Skip to main content Accessibility help
  • Print publication year: 2011
  • Online publication date: December 2011

10 - Measures of magnetization transfer

from Section II - Clinical trial methodology


This chapter focuses on how the immune system is thought to contribute to the multiple sclerosis (MS) process through the different disease phases, including initiation and propagation, and in different anatomical compartments. Several subsets of regulatory T-cells are capable of inhibiting activation of other T-cells, including suppression of autoimmune responses. Clinical trials of B-cell depletion with rituximab and more recently ocrelizumab have demonstrated substantial reductions in new brain lesions, and relapses in MS patients. The innate immune system rapidly senses foreign pathogen-associated structures without the need for adaptive antigen-specific recognition or memory responses. The presence of clonally expanded CD4 and CD8 T-cells persisting in the CNS, suggests that T-cells can be activated or re-activated within the central nervous system (CNS) compartment. Cellular immune responses and soluble factors can have protective and potentially growth permissive influences capable of limiting injury, as well as promoting survival and repair of neural elements.


1. Filippi M, Agosta F. Imaging biomarkers in multiple sclerosis. J Magn Reson Imaging 2010; 31:770–88.
2. Katz D, Taubenberger JK, Cannella B, McFarlin DE, Raine CS, McFarland HF. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann Neurol 1993; 34:661–9.
3.van Walderveen MA, Kamphorst W, Scheltens P, et al. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 1998; 50:1282–8.
4. Bloch F. Nuclear induction. Phys Rev 1946; 70:460–74.
5. Forsen S, Hoffman R. Exchange rates by nuclear magnetic multiple resonance. III. Exchange reactions in systems with several nonequivalent sites. J Chem Phys 1964; 40:1189–96.
6. Wolff SD, Balaban RS. Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med 1989; 10:135–44.
7. McGowan JC, Leigh JS, Jr. Selective saturation in magnetization transfer experiments Magn Reson Med 1994; 32:517–22.
8. McGowan JC, 3rd, Schnall MD, Leigh JS. Magnetization transfer imaging with pulsed off-resonance saturation: variation in contrast with saturation duty cycle. J Magn Reson Imaging 1994; 4:79–82.
9. Dousset V, Grossman RI, Ramer KN, et al. Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology 1992; 182:483–91.
10.van Waesberghe JH, Kamphorst W, De Groot CJ, et al. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 1999; 46:747–54.
11. Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol 2004; 56:407–15.
12. Dousset V, Armand JP, Lacoste D, et al. Magnetization transfer study of HIV encephalitis and progressive multifocal leukoencephalopathy. Groupe d’Epidemiologie Clinique du SIDA en Aquitaine. Am J Neuroradiol 1997; 18:895–901.
13. Kasner SE, Galetta SL, McGowan JC, Grossman RI. Magnetization transfer imaging in progressive multifocal leukoencephalopathy. Neurology 1997; 48:534–36.
14. Silver NC, Barker GJ, MacManus DG, Miller DH, Thorpe JW, Howard RS. Decreased magnetisation transfer ratio due to demyelination: a case of central pontine myelinolysis, J Neurol Neurosurg Psychiatry 1996; 61:208–9.
15. Thorpe JW, Barker GJ, Jones SJ, et al. Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology. J Neurol Neurosurg Psychiatry 1995; 59:487–92.
16. McDonald WI, Miller DH, Barnes D. The pathological evolution of multiple sclerosis, Neuropathol Appl Neurobiol 1992; 18:319–34.
17. Hickman SJ, Toosy AT, Jones SJ, et al. Serial magnetization transfer imaging in acute optic neuritis. Brain 2004; 127:692–700.
18. Moore GR, Leung E, MacKay AL, et al. A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain. Neurology 2000; 55:1506–10.
