A. Mackay, K. Whittall, J. Adler, D. Li, D. Paty et al., In vivo visualization of myelin water in brain by magnetic resonance, Magn Reson Med Off J Soc Magn Reson Med Soc Magn Reson Med, vol.31, issue.6, pp.673-677, 1994.

A. Gass, G. J. Barker, and D. Kidd, Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis, Ann Neurol, vol.36, issue.1, pp.62-67, 1994.

M. A. Rocca, G. Mastronardo, M. Rodegher, G. Comi, and M. Filippi, Long-term changes of magnetization transferderived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis, Am J Neuroradiol, vol.20, issue.5, pp.821-827, 1999.

K. Schmierer, F. Scaravilli, D. R. Altmann, G. J. Barker, and D. H. Miller, Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain, Ann Neurol, vol.56, issue.3, pp.407-415, 2004.

M. Filippi, A. Campi, and V. Dousset, A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis, Neurology, vol.45, issue.3, pp.478-482, 1995.

G. Varma, G. Duhamel, C. De-bazelaire, and D. C. Alsop, Magnetization transfer from inhomogeneously broadened lines: A potential marker for myelin, Magn Reson Med, vol.73, issue.2, pp.614-622, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01414328

G. Varma, O. M. Girard, V. H. Prevost, A. Grant, G. D. Duhamel et al., Interpretation of magnetization transfer, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01414326

V. H. Prevost, O. M. Girard, S. Mchinda, G. Varma, D. C. Alsop et al., Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time ( T 1D ) filtering, NMR Biomed, vol.30, issue.6, p.3706, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01657969

V. H. Prevost, O. M. Girard, and M. Cayre, Validation of inhomogeneous Magnetization Transfer (ihMT) as a myelin biomarker, Int Soc Magn Reson Med, p.1498, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01784676

O. M. Girard, V. H. Prevost, G. Varma, P. J. Cozzone, D. C. Alsop et al., Magnetization transfer from inhomogeneously broadened lines (ihMT): Experimental optimization of saturation parameters for human brain imaging at 1.5 Tesla, Magn Reson Med, vol.73, issue.6, pp.2111-2121, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01414354

O. M. Girard, V. Callot, and V. H. Prevost, Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications: ihMT for Spinal Cord Applications, Magn Reson Med, vol.77, issue.2, pp.581-591, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01425518

J. F. Kurtzke, Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS), Neurology, vol.33, issue.11, pp.1444-1452, 1983.

V. H. Prevost, O. M. Girard, G. Varma, D. C. Alsop, and G. Duhamel, Minimizing the effects of magnetization transfer asymmetry on inhomogeneous magnetization transfer (ihMT) at ultra-high magnetic field (11.75 T). Magn Reson Mater, Phys Biol Med, vol.29, issue.4, pp.699-709, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01425510

B. B. Avants, N. J. Tustison, G. Song, P. A. Cook, A. Klein et al., A reproducible evaluation of ANTs similarity metric performance in brain image registration, NeuroImage, vol.54, issue.3, pp.2033-2044, 2011.

M. Filippi and F. Agosta, Magnetization Transfer MRI in Multiple Sclerosis, J Neuroimaging, vol.17, pp.22-26, 2007.

A. Traboulsee, J. Dehmeshki, and K. R. Peters, Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities, Mult Scler, vol.9, issue.6, pp.566-573, 2003.

H. Vrenken, P. Pouwels, and S. Ropele, Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease, Mult Scler, vol.13, issue.6, pp.708-716, 2007.

M. Amann, A. Papadopoulou, and M. Andelova, Magnetization transfer ratio in lesions rather than normalappearing brain relates to disability in patients with multiple sclerosis, J Neurol, vol.262, issue.8, pp.1909-1917, 2015.

D. Stefano and N. , Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis, Brain, vol.129, issue.8, pp.2008-2016, 2006.

A. C. Santos, S. Narayanan, and N. De-stefano, Magnetization transfer can predict clinical evolution in patients with multiple sclerosis, J Neurol, vol.249, issue.6, pp.662-668, 2002.

N. M. Moll, A. M. Rietsch, and S. Thomas, Multiple sclerosis normal-appearing white matter: Pathology-imaging correlations, Ann Neurol, vol.70, issue.5, pp.764-773, 2011.

