E. Leray, J. Yaouanq, E. L. Page, M. Coustans, and D. Laplaud, Evidence for a two-stage disability progression in multiple sclerosis, Brain, vol.133, pp.1900-1913, 2010.

L. Steinman, Multiple sclerosis: A two-stage disease, Nature Immunology, vol.2, pp.762-764, 2001.

C. Confavreux, S. Vukusic, and P. Adeleine, Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process, Brain, vol.126, pp.770-82, 2003.
URL : https://hal.archives-ouvertes.fr/hal-00427394

A. Scalfari, A. Neuhaus, A. Degenhardt, G. Rice, and P. Muraro, The natural history of multiple sclerosis, a geographically based study 10: Relapses and long-term disability, Brain, vol.133, pp.1914-1943, 2010.

D. Miller, F. Barkhof, X. Montalban, A. Thompson, and M. Filippi, Clinically isolated syndromes suggestive of multiple sclerosis, part 2: Non-conventional MRI, recovery processes, and management, The Lancet Neurology, vol.4, pp.341-348, 2005.

J. Marriott, J. Miyasaki, G. Gronseth, O. Connor, and P. , Evidence report: The efficacy and safety of mitoxantrone (no-vantrone) in the treatment of multiple sclerosis: Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology, Neurology, vol.74, p.14631470, 2010.

E. Fox, Management of worsening multiple sclerosis with mitoxantrone: A review, clinical therapeutics. Neu-rology, vol.28, p.461474, 2006.

A. Compston and A. Coles, Multiple sclerosis, Lancet, vol.3722, pp.1502-1517, 2001.
URL : https://hal.archives-ouvertes.fr/hal-00996686

B. Trapp, J. Peterson, R. Ransohoff, R. Rudick, and S. Mork, Axonal transection in the lesions of multiple sclerosis, New England Journal Medicine, vol.338, pp.278-285, 1998.

A. Bitsch, J. Schuchartdt, S. Bunkowski, T. Kuhlmann, and W. Brueck, Acute axonal injury in multiple sclerosisfvf. correlation with demyelination and inammation, Brain, vol.123, pp.1174-1183, 2000.

F. Aboul-enein, P. Weiser, R. Hoeftberger, H. Lassmann, and M. Bradl, Transient axonal injury in the absence of demyelination: A correlate of clinical disease in acute experimental autoimmune encephalomyelitis, Acta Neuropathology, vol.111, pp.539-586, 2006.

K. Smith, R. Kapoor, S. Hall, and M. Davies, Electrically active axons degenerate when exposed to nitric oxide, Annals of Neurology, vol.49, pp.470-476, 2001.
DOI : 10.1002/ana.96.abs

E. Redford, R. Kapoor, and K. Smith, Nitric oxide donors reversibly block axonal conduction: Demyelinated axons are especially susceptible, Brain, vol.120, pp.2149-2157, 1997.
DOI : 10.1093/brain/120.12.2149
URL : https://academic.oup.com/brain/article-pdf/120/12/2149/17862027/1202149.pdf

H. Lassman, Axonal and neuronal pathology in multiple sclerosis: what have we learnt from animal models, Experimental neurology, vol.225, pp.2-8, 2010.

B. Kornek and H. Lassmann, Axonal pathology in multiple sclerosis. A historical note, Brain pathology, vol.9, pp.651-656, 1999.

V. Dousset, B. Doche, K. Petry, B. Brochet, and C. Delalande, Correlation between clinical status and macrophage activity imaging in the central nervous system of rats, Academic Radiology, vol.9, pp.156-165, 2002.

V. Dousset, B. Brochet, M. Deloire, L. Lagoarde, and B. Barroso, MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium, American Journal of Neuroradiology, vol.27, pp.1000-1005, 2006.

T. Tourdias, S. Roggerone, M. Filippi, M. Kanagaki, and M. Rovaris, Assessment of disease activity in multiple sclerosis phenotypes with combined gadolinium-and superparamagnetic iron oxide-enhanced MR imaging, Radiology, vol.264, pp.225-233, 2012.

M. Vellinga, R. Oude-engberink, A. Seewann, P. Pouwels, and M. Wattjes, Pluriformity of inammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement, Brain, vol.131, pp.800-807, 2008.

M. Van-walderveen, W. Kamphorst, P. Scheltens, J. Van-waesberghe, and R. Ravid, Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis, Neurology, vol.50, pp.1282-1288, 1998.

M. Van-walderveen, F. Barkhof, O. Hommes, C. Polman, and H. Tobi, Correlating MRI and clinical disease activity in multiple sclerosis: Relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images, Neurology, vol.454, p.16841690, 1995.

L. Truyen, J. Van-waesberghe, M. Van-walderveen, B. Van-oosten, and C. Polman, Accumulation of hypointense lesions (''black holes'') on T1 spinecho MRI correlates with disease progression in multiple sclerosis, Neurology, vol.47, pp.1469-1476, 1996.

M. Filippi, M. Horsfield, S. Morrissey, D. Macmanus, and P. Rudge, Quantitative brain lesion load predicts the course of CIS, Neurology, vol.44, pp.635-641, 1994.