19. Tozer DJ, Davies GR, Altmann DR, Miller DH, Tofts PS. Correlation of apparent myelin measures obtained in multiple sclerosis patients and controls from magnetization transfer and multicompartmental T2 analysis. Magn Reson Med 2005; 53:1415–22.
20. Kimura H, Grossman RI, Lenkinski RE, Gonzalez-Scarano F. Proton MR spectroscopy and magnetization transfer ratio in multiple sclerosis: correlative findings of active versus irreversible plaque disease. AJNR Am J Neuroradiol 1996; 17:1539–47.
21. Loevner LA, Grossman RI, McGowan JC, Ramer KN, Cohen JA. Characterization of multiple sclerosis plaques with T1-weighted MR and quantitative magnetization transfer. Am J Neuroradiol 1995; 16:1473–9.
22. Cercignani M, Iannucci G, Rocca MA, Comi G, Horsfield MA, Filippi M. Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI. Neurology 2000; 54:1139–44.
23. Filippi M, Tortorella C, Bozzali M. Normal-appearing white matter changes in multiple sclerosis: the contribution of magnetic resonance techniques. Mult Scler 1999; 5:273–82.
24. McGowan JC, McCormack TM, Grossman RI, et al. Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig. Magn Reson Med 1999; 41:727–33.
25.van Buchem MA, McGowan JC, Kolson DL, Polansky M, Grossman RI. Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden. Magn Reson Med 1996; 36:632–6.
26. Sormani MP, Iannucci G, Rocca MA, et al. Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers. Am J Neuroradiol 2000; 21:133–6.
27. Inglese M, Horsfield MA, Filippi M. Scan-rescan variation of measures derived from brain magnetization transfer ratio histograms obtained in healthy volunteers by use of a semi-interleaved magnetization transfer sequence Am J Neuroradiol 2001; 22:681–4.
28. Audoin B, Ranjeva JP, Au Duong MV, et al. Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis. J Magn Reson Imaging 2004; 20:765–71.
29. Ranjeva JP, Audoin B, Au Duong MV, et al. Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. AJNR Am J Neuroradiol 2005; 26:119–27.
30. Gawne-Cain ML, O’Riordan JI, Coles A, Newell B, Thompson AJ, Miller DH. MRI lesion volume measurement in multiple sclerosis and its correlation with disability: a comparison of fast fluid attenuated inversion recovery (fFLAIR) and spin echo sequences. J Neurol Neurosurg Psychiatry 1998; 64:197–203.
31. Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346:158–64.
32. Kermode AG, Tofts PS, Thompson AJ, et al. Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement. Neurology 1990; 40:229–35.
33. Filippi M, Rovaris M, Capra R, et al. A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials. Brain 1998; 121:2011–20.
34. Bastianello S, Gasperini C, Paolillo A, et al. Sensitivity of enhanced MR in multiple sclerosis: effects of contrast dose and magnetization transfer contrast. Am J Neuroradiol 1998; 19:1863–7.
35. Silver NC, Good CD, Sormani MP, et al. A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis J Neurol 2001; 248:215–24.
36. Silver NC, Lai M, Symms MR, Barker GJ, McDonald WI, Miller DH. Serial magnetization transfer imaging to characterize the early evolution of new MS lesions. Neurology 1998; 51:758–64.
37. Petrella JR, Grossman RI, McGowan JC, Campbell G, Cohen JA. Multiple sclerosis lesions: relationship between MR enhancement pattern and magnetization transfer effect. Am J Neuroradiol 1996; 17:1041–9.
38. van Waesberghe JH, van Walderveen MA, Castelijns JA, et al. Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. Am J Neuroradiol 1998; 19:675–83.
39. Filippi M, Rocca MA, Comi G. Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement. J Neurol Sci 1998; 159:162–5.
40. Filippi M, Rocca MA, Rizzo G, et al. Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium. Neurology 1998; 50:1289–93.
41. Filippi M, Rocca MA, Martino G, Horsfield MA, Comi G. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann Neurol 1998; 43:809–14.