S. Mchinda, G. Varma, and V. H. Prevost, characterization of the power dependency regimes of inhomogeneous magnetization transfer (ihMT). Int Soc Magn Reson Med, p.3763, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01784668

. Iv and . Références,

I. Metz, S. D. Weigand, B. Popescu, J. M. Frischer, J. E. Parisi et al., Pathologic heterogeneity persists in early active multiple sclerosis lesions: Pathologic Heterogeneity in MS, Ann Neurol, vol.75, pp.728-766, 2014.

C. Lucchinetti, W. Brück, J. Parisi, B. Scheithauer, M. Rodriguez et al., Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination, Ann Neurol, vol.47, pp.707-724, 2000.

L. Bö, J. Geurts, S. J. Mörk, and P. Valk, Grey matter pathology in multiple sclerosis, Acta Neurol Scand, vol.113, pp.48-50, 2006.

M. Filippi and M. A. Rocca, MRI evidence for multiple sclerosis as a diffuse disease of the central nervous system, J Neurol, vol.252, pp.16-24, 2005.

A. Kutzelnigg, Cortical demyelination and diffuse white matter injury in multiple sclerosis, Brain, vol.128, pp.2705-2717, 2005.

M. Filippi, P. Preziosa, and M. A. Rocca, Microstructural MR Imaging Techniques in Multiple Sclerosis, Neuroimaging Clin N Am, vol.27, pp.313-346, 2017.

R. M. Henkelman, G. J. Stanisz, and S. J. Graham, Magnetization transfer in MRI: a review, NMR Biomed, vol.14, pp.57-64, 2001.

L. Turati, M. Moscatelli, A. Mastropietro, N. G. Dowell, I. Zucca et al., In vivo quantitative magnetization transfer imaging correlates with histology during de-and remyelination in cuprizone-treated mice: QUANTITATIVE MAGNETIZATION TRANSFER IMAGING IN CUPRIZONE-TREATED MICE, NMR Biomed, vol.28, pp.327-364, 2015.

M. Filippi, M. A. Rocca, G. Martino, M. A. Horsfield, and G. Comi, Magnetization transfer changes in the normal appering white matter precede the appearance of enhancing lesions in patients with multiple sclerosis, Ann Neurol, vol.43, pp.809-823, 1998.

Y. Wang, P. Sun, Q. Wang, K. Trinkaus, R. E. Schmidt et al., Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis, Brain, vol.138, pp.1223-1261, 2015.

K. Schmierer, F. Scaravilli, D. R. Altmann, G. J. Barker, and D. H. Miller, Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain, Ann Neurol, vol.56, pp.407-422, 2004.

I. M. Vavasour, C. Laule, D. Li, A. L. Traboulsee, and A. L. Mackay, Is the magnetization transfer ratio a marker for myelin in multiple sclerosis?, J Magn Reson Imaging, vol.33, pp.710-718, 2011.

A. Mackay, K. Whittall, J. Adler, D. Li, D. Paty et al., In vivo visualization of myelin water in brain by magnetic resonance, Magn Reson Med, vol.31, pp.673-680, 1994.

J. Chen, C. Zhou, L. Zhu, X. Yan, Y. Wang et al., Magnetic resonance diffusion tensor imaging for occult lesion detection in multiple sclerosis, Exp Ther Med, 2016.

C. Beaulieu, The basis of anisotropic water diffusion in the nervous system -a technical review, NMR Biomed, vol.15, pp.435-55, 2002.

O. Andersen, A. Hildeman, M. Longfils, H. Tedeholm, B. Skoog et al., Diffusion tensor imaging in multiple sclerosis at different final outcomes, Acta Neurol Scand, 2017.

A. Droby, V. Fleischer, M. Carnini, H. Zimmermann, V. Siffrin et al., The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients, NeuroImage Clin, vol.8, pp.110-116, 2015.

G. Lovas, N. Szilágyi, K. Majtényi, M. Palkovits, and S. Komoly, Axonal changes in chronic demyelinated cervical spinal cord plaques, Brain J Neurol, vol.123, issue.2, pp.308-325, 2000.

R. T. Naismith, J. Xu, N. T. Tutlam, K. Trinkaus, A. H. Cross et al., Radial diffusivity in remote optic neuritis discriminates visual outcomes, Neurology, vol.74, pp.1702-1712, 2010.

O. Ciccarelli, M. Catani, H. Johansen-berg, C. Clark, and A. Thompson, Diffusion-based tractography in neurological disorders: concepts, applications, and future developments, Lancet Neurol, vol.7, pp.715-742, 2008.

