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Magnetic resonance imaging techniques to define and monitor tissue damage and repair in multiple sclerosis

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Abstract

Conventional magnetic resonance imaging (cMRI) has greatly improved our ability to diagnose multiple sclerosis (MS) and to monitor its evolution, either natural or modified by treatment. cMRI-derived measures have indeed shown several advantages over clinical assessment, including their more objective nature and increased sensitivity to MS-related changes. Nevertheless, the magnitude of the relationship between cMRI measures of disease activity or burden and the clinical manifestations of the disease is weak. Several factors are likely to be responsible for this clinical/MRI discrepancy, including the poor specificity of dual-echo scans with regard to the heterogeneous pathological substrates of individual lesions and the inability of T2-weighted images to delineate tissue damage occurring in the normal-appearing white matter (NAWM) and grey matter (GM).

Recently, several non-conventional MRI techniques have been developed and applied in an attempt to improve our understanding of the evolution of MS. These techniques, including magnetization transfer (MT) MRI, diffusion tensor (DT) MRI, and proton MR spectroscopy (1H-MRS) may provide quantitative information about MS micro- and macroscopic lesion burdens with a higher pathological specificity to the most destructive aspects of the disease (i.e., severe demyelination and axonal loss) than cMRI. In addition, their application in longitudinal studies is progressively improving our ability to monitor reparative mechanisms, such as resolution of edema, remyelination, reactive gliosis and recovery from sublethal axonal injury. Finally, functional MRI (fMRI) holds substantial promise to define the role of adaptive cortical reorganization with the potential to limit the clinical consequences of irreversible MS tissue injury.

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References

  1. Agosta F, Benedetti B, Rocca MA, Valsasina P, Rovaris M, Comi G, Filippi M (2005) Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI. Neurology 64:631-35

    CAS  PubMed  Google Scholar 

  2. Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M (2006) Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain 129:2620-627

    Article  PubMed  Google Scholar 

  3. Allen IV, McKeown SR (1979) A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 41:81-1

    Article  CAS  PubMed  Google Scholar 

  4. Arnold DL (1999) Magnetic resonance spectroscopy: imaging axonal damage in MS. J Neuroimmunol 98:2-

    Article  CAS  PubMed  Google Scholar 

  5. Barkhof F (2002) The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 15:239-45

    Article  PubMed  Google Scholar 

  6. Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitativediffusion-tensor MRI. J Magn Reson B 111:209-19

    Article  CAS  PubMed  Google Scholar 

  7. Benedetti B, Valsasina P, Judica E, Martinelli V, Ghezzi A, Capra R, Bergamaschi R, Comi G, Filippi M (2006) Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI. Neurology 67:161-63

    Article  CAS  PubMed  Google Scholar 

  8. Bitsch A, Bruhn H, Vougioukas V, Stringaris A, Lassmann H, Frahm J, Bruck W (1999) Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative MR spectroscopy. Am J Neuroradiol 20:1619-627

    CAS  PubMed  Google Scholar 

  9. Bozzali M, Cercignani M, Sormani MP, Comi G, Filippi M (2002) Quantification of brain gray matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR Am J Neuroradiol 23:985-88

    PubMed  Google Scholar 

  10. Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH (2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158-64

    Article  PubMed  Google Scholar 

  11. Cader S, Cifelli A, Abu-Omar Y, Palace J, Matthews PM (2006) Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. Brain 129:527-37

    Article  PubMed  Google Scholar 

  12. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M (2001) Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 70:311-17

    Article  CAS  PubMed  Google Scholar 

  13. Sormani MP, Ferrante P, Filippi M (2006) Cervical cord MTR and clinical changes over 18 months in patients with relapsing-remitting MS: a preliminary study. Mult Scler 12:662-65

    Article  PubMed  Google Scholar 

  14. Ciccarelli O, Toosy AT, Hickman SJ, Parker GJ, Wheeler-Kingshott CA, Miller DH, Thompson AJ (2005) Optic radiation changes after optic neuritis detected by tractography-based group mapping. Hum Brain Mapp 25:308-16

    Article  PubMed  Google Scholar 

  15. Clark CA, Werring DJ, Miller DH (2000) Diffusion imaging of the spinal cord in vivo: estimation of the principal diffusivities and application to multiple sclerosis. Magn Reson Med 43:133-38