42. Goodkin DE, Rooney WD, Sloan R, et al. A serial study of new MS lesions and the white matter from which they arise. Neurology 1998; 51:1689–97.
43. Lai HM, Davie CA, Gass A, et al. Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis. J Neurol 1997; 244:308–11.
44. Dousset V, Gayou A, Brochet B, Caille JM. Early structural changes in acute MS lesions assessed by serial magnetization transfer studies. Neurology 1998; 51:1150–5.
45. Rocca MA, Mastronardo G, Rodegher M, Comi G, Filippi M. Long-term changes of magnetization transfer-derived measures from patients with relapsing–remitting and secondary progressive multiple sclerosis. Am J Neuroradiol 1999; 20:821–7.
46. Filippi M, Rocca MA, Sormani MP, Pereira C, Comi G. Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging. Magn Reson Imaging 1999; 17:979–84.
47. Chen JT, Collins DL, Atkins HL, Freedman MS, Arnold DL. Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions. Ann Neurol 2008; 63:254–62.
48. Lassmann H, Suchanek G, Ozawa K. Histopathology and the blood-cerebrospinal fluid barrier in multiple sclerosis. Ann Neurol 1994; 36 Suppl:S42–6.
49. Horsfield MA, Rocca MA, Cercignani M, Filippi M. Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report. Magn Reson Imaging 2000; 18:139–42.
50. Kappos L, Moeri D, Radue EW, et al. 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 1999; 353:964–9.
51. Filippi M, Campi A, Dousset V, et al. A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis, Neurology 1995; 45:478–82.
52. Loevner LA, Grossman RI, Cohen JA, Lexa FJ, Kessler D, Kolson DL. Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. Radiology 1995; 196:511–515.
53. Gass A, Barker GJ, Kidd D, et al. Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis. Ann Neurol 1994; 36:62–7.
54. Guo AC, Jewells VL, Provenzale JM. Analysis of normal-appearing white matter in multiple sclerosis: comparison of diffusion tensor MR imaging and magnetization transfer imaging. Am J Neuroradiol 2001; 22:1893–900.
55. Wong KT, Grossman RI, Boorstein JM, Lexa FJ, McGowan JC. Magnetization transfer imaging of periventricular hyperintense white matter in the elderly. Am J Neuroradiol 1995; 16:253–8.
56. Rovaris M, Viti B, Ciboddo G, et al. Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 2000; 68:170–7.
57. Gupta RK, Kathuria MK, Pradhan S. Magnetization transfer MR imaging in CNS tuberculosis. Am J Neuroradiol 1999; 20:867–75.
58. Bagley LJ, Grossman RI, Galetta SL, Sinson GP, Kotapka M, McGowan JC. Characterization of white matter lesions in multiple sclerosis and traumatic brain injury as revealed by magnetization transfer contour plots. Am J Neuroradiol 1999; 20:977–81.
59. Rocca MA, Colombo B, Pratesi A, Comi G, Filippi M. A magnetization transfer imaging study of the brain in patients with migraine. Neurology 2000; 54:507–9.
60. Tanabe JL, Ezekiel F, Jagust WJ, et al. Magnetization transfer ratio of white matter hyperintensities in subcortical ischemic vascular dementia. Am J Neuroradiol 1999; 20:839–44.
61. Kato Y, Matsumura K, Kinosada Y, Narita Y, Kuzuhara S, Nakagawa T. Detection of pyramidal tract lesions in amyotrophic lateral sclerosis with magnetization-transfer measurements. Am J Neuroradiol 1997; 18:1541–7.
62. Iannucci G, Dichgans M, Rovaris M, et al. Correlations between clinical findings and magnetization transfer imaging metrics of tissue damage in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Stroke 2001; 32:643–8.
63. Inglese M, Rovaris M, Bianchi S, et al. 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 2001; 70:444–9.
64. Inglese M, Salvi F, Iannucci G, Mancardi GL, Mascalchi M, Filippi M. Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 2002; 23:267–272.
