1993) Spin-spin relaxation in experimental allergic encephalomyelitis. Analysis of CPMG data using a non-linear least squares method and linear inverse theory. Magn Reson Med 29:767–775PubMedCrossRefGoogle Scholar
  53. Thorpe JW, Barker GJ, Jones SJ, Moseley I, Losseff N, MacManus DG, Webb S, Mortimer C, Plummer DL, Tofts PS et al (1995) Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology. J Neurol Neurosurg Psychiatry 59:487–492PubMedCrossRefGoogle Scholar
  54. Tofts PS, Cercignani M, Tozer DJ, Symms MR, Davies GR, Ramani A, Barker GJ (2005) Tozer et al. Quantitative magnetization transfer mapping of bound protons in multiple sclerosis, Magn Reson Med 2003;50:83-91. Magn Reson Med 53:492–493CrossRefGoogle Scholar
  55. Trip SA, Schlottmann PG, Jones SJ, Altmann DR, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH (2005) Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 58:383–391. doi: 10.1002/ana.20575 PubMedCrossRefGoogle Scholar
  56. Tyszka JM, Readhead C, Bearer EL, Pautler RG, Jacobs RE (2006) Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant. Neuroimage 29:1058–1065PubMedCrossRefGoogle Scholar
  57. van Buchem MA, Tofts PS (2000) Magnetization transfer imaging. Neuroimaging Clin N Am 10:771–788PubMedGoogle Scholar
  58. Vavasour IM, Whittall KP, MacKay AL, Li DK, Vorobeychik G, Paty DW (1998) A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients. Magn Reson Med 40:763–768PubMedCrossRefGoogle Scholar
  59. Vavasour IM, Li DK, Laule C, Traboulsee AL, Moore GR, Mackay AL (2007) Multi-parametric MR assessment of T(1) black holes in multiple sclerosis: evidence that myelin loss is not greater in hypointense versus isointense T(1) lesions. J Neurol 254:1653–1659. doi: 10.1007/s00415-007-0604-x PubMedCrossRefGoogle Scholar
  60. Vavasour IM, Laule C, Li DK, Oger J, Moore GR, Traboulsee A, MacKay AL (2009) Longitudinal changes in myelin water fraction in two MS patients with active disease. J Neurol Sci 276:49–53PubMedCrossRefGoogle Scholar
  61. Webb S, Munro CA, Midha R, Stanisz GJ (2003) Is multicomponent T2 a good measure of myelin content in peripheral nerve? Magn Reson Med 49:638–645PubMedCrossRefGoogle Scholar
  62. Whittall KP, MacKay AL, Li DK, Vavasour IM, Jones CK, Paty DW (2002) Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T(2). Magn Reson Med 47:403–408. doi: 10.1002/mrm.10076 [pii]PubMedCrossRefGoogle Scholar
  63. Wolff SD, Balaban RS (1989) Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med 10:135–144PubMedCrossRefGoogle Scholar
  64. Yarnykh VL, Yuan C (2004) Cross-relaxation imaging reveals detailed anatomy of white matter fiber tracts in the human brain. Neuroimage 23:409–424PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Douglas L. Arnold
    • 1
  • Catherine M. Dalton
    • 2
  • Klaus Schmierer
    • 3
  • G. Bruce Pike
    • 1
  • David H. Miller
    • 2
  1. 1.McConnell Brain Imaging Centre, WB323, Montreal Neurological InstituteMontrealCanada
  2. 2.Department of Neuroinflammation, The Institute of Neurology (Queen Square)University College LondonLondonUK
  3. 3.Centre for Neuroscience & Trauma, Blizard InstituteBarts and The London School of Medicine & DentistryLondonUK

Personalised recommendations