Y. Li, V. Jewells, M. Kim, Y. Chen, A. Moon et al., Diffusion tensor imaging based network analysis detects alterations of neuroconnectivity in patients with clinically early relapsingremitting multiple sclerosis: Network Analysis Detects Neuroconnectivity Alterations in Early Relapsing Remitting MS, Hum Brain Mapp, vol.34, pp.3376-91, 2013.

D. J. Rigotti, M. Inglese, I. I. Kirov, E. Gorynski, N. N. Perry et al., Two-year serial whole-brain Nacetyl-L-aspartate in patients with relapsing-remitting multiple sclerosis, Neurology, vol.78, pp.1383-1392, 2012.

R. Srinivasan, Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T, Brain, vol.128, pp.1016-1041, 2005.

K. Fernando, Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis, Brain, vol.127, pp.1361-1370, 2004.

S. Llufriu, J. Kornak, H. Ratiney, J. Oh, D. Brenneman et al., Magnetic Resonance Spectroscopy Markers of Disease Progression in Multiple Sclerosis, JAMA Neurol, vol.71, p.840, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01016575

G. Varma, G. Duhamel, C. De-bazelaire, and D. C. Alsop, Magnetization transfer from inhomogeneously broadened lines: A potential marker for myelin: Magnetization Transfer from Inhomogeneously Broadened Lines, Magn Reson Med, vol.73, pp.614-636, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01414328

O. M. Girard, V. H. Prevost, G. Varma, P. J. Cozzone, D. C. Alsop et al., Magnetization transfer from inhomogeneously broadened lines (ihMT): Experimental optimization of saturation parameters for human brain imaging at 1.5 Tesla: Optimizing Saturation Parameters for ihMT Brain Imaging at 1.5T, Magn Reson Med, vol.73, pp.2111-2132, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01414354

V. H. Prevost, O. M. Girard, S. Mchinda, G. Varma, D. C. Alsop et al., Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time ( T 1D ) filtering, NMR Biomed, vol.30, p.3706, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01657969

G. Varma, O. M. Girard, V. H. Prevost, A. K. Grant, G. Duhamel et al., Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules, J Magn Reson, vol.260, pp.67-76, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01414326

G. Varma, O. M. Girard, V. H. Prevost, A. K. Grant, G. Duhamel et al., In vivo measurement of a new source of contrast, the dipolar relaxation time, T 1 D , using a modified inhomogeneous magnetization transfer (ihMT) sequence: In Vivo Measurement of T 1D Using ihMT, Magn Reson Med, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01425505

M. Filippi and M. A. Rocca, Magnetization transfer magnetic resonance imaging of the brain, spinal cord, and optic nerve, Neurotherapeutics, vol.4, pp.401-414, 2007.

L. Fisniku, D. Altmann, M. Cercignani, D. Tozer, D. Chard et al., Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis, Mult Scler J, vol.15, pp.668-77, 2009.

R. S. Samson, M. J. Cardoso, N. Muhlert, V. Sethi, C. A. Wheeler-kingshott et al., Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups, Mult Scler J, vol.20, pp.1322-1352, 2014.

H. Vrenken, P. Pouwels, S. Ropele, D. L. Knol, J. Geurts et al., Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease, Mult Scler J, vol.13, pp.708-724, 2007.

Z. Khaleeli, D. R. Altmann, M. Cercignani, O. Ciccarelli, D. H. Miller et al., Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis, Arch Neurol, vol.65, pp.1454-1463, 2008.

M. Amann, A. Papadopoulou, M. Andelova, S. Magon, N. Mueller-lenke et al., Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis, J Neurol, vol.262, pp.1909-1926, 2015.

A. Gass, G. J. Barker, D. Kidd, J. W. Thorpe, D. Macmanus et al., Correlation of magnetization transfer ration with clinical disability in multiple sclerosis, Ann Neurol, vol.36, pp.62-69, 1994.

Z. Khaleeli, M. Cercignani, B. Audoin, O. Ciccarelli, D. H. Miller et al., Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability, NeuroImage, vol.37, pp.253-61, 2007.

A. K. Smith, S. By, B. D. Lyttle, R. D. Dortch, B. A. Box et al., Evaluating single-point quantitative magnetization transfer in the cervical spinal cord: Application to multiple sclerosis, NeuroImage Clin, vol.16, pp.58-65, 2017.

A. C. Santos, S. Narayanan, N. De-stefano, M. C. Tartaglia, S. J. Francis et al., Magnetization transfer can predict clinical evolution in patients with multiple sclerosis, J Neurol, vol.249, pp.662-670, 2002.