65. Enzinger C, Strasser-Fuchs S, Ropele S, Kapeller P, Kleinert R, Fazekas F. Tumefactive demyelinating lesions: conventional and advanced magnetic resonance imaging. Mult Scler 2005; 11:135–9.
66.van Waesberghe JH, Castelijns JA, Scheltens P, et al. Comparison of four potential MR parameters for severe tissue destruction in multiple sclerosis lesions. Magn Reson Imaging 1997; 15:155–62.
67. Ge Y, Grossman RI, Babb JS, He J, Mannon LJ. Dirty-appearing white matter in multiple sclerosis: volumetric MR imaging and magnetization transfer ratio histogram analysis. Am J Neuroradiol 2003; 24:1935–40.
68. Rovaris M, Filippi M, Falautano M, et al. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Neurology 1998; 50:1601–08.
69. van Waesberghe JH, van Buchem MA, Filippi M, et al. MR outcome parameters in multiple sclerosis: comparison of surface-based thresholding segmentation and magnetization transfer ratio histographic analysis in relation to disability (a preliminary note). Am J Neuroradiol 1998; 19:1857–62.
70. Filippi M, Rocca MA, Horsfield MA, Comi G. A one year study of new lesions in multiple sclerosis using monthly gadolinium enhanced MRI: correlations with changes of T2 and magnetization transfer lesion loads, J Neurol Sci 1998; 158:203–8.
71. Rovaris M, Filippi M, Calori G, et al. Intra-observer reproducibility in measuring new putative MR markers of demyelination and axonal loss in multiple sclerosis: a comparison with conventional T2-weighted images. J Neurol 1997; 244:266–70.
72. Iannucci G, Rovaris M, Giacomotti L, Comi G, Filippi M. Correlation of multiple sclerosis measures derived from T2-weighted, T1-weighted, magnetization transfer, and diffusion tensor MR imaging. Am J Neuroradiol 2001; 22:1462–7.
73. Filippi M, Tortorella C, Rovaris M, et al. Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry 2000; 68:157–61.
74. Rovaris M, Bozzali M, Santuccio G, et al. In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 2001; 124:2540–9.
75. Filippi M, Inglese M, Rovaris M, et al. Magnetization transfer imaging to monitor the evolution of MS: a 1-year follow-up study. Neurology 2000; 55:940–6.
76. Iannucci G, Tortorella C, Rovaris M, Sormani MP, Comi G, Filippi M. Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. Am J Neuroradiol 2000; 21:1034–8.
77. Filippi M, Iannucci G, Tortorella C, et al. Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI. Neurology 1999; 52:588–94.
78. Codella M, Rocca MA, Colombo B, Rossi P, Comi G, Filippi M. A preliminary study of magnetization transfer and diffusion tensor MRI of multiple sclerosis patients with fatigue. J Neurol 2002; 249:535–7.
79. Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M. Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain 2006; 129:2620–7.
80. Rocca MA, Falini A, Colombo B, Scotti G, Comi G, Filippi M. Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol 2002; 51:330–9.
81. Filippi M, Rocca MA. Cortical reorganisation in patients with MS. J Neurol Neurosurg Psychiatry 2004; 75:1087–9.
82. Filippi M, Rocca MA. Functional MR imaging in multiple sclerosis. Neuroimaging Clin N Am 2009; 19:59–70.
83. Adams CW. Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 1977; 33:15–20.
84. Allen IV, McKeown SR. A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 1979; 41:81–91.
85. Arstila AU, Riekkinen P, Rinne UK, Laitinen L. Studies on the pathogenesis of multiple sclerosis. Participation of lysosomes on demyelination in the central nervous system white matter outside plaques. Eur Neurol 1973; 9:1–20.
86. Bjartmar C, Kinkel RP, Kidd G, Rudick RA, Trapp BD. Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 2001; 57:1248–52.