P. Brex, O. Ciccarelli, J. O'riordan, M. Sailer, and A. Thompson, A longitudinal study of abnormalities on MRI and disability from multiple sclerosis, New England Journal of Medicine, vol.346, pp.158-164, 2002.

C. Polman, S. Reingold, G. Edan, M. Filippi, and H. Hartung, Diagnostic criteria for multiple sclerosis: 2005 revisions to the McDonald Criteria, Annals of Neurology, vol.58, pp.840-846, 2005.
DOI : 10.1002/ana.22366
URL : http://onlinelibrary.wiley.com/doi/10.1002/ana.22366/pdf

J. Kurtzke, Rating neurologic impairment in multiple sclerosis: An expanded disability status scale, Neurology, vol.33, pp.1444-1452, 1983.
DOI : 10.1212/wnl.33.11.1444
URL : http://www.neurology.org/content/33/11/1444.full.pdf

W. Mcdonald, A. Compston, G. Edan, D. Goodkin, and H. Hartung, Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis, Annals of Neurology, vol.502, pp.121-127, 2001.

P. Brex, K. Miszkiel, J. O'riordan, G. Plant, and I. Moseley, Assessing the risk of early MS in patients with clinically isolated syndromes the role of followup MRI, Journal of Neurological Neurosurgery and Psychiatry, vol.70, pp.390-393, 2001.

F. Barkhof, J. Waesberghe, M. Filippi, T. Yousry, and D. Miller, T1 hypointense lesions in secondary progressive multiple sclerosis: effet of interferon beta-1b treatment, Brain, vol.124, pp.1396-1402, 2001.
DOI : 10.1093/brain/124.7.1396
URL : https://academic.oup.com/brain/article-pdf/124/7/1396/802912/1241396.pdf

S. Medinria and . Page, INRIA, 2013.

F. Maes, A. Collignon, D. Vandermeulen, G. Marchal, and P. Suetens, Multimodality image registration by maximization of mutual information, IEEE Transactions on Medical Imaging, vol.16, pp.187-198, 1997.

V. Haermae, J. Virtanen, R. Maekelae, A. Happonen, and J. Mpindi, A comprehensive panel of three-dimensional models for studies of prostate cancer growth, invasion and drug responses, PLoS One, vol.5, pp.245-267, 2010.

M. Reuter, F. Wolter, and N. Peinecke, Laplace-Beltrami spectra as shape-DNA of surfaces, CAD, vol.38, pp.342-366, 2006.

R. Duda, P. Hart, and D. Stork, , 2000.

L. Zelnik-manor and P. Perona, Self-tuning spectral clustering, vol.17, 2004.

U. Maulik and S. Bandyopadhyay, Performance evaluation of clustering algorithms, IEEE Transactions on Pattern Analysis and Machine Intelligence, vol.24, pp.1650-1654, 2002.

J. Dunn, A fuzzy relative of the ISODATA process and its use in detecting compact well-separated clusters, Journal of Cybernetics, vol.3, pp.32-57, 1973.

T. Calinski and J. Harabasz, A dendrite method for cluster analysis, Communicational Statistics, vol.3, pp.1-27, 1974.

R. Tibshirani, G. Walther, and T. Hastie, Estimating the number of clusters in a dataset via the gap statistic, Journal of the Royal Statistics Society, vol.63, pp.411-423, 2001.

J. Shi and J. Malik, Normalized cuts and image segmentation, IEEE Transactions on Pattern Analysis and Machine Intelligence, vol.22, pp.888-905, 2000.

A. Ng, M. Jordan, and Y. Weiss, On spectral clustering: Analysis and an algorithm, vol.14, pp.224-236, 2001.

J. Bezdek and N. Pal, Some new indexes of cluster validity, IEEE Transaction on Syst Man and Cybernetics, vol.28, pp.301-315, 1998.

R. Steel and J. Torrie, Principles and procedures of statistics, vol.70, pp.187-287, 1960.

P. Molyneux, M. Filippi, F. Barkhof, C. Gasperini, and T. Yousry, Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis, Annals of Neurology, vol.43, pp.332-339, 1998.

E. Gokcay and J. Principe, Information theoretic clustering, IEEE Transactions on Pattern Analysis and Machine Intelligence, vol.24, pp.158-71, 2002.

M. Bartlett, A note on multiplying factors for various chi squared approximations, Journal of the Royal Statistics Society, vol.16, pp.296-298, 1954.

T. Nichols and A. Holmes, Nonparametric permutation tests for functional neuroimaging: A primer with examples, Human Brain Mapping, vol.15, pp.1-25, 2002.

M. Smith, L. Stone, P. Albert, J. Prank, and R. Martin, Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions, Annals of Neurology, vol.33, pp.480-489, 1993.

V. Anderson, N. Fox, and D. Miller, Magnetic resonance imaging measures of brain atrophy in multiple sclerosis, Journal of Magnetic Resonance Imaging, vol.23, pp.605-618, 2006.