    Article  CAS  PubMed  Google Scholar 

  16. Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391-95

    Article  CAS  PubMed  Google Scholar 

  17. Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM (2001) Sizeselective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 124:1813-820

    Article  CAS  PubMed  Google Scholar 

  18. Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393-99

    Article  PubMed  Google Scholar 

  19. Filippi M, Horsfield MA, Ader HJ et al. (1998) Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis. Ann Neurol 43:499-06

    Article  CAS  PubMed  Google Scholar 

  20. Filippi M, Tortorella C, Rovaris M, Bozzali M, Possa F, Sormani MP, Iannucci G, Comi G (2000) Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry 68:157-61

    Article  CAS  PubMed  Google Scholar 

  21. Filippi M, Bozzali M, Horsfield MA, Rocca MA, Sormani MP, Iannucci G, Colombo B, Comi G (2000) A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology 54:207-13

    CAS  PubMed  Google Scholar 

  22. Filippi M, Grossman RI (2002) MRI techniques to monitor MS evolution: the present and the future. Neurology 58:1147-153

    PubMed  Google Scholar 

  23. Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G (2002) Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. NeuroImage 15:559-67

    Article  CAS  PubMed  Google Scholar 

  24. Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G (2002) Correlations between structural CNS damage and functional MRI changes in primary progressive MS. NeuroImage 15:537-46

    Article  CAS  PubMed  Google Scholar 

  25. Filippi M, Rocca MA, Comi G (2003) The use of quantitative magnetic-resonance-based techniques to monitor the evolution of multiple sclerosis. Lancet Neurol 2:337-46

    Article  CAS  PubMed  Google Scholar 

  26. Filippi M, Rocca MA (2004) Cortical reorganisation in patients with MS. J Neurol Neurosurg Psychiatry 75:1087-089

    Article  CAS  PubMed  Google Scholar 

  27. Filippi M, Rocca MA, Mezzapesa DM, Ghezzi A, Falini A, Martinelli V, Scotti G, Comi G (2004) Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Hum Brain Mapp 21:108-17

    Article  PubMed  Google Scholar 

  28. Filippi M, Rocca MA, Mezzapesa DM, Falini A, Colombo B, Scotti G, Comi G (2004) A functional MRI study of cortical activations associated with object manipulation in patients with MS. NeuroImage 21:1147-154

    Article  PubMed  Google Scholar 

  29. Ge Y, Grossman RI, Udupa JK, Babb JS, Mannon LJ, McGowan JC (2002) Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis. J Comput Assist Tomogr 26:62-8

    Article  PubMed  Google Scholar 

  30. Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236:254-60

    Article  PubMed  Google Scholar 

  31. Hickman SJ, Toosy AT, Jones SJ et al. (2004) Serial magnetization transfer imaging in acute optic neuritis. Brain 127:692-00

    Article  CAS  PubMed  Google Scholar 

  32. Hickman SJ, Wheeler-Kingshott CA, Jones SJ, Miszkiel KA, Barker GJ, Plant GT, Miller DH (2005) Optic nerve diffusion measurement from diffusion-weighted imaging in optic neuritis. AJNR Am J Neuroradiol 26:951-56

    PubMed  Google Scholar 

  33. Inglese M, Ghezzi A, Bianchi S, Gerevini S, Sormani MP, Martinelli V, Comi G, Filippi M (2002) Irreversible disability and tissue loss in multiple sclerosis: a conventional and magnetization transfer magnetic resonance imaging study of the optic nerves. Arch Neurol 59:250-55

    Article  PubMed  Google Scholar 

  34. Inglese M, Ge Y, Filippi M, Falini A, Grossman RI, Gonen O (2004) Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis. NeuroImage 21:1825-829

    Article  PubMed  Google Scholar 

  35. Iwasawa T, Matoba H, Ogi A, Kurihara H, Saito K, Yoshida T, Matsubara S, Nozaki A (1997) Diffusion-weighted imaging of the human optic nerve: a new approach to evaluate optic neuritis in multiple sclerosis. Magn Reson Med 38:484-91

    Article  CAS  PubMed  Google Scholar 

  36. Kangarlu A, Rammohan KW, Bourekas EC, RayChaudhry A (2004) Imaging of cortical lesions in multiple sclerosis. Proceedings of the 12th Meeting of the International Society of Magnetic Resonance in Medicine. Kyoto, Japan