87. Rovaris M, Filippi M. The value of new magnetic resonance techniques in multiple sclerosis. Curr Opin Neurol 2000; 13:249–54.
88. Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S. Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis. Mult Scler 2002; 8:479–84.
89. De Stefano N, Narayanan S, Francis SJ, et al. Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability, Arch Neurol 2002; 59:1565–71.
90. Filippi M, Rocca MA, Minicucci L, et al. Magnetization transfer imaging of patients with definite MS and negative conventional MRI. Neurology 1999; 52:845–8.
91. Tortorella C, Viti B, Bozzali M, et al. A magnetization transfer histogram study of normal-appearing brain tissue in MS. Neurology 2000; 54:186–93.
92. Traboulsee A, Dehmeshki J, Peters KR, et al. Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities. Mult Scler 2003; 9:566–73.
93. Mezzapesa DM, Rocca MA, Falini A, et al. A preliminary diffusion tensor and magnetization transfer magnetic resonance imaging study of early-onset multiple sclerosis. Arch Neurol 2004; 61:366–8.
94. Filippi M, Rocca MA, Falini A, et al. Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 2002; 15:537–46.
95. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2001; 70:311–17.
96. Ge Y, Grossman RI, Udupa JK, Babb JS, Mannon LJ, McGowan JC. Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis. J Comput Assist Tomogr 2002; 26:62–8.
97. Dehmeshki J, Chard DT, Leary SM, et al. The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study. J Neurol 2003; 250:67–74.
98. Santos AC, Narayanan S, de Stefano N, et al. Magnetization transfer can predict clinical evolution in patients with multiple sclerosis. J Neurol 2002; 249:662–8.
99. Inglese M, DeStefano N, Pagani E, et al. Quantification of brain damage in cerebrotendinous xanthomatosis with magnetization transfer MR imaging Am J Neuroradiol 2003; 24:495–500.
100. Filippi M, Rocca MA, Moiola L, et al. MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica. Neurology 1999; 53:1705–10.
101. Agosta F, Rocca MA, Benedetti B, Capra R, Cordioli C, Filippi M. MR imaging assessment of brain and cervical cord damage in patients with neuroborreliosis. Am J Neuroradiol 2006; 27:892–4.
102. Brownell B, Hughes JT. The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 1962; 25:315–20.
103. Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis, Brain 1999; 122 (1):17–26.
104. Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 2001; 50:389–400.
105. Ge Y, Grossman RI, Udupa JK, Babb JS, Kolson DL, McGowan JC. Magnetization transfer ratio histogram analysis of gray matter in relapsing–remitting multiple sclerosis. Am J Neuroradiol 2001; 22:470–5.
106. Fernando KT, Tozer DJ, Miszkiel KA, et al. Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2005; 128:2911–25.
107. Ramio-Torrenta L, Sastre-Garriga J, Ingle GT, et al. Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study. J Neurol Neurosurg Psychiatry 2006; 77:40–5.
108. De Stefano N, Battaglini M, Stromillo ML, et al. Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis. Brain 2006; 129:2008–16.
109. Oreja-Guevara C, Charil A, Caputo D, Cavarretta R, Sormani MP, Filippi M. Magnetization transfer magnetic resonance imaging and clinical changes in patients with relapsing–remitting multiple sclerosis. Arch Neurol 2006; 63:736–40.
110. Hayton T, Furby J, Smith KJ, et al. Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis. J Neurol 2009; 256:427–435.
111. Amato MP, Portaccio E, Stromillo ML, et al. Cognitive assessment and quantitative magnetic resonance metrics can help to identify benign multiple sclerosis, Neurology 2008; 71:632–8.
112. Codella M, Rocca MA, Colombo B, Martinelli-Boneschi F, Comi G, Filippi M. Cerebral grey matter pathology and fatigue in patients with multiple sclerosis: a preliminary study. J Neurol Sci 2002; 194:71–4.