Z. Khaleeli, J. Sastre-garriga, O. Ciccarelli, D. H. Miller, and A. J. Thompson, Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis, J Neurol Neurosurg Amp Psychiatry, vol.78, pp.1076-82, 2007.

M. Rovaris, Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study, Brain, vol.126, pp.2323-2355, 2003.

F. Agosta, Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis, Brain, vol.129, pp.2620-2627, 2006.

J. T. Chen, D. L. Collins, H. L. Atkins, M. S. Freedman, D. L. Arnold et al., Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions, Ann Neurol, vol.63, pp.254-62, 2008.

A. Mistry, N. Mougin, O. Blazejewska, A. Pitiot, A. Retkute et al., Improved detection of focal cortical lesions using 7T magnetisation transfer imaging in patients with multiple sclerosis, Mult Scler Relat Disord, vol.3, pp.258-65, 2014.

V. H. Prevost, O. M. Girard, G. Varma, D. C. Alsop, and G. Duhamel, Minimizing the effects of magnetization transfer asymmetry on inhomogeneous magnetization transfer (ihMT) at ultra-high magnetic field (11.75 T). Magn Reson Mater, Phys Biol Med, vol.29, pp.699-709, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01425510

K. Schmierer, H. G. Parkes, P. So, S. F. An, S. Brandner et al., 4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis, Brain, vol.133, issue.9, pp.858-67, 2010.

M. K. Schindler, P. Sati, and D. S. Reich, Insights from Ultrahigh Field Imaging in Multiple Sclerosis, Neuroimaging Clin N Am, vol.27, pp.357-66, 2017.

R. Datta, V. Sethi, S. Ly, A. T. Waldman, S. Narula et al., 7T MRI Visualization of Cortical Lesions in Adolescents and Young Adults with Pediatric-Onset Multiple Sclerosis: 7T MRI in Pediatric Multiple Sclerosis, J Neuroimaging, 2017.

I. D. Kilsdonk, L. E. Jonkman, R. Klaver, S. J. Van-veluw, J. Zwanenburg et al., Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study, Brain, vol.139, pp.1472-81, 2016.

A. Minagar, M. H. Barnett, R. Benedict, D. Pelletier, I. Pirko et al., The thalamus and multiple sclerosis: Modern views on pathologic, imaging, and clinical aspects, Neurology, vol.80, pp.210-219, 2013.

M. Koini, M. Filippi, M. A. Rocca, T. Yousry, O. Ciccarelli et al., Correlates of executive functions in multiple sclerosis based on structural and functional MR imaging: insights from a multicenter study, Radiology, vol.280, pp.869-79, 2016.

O. M. Girard, V. Callot, V. H. Prevost, B. Robert, M. Taso et al., Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications: ihMT for Spinal Cord Applications, Magn Reson Med, vol.77, pp.581-91, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01425518

J. R. Plemel, W. Liu, and Y. Vw, Remyelination therapies: a new direction and challenge in multiple sclerosis, Nat Rev Drug Discov, 2017.

K. Cole, J. J. Early, and D. A. Lyons, Drug discovery for remyelination and treatment of MS, Glia, 2017.

B. V. Ineichen, P. S. Plattner, N. Good, R. Martin, M. Linnebank et al., Nogo-A Antibodies for Progressive Multiple Sclerosis, CNS Drugs, vol.31, pp.187-98, 2017.

D. E. Harlow, J. M. Honce, and A. A. Miravalle, Remyelination Therapy in Multiple Sclerosis, Front Neurol, vol.6, 2015.

, Serment d'Hippocrate

, Au moment d'être admis(e) à exercer la médecine, je promets et je jure d'être fidèle aux lois de l'honneur et de la probité

, Mon premier souci sera de rétablir, de préserver ou de promouvoir la santé dans tous ses éléments, physiques et mentaux, individuels et sociaux

, Je respecterai toutes les personnes, leur autonomie et leur volonté, sans aucune discrimination selon leur état ou leurs convictions. J'interviendrai pour les protéger si elles sont affaiblies, vulnérables ou menacées dans leur intégrité ou leur dignité. Même sous la contrainte

, Admis(e) dans l'intimité des personnes, je tairai les secrets qui me seront confiés

, J'apporterai mon aide à mes confrères ainsi qu'à leurs familles dans l'adversité

, Que les hommes et mes confrères m'accordent leur estime si je suis fidèle à mes promesses