  37. Kappos L, Moeri D, Radue EW et al. (1999) 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 353:964-69

    Article  CAS  PubMed  Google Scholar 

  38. Kidd D, Barkhof F, McConnel R, Algra PR, Allen IV, Revesz T (1999) Cortical lesions in multiple sclerosis. Brain 122:17-6

    Article  PubMed  Google Scholar 

  39. Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeanter M (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161:401-07

    CAS  PubMed  Google Scholar 

  40. Le Bihan D, Turner R, Pekar J, Moonen CTW (1991) Diffusion and perfusion imaging by gradient sensitization: design, strategy and significance. J Magn Reson Imaging 1:7-

    Article  CAS  PubMed  Google Scholar 

  41. Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, Chabriat H (2001) Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 13:534-46

    Article  CAS  PubMed  Google Scholar 

  42. Melzi L, Rocca A, Bianchi Marzoli S, Falini A, Vezzulli P, Ghezzi A, Brancato R, Comi G, Scotti G, Filippi M (2007) A longitudinal conventional and magnetization transfer MRI study of optic neuritis. Mult Scler, (in press)

  43. Miller DH, Albert PS, Barkhof F et al. (1996) Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. US National MS Society Task Force. Ann Neurol 39:6?16

    Article  CAS  PubMed  Google Scholar 

  44. Miller DH, Barkhof F, Frank JA, Parker GJ, Thompson AJ (2002) Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 125:1676-695

    Article  PubMed  Google Scholar 

  45. Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64:803-12

    Article  CAS  PubMed  Google Scholar 

  46. Ogawa S, Menon RS, Kim SG, Ugurbil K (1998) On the characteristics of functional magnetic resonance imaging of the brain. Annu Rev Biophys Biomol Struct 27:447-74

    Article  CAS  PubMed  Google Scholar 

  47. Oreja-Guevara C, Rovaris M, Iannucci G et al. (2005) Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study. Arch Neurol 62:578-84

    Article  PubMed  Google Scholar 

  48. Oreja-Guevara C, Charil A, Caputo D, Cavarretta R, Sormani MP, Filippi M (2006) MT MRI reflects clinical changes over 18 months in relapsing-remitting MS patients. Arch Neurol 63:736-40

    Article  PubMed  Google Scholar 

  49. Pagani E, Filippi M, Rocca MA, Horsfield MA (2005) A method for obtaining tract-specific diffusion tensor MRI measurements in the presence of disease: application to patients with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 26:258-65

    Article  CAS  PubMed  Google Scholar 

  50. Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389-00

    Article  CAS  PubMed  Google Scholar 

  51. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G (1996) Diffusion tensor MR imaging of the human brain. Radiology 201:637-48

    CAS  PubMed  Google Scholar 

  52. Polman CH, Reingold SC, Edan G et al. (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria- Ann Neurol 58:840-46

    Article  PubMed  Google Scholar 

  53. Reddy H, Narayanan S, Matthews PM, Hoge RD, Pike GB, Duquette P, Antel J, Arnold DL (2000) Relating axonal injury to functional recovery in MS. Neurology 54:236-39

    CAS  PubMed  Google Scholar 

  54. Rocca MA, Mastronardo G, Rodegher M, Comi G, Filippi M (1999) Longterm changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. AJNR Am J Neuroradiol 20:821-27

    CAS  PubMed  Google Scholar 

  55. Rocca MA, Falini A, Colombo B, Scotti G, Comi G, Filippi M (2002) Adaptive functional changes in the cerebral cortex of patients with non-disabling MS correlate with the extent of brain structural damage. Ann Neurol 51:330-39

    Article  PubMed  Google Scholar 

  56. Rocca MA, Matthews PM, Caputo D, Ghezzi A, Falini A, Scotti G, Comi G, Filippi M (2002) Evidence for widespread movement-associated functional MRI changes in patients with PPMS. Neurology 58:866-72

    CAS  PubMed  Google Scholar 

  57. Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2003) Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 18:847-55

    Article  PubMed  Google Scholar 

  58. Rocca MA, Gavazzi C, Mezzapesa DM, Falini A, Colombo B, Mascalchi M, Scotti G, Comi G, Filippi M (2003) A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis. Neuroimage 19:1770-777