113. Davies GR, Altmann DR, Rashid W, et al. Emergence of thalamic magnetization transfer ratio abnormality in early relapsing–remitting multiple sclerosis. Mult Scler 2005; 11:276–81.
114. Khaleeli Z, Altmann DR, Cercignani M, Ciccarelli O, Miller DH, Thompson AJ. Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis. Arch Neurol 2008; 65:1454–9.
115. Audoin B, Fernando KT, Swanton JK, Thompson AJ, Plant GT, Miller DH. Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis. Brain 2006; 129:1031–9.
116. Khaleeli Z, Cercignani M, Audoin B, Ciccarelli O, Miller DH, Thompson AJ. Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability. Neuroimage 2007; 37:253–61.
117. Rocca MA, Agosta F, Mezzapesa DM, et al. Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica. Neurology 2004; 62:476–8.
118. Dehmeshki J, Ruto AC, Arridge S, Silver NC, Miller DH, Tofts PS. Analysis of MTR histograms in multiple sclerosis using principal components and multiple discriminant analysis. Magn Reson Med 2001; 46:600–9.
119. Kalkers NF, Hintzen RQ, van Waesberghe JH, et al. Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy. J Neurol Sci 2001; 184:155–62.
120. Rovaris M, Agosta F, Sormani MP, et al. Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study. Brain 2003; 126:2323–32.
121. Rovaris M, Holtmannspotter M, Rocca MA, et al. Contribution of cervical cord MRI and brain magnetization transfer imaging to the assessment of individual patients with multiple sclerosis: a preliminary study. Mult Scler 2002; 8: 52–8.
122.van Buchem MA, Grossman RI, Armstrong C, et al. Correlation of volumetric magnetization transfer imaging with clinical data in MS. Neurology 1998; 50:1609–17.
123. Iannucci G, Minicucci L, Rodegher M, Sormani MP, Comi G, Filippi M. Correlations between clinical and MRI involvement in multiple sclerosis: assessment using T(1), T(2) and MT histograms. J Neurol Sci 1999; 171:121–9.
124. Comi G, Rovaris M, Falautano M, et al. A multiparametric MRI study of frontal lobe dementia in multiple sclerosis. J Neurol Sci 1999; 171:135–44.
125. Bozzali M, Rocca MA, Iannucci G, Pereira C, Comi G, Filippi M. Magnetization-transfer histogram analysis of the cervical cord in patients with multiple sclerosis. Am J Neuroradiol 1999; 20:1803–8.
126. Hickman SJ, Hadjiprocopis A, Coulon O, Miller DH, Barker GJ. Cervical spinal cord MTR histogram analysis in multiple sclerosis using a 3D acquisition and a B-spline active surface segmentation technique. Magn Reson Imaging 2004; 22:891–5.
127. Boorstein JM, Moonis G, Boorstein SM, Patel YP, Culler AS. Optic neuritis: imaging with magnetization transfer. AJR Am J Roentgenol 1997; 169:1709–12.
128. Vinogradov E, Degenhardt A, Smith D, et al. High-resolution anatomic, diffusion tensor, and magnetization transfer magnetic resonance imaging of the optic chiasm at 3T. J Magn Reson Imaging 2005; 22:302–306.
129. Silver NC, Barker GJ, Losseff NA, et al. Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis. Neuroradiology 1997; 39:441–445.
130. Lycklama a Nijeholt GJ, Castelijns JA, Lazeron RH, et al. Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability. J Neuroimaging 2000; 10:67–72.
131. Filippi M, Bozzali M, Horsfield MA, et al. A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology 2000; 54:207–13.
132. Rovaris M, Gallo A, Riva R, et al. An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS. Neurology 2004; 63:584–5.
133. Zackowski KM, Smith SA, Reich DS, et al. Sensorimotor dysfunction in multiple sclerosis and column-specific magnetization transfer-imaging abnormalities in the spinal cord. Brain 2009; 132:1200–9.
