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Spinal Cord in Motor Neuron Diseases Using a Multi-Parametric MRI Approach

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Spinal Cord in Motor Neuron Diseases Using a Multi-Parametric MRI Approach Université Pierre et Marie Curie Cerveau Cognition Comportement Laboratoire d’Imagerie Biomédicale / Systèmes Dynamiques Anatomo-Fonctionnels chez l’Homme Thèse de Doctorat en Neurosciences Présentée par Mohamed-Mounir EL MENDILI Analysis of the structural integrity of the spinal cord in motor neuron diseases using a multi-parametric MRI approach Dirigée par Véronique MARCHAND-PAUVERT et Pierre-François PRADAT Présentée et soutenue le 13 Décembre 2016 devant le jury composé de Devant un jury composé de : M. Peter BEDE (PU-PH) Trinity College Dublin, Irland Rapporteur Mme. Virginie CALLOT (DR) Aix-Marseille Université Rapporteur M. Philippe CORCIA (PU-PH) Université François-Rabelais, Tours Examinateur M. Stéphane LEHERICY (PU-PH) Université Paris VI Examinateur Mme. Véronique MARCHAND-PAUVERT (DR) Université Paris VI Directeur de thèse M. Pierre-Francois PRADAT (PH) Université Paris VI Co-directeur de thèse This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. À tous les patients atteints d’une des maladies du motoneurone Contents Contents ..................................................................................................................................... i Remerciements .................................................................................................................... iii List of Tables .......................................................................................................................... iv List of Figures ......................................................................................................................... v Glossary ................................................................................................................................... vi Abstract ................................................................................................................................. vii Publications ........................................................................................................................... ix Articles arising from this work ............................................................................................................ ix Additional contributions ......................................................................................................................... x 1. Introduction ....................................................................................................................... 1 2. Background ......................................................................................................................... 2 Motor neuron diseases ..................................................................................................................... 2 Historical setting ......................................................................................................................................... 2 Amyotrophic lateral sclerosis ............................................................................................................... 3 Spinal muscular atrophy ...................................................................................................................... 14 Spinal cord MRI ............................................................................................................................ 19 Principals of MRI ...................................................................................................................................... 19 Challenges ................................................................................................................................................... 20 Clinical setting ........................................................................................................................................... 24 Research setting ....................................................................................................................................... 25 Advanced MRI ........................................................................................................................................... 26 3. Objectives ......................................................................................................................... 38 4. Results ............................................................................................................................... 39 Methodological studies .............................................................................................................. 39 Study 1 - Validation of a semi-automated spinal cord segmentation method .............. 39 Study 2 - Fast and accurate semi-automated segmentation method of spinal cord MR images at 3T applied to the construction of a cervical spinal cord template ................ 48 Multi-parametric MRI studies in MND .................................................................................. 71 - i - Study 3 - Electrophysiological and spinal imaging evidence for sensory dysfunction in amyotrophic lateral sclerosis ........................................................................................................ 71 Study 4 - Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis ............................................................................................................. 83 Study 5 – Cervical spinal cord atrophy profile in adult SMN1-linked SMA .................... 92 5. Discussion ...................................................................................................................... 106 Methodological developments ............................................................................................. 106 Multi-parametric MRI studies in MND ............................................................................... 108 Perspectives ............................................................................................................................... 111 Annex A ................................................................................................................................ 113 Annex B ................................................................................................................................ 124 References .......................................................................................................................... 142 - ii - Remerciements Le Papillon et la Tulipe Sur la tulipe, un papillon se pose. « D’où vient, dit-il, la douce odeur Qui s’éxhale aujourd’hui de ta charmante fleur ? » La tulipe répond : « C’est que je suis éclose À coté d’une rose. » Pour acquérir politesse et bonté, Fréquentons les meilleurs de la société. Bataille (Frédéric). Poète, né à Mandeure (Doubs) en 1850. Je souhaire remercier à travers cette fable tous les meilleurs de la société que j’ai pu fréquenter durant toutes ces 7 dernières années passées dans la recherche scientifique aux : LIF, LIB, CENIR, ICM, Service de Neuroradiologie, Département des Maladie du Système Nerveux et l’IRME. Je suouhaite aussi remercier les meilleurs de la société que j’ai pu fréquenter en dehors de l’envirronement de la recherche scientifique tout au long de ces 16 dernières années d’immigration à Paris, Hambourg, Madrid, Quito, Montréal, Grenoble, Strasbourg, Tours et Nantes. Je remercie particulierement mes anciens et actuels maîtres de la recherche scientifique : Olivier David, Habib Benali, Julien Cohen-Adad, Serge Rossignole et Véronique Marchand-Pauvert. Je remerci infiniment mon maître et ami Pierre-François Pradat pour son soutien scientifique et moral, pour ses encouragements et particulièrement pour sa confiance en mes idées même celles des plus folles, tu es l’un des meilleurs de la société que j’ai fréquenté et que je compte bien continuer à fréquenter. Je remercie mes étudiants et d’une certaine manière mes maîtres aussi : Noémie, Brice et Raphaël. Je remercie mes amis et/ou amours pour leur soutien sans faille tout au long de cette thèse et au- delà : Tania, Lala Salma et Sidi Waldo, Sarita, Nadjia et Raphaël, Clara, Mathieu, Emma et Eric. Enfin, je remerci ma famille, ma mère, mes deux frères et mon plus grand maître, mon père. - iii - List of Tables Table 1. Principal characteristics of ALS phenotypes ............................................................. 10 Table 2. The SMN2 gene copy number and the related motor performance in SMA ...................... 15 Table 3. The spin density and the relaxation time in some tissues ............................................. 19 Table 4. Detected spinal cord MRI abnormalities in “mimic” MND .......................................... 25 Table 5. Correlations between DTI indexes and white matter microstructures... .......................... 35 Tableau 1 Tableau 2 Tableau 3 Tableau 4 Tableau 5 - iv - List of Figures Figure 1. The human motor system ................................................................................... 4 Figure 2. The worldwide crude incidence distribution of ALS ................................................... 5 Figure 3. Patterns of motor involvement in different ALS phenotypes ......................................... 8 Figure 4. Cervical spine MRI abnormalities in a case of cervical spondylotic myelopathy ................. 13 Figure 5. Overview of non-neuromuscular systemic pathology in SMA ...................................... 15 Figure 6. A diagnostic algorithm for SMA ........................................................................
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