    Article  PubMed  Google Scholar 

  59. Rocca MA, Colombo B, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2005) Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes. Lancet Neurol 4:618-26

    Article  PubMed  Google Scholar 

  60. Rocca MA, Agosta F, Colombo B, Mezzapesa DM, Falini A, Comi G, Filippi M (2006) fMRI changes in relapsingremitting multiple sclerosis patients complaining of fatigue after IFNbeta-1a injection. Hum Brain Mapp 24; (Epub ahead of print)

  61. Rovaris M, Filippi M (1999) Magnetic resonance techniques to monitor disease evolution and treatment trial outcomes in multiple sclerosis. Curr Opin Neurol 12:337-44

    Article  CAS  PubMed  Google Scholar 

  62. Rovaris M, Filippi M (2001) Correlations between magnetic resonance spectroscopy and other magnetic resonance parameters in multiple sclerosis. In: Filippi M, Arnold DL, Comi G (eds) Magnetic resonance spectroscopy in multiple sclerosis. Springer, Milan, pp 79-6

  63. Rovaris M, Bozzali M, Santuccio G et al. (2001) In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 124:2540-549

    Article  CAS  PubMed  Google Scholar 

  64. Rovaris M, Agosta F, Sormani MP, Inglese M, Martinelli V, Comi G, Filippi M (2003) Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study. Brain 126:2323-332

    Article  PubMed  Google Scholar 

  65. Rovaris M, Gallo A, Riva R et al. (2004) An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS. Neurology 63:584-85

    CAS  PubMed  Google Scholar 

  66. Rovaris M, Judica E, Gallo A et al. (2006) Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years. Brain 129:2628-634

    Article  CAS  PubMed  Google Scholar 

  67. Sastre-Garriga J, Ingle GT, Chard DT, Cercignani M, Ramio-Torrenta L, Miller DH, Thompson AJ (2005) Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain 128:1454-460

    Article  PubMed  Google Scholar 

  68. Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH (2004) Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol 56:407-15

    Article  PubMed  Google Scholar 

  69. Thorpe JW, Barker GJ, Jones SJ et al. (1995) Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology. J Neurol Neurosurg Psychiatry 58:487-92

    Article  Google Scholar 

  70. Tortorella C, Viti B, Bozzali M, Sormani MP, Rizzo G, Gilardi MF, Comi G, Filippi M (2000) A magnetization transfer histogram study of normal appearing brain tissue in multiple sclerosis. Neurology 54:186-93

    CAS  PubMed  Google Scholar 

  71. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278-85

    Article  CAS  PubMed  Google Scholar 

  72. Trip SA, Wheeler-Kingshott C, Jones SJ, Li WY, Barker GJ, Thompson AJ, Plant GT, Miller DH (2006) Optic nerve diffusion tensor imaging in optic neuritis. Neuroimage 30:498-05

    Article  PubMed  Google Scholar 

  73. Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M (2005) Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology 65:1126-128

    Article  CAS  PubMed  Google Scholar 

  74. Valsasina P, Rocca MA, Agosta F, Benedetti B, Horsfield MA, Gallo A, Rovaris M, Comi G, Filippi M (2005) Mean diffusivity and fractional anisotropy histogram analysis of the cervical cord in MS patients. Neuro-Image 26:822-28

    PubMed  Google Scholar 

  75. van Buchem MA, McGowan JC, Kolson DL, Polansky M, Grossman RI (1996) Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden. Magn Reson Med 36:632-36

    Article  CAS  PubMed  Google Scholar 

  76. van Waesberghe JH, van Walderveen MA, Castelijns JA, Scheltens P, Lycklama a Nijeholt GJ, Polman CH, Barkhof F (1998) Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization MR. AJNR Am J Neuroradiol 19:675-83

    CAS  PubMed  Google Scholar 

  77. van Waesberghe JH, Kamphorst W, De Groot CJ et al. (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46:747-54

    Article  CAS  PubMed  Google Scholar 

  78. Wolff SD, Balaban RS (1994) Magnetization transfer imaging: practical aspects and cinical applications. Radiology 192:593-99

    CAS  PubMed  Google Scholar 

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Filippi, M., Rocca, M.A. Magnetic resonance imaging techniques to define and monitor tissue damage and repair in multiple sclerosis. J Neurol 254 (Suppl 1), I55–I62 (2007). https://doi.org/10.1007/s00415-007-1010-0

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