134. Rovaris M, Bozzali M, Santuccio G, et al. Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis. J Neurol Neurosurg Psychiatry 2000; 69:723–7.
135. Rocca MA, Filippi M, Herzog J, Sormani MP, Dichgans M, Yousry TA. A magnetic resonance imaging study of the cervical cord of patients with CADASIL. Neurology 2001; 56:1392–4.
136. Inglese M, Ghezzi A, Bianchi S, et al. Irreversible disability and tissue loss in multiple sclerosis: a conventional and magnetization transfer magnetic resonance imaging study of the optic nerves. Arch Neurol 2002; 59:250–5.
137. Melzi L, Rocca MA, Marzoli SB, et al. A longitudinal conventional and magnetization transfer magnetic resonance imaging study of optic neuritis. Mult Scler 2007; 13:265–8.
138. Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 2009; 5:256–66.
139. Ropele S, Filippi M, Valsasina P, et al. Assessment and correction of B1-induced errors in magnetization transfer ratio measurements. Magn Reson Med 2005; 53:134–40.
140. Filippi M, Dousset V, McFarland HF, Miller DH, Grossman RI. Role of magnetic resonance imaging in the diagnosis and monitoring of multiple sclerosis: consensus report of the White Matter Study Group. J Magn Reson Imaging 2002; 15:499–504.
141. Horsfield MA, Barker GJ, Barkhof F, Miller DH, Thompson AJ, Filippi M. Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis. J Magn Reson Imaging 2003; 17:389–97.
142. Samson RS, Wheeler-Kingshott CA, Symms MR, Tozer DJ, Tofts PS. A simple correction for B1 field errors in magnetization transfer ratio measurements, Magn Reson Imaging 2006; 24:255–263.
143. Richert ND, Ostuni JL, Bash CN, Duyn JH, McFarland HF, Frank JA. Serial whole-brain magnetization transfer imaging in patients with relapsing–remitting multiple sclerosis at baseline and during treatment with interferon beta-1b. Am J Neuroradiol 1998; 19:1705–13.
144. Richert ND, Ostuni JL, Bash CN, Leist TP, McFarland HF, Frank JA. Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult Scler 2001; 7:49–58.
145. Kita M, Goodkin DE, Bacchetti P, Waubant E, Nelson SJ, Majumdar S. Magnetization transfer ratio in new MS lesions before and during therapy with IFNbeta-1a. Neurology 2000; 54:1741–5.
146. Fox RJ, Fisher E, Tkach J, Lee JC, Cohen JA, Rudick RA. Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications. Mult Scler 2005; 11:140–5.
147. Inglese M, van Waesberghe JH, Rovaris M, et al. The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS. Neurology 2003; 60:853–60.
148. Filippi M, Rocca MA, Pagani E, et al. European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis. Arch Neurol 2004; 61:1409–12.
149. Rocca MA, Agosta F, Sormani MP, et al. A three-year, multi-parametric MRI study in patients at presentation with CIS. J Neurol 2008; 255:683–91.
150. Rovaris M, Judica E, Sastre-Garriga J, et al. Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis Mult Scler 2008; 14:455–64.
151. Mesaros S, Rocca M, Sormani M, et al. Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study, Mult Scler 2010; 16:325–31.
152. Van Den Elskamp IJ, Knol DL, Vrenken H, et al. Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis, Mult Scler 2010; 16:660–9.
153. Chen JT, Kuhlmann T, Jansen GH, et al. Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion. Neuroimage 2007; 36:1152–8.
154. Giacomini PS, Levesque IR, Ribeiro L, et al. Measuring demyelination and remyelination in acute multiple sclerosis lesion voxels. Arch Neurol 2009; 66:375–81.
155. Mainero C, De Stefano N, Iannucci G, et al. Correlates of MS disability assessed in vivo using aggregates of MR quantities. Neurology 2001; 56:1331–4.