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L’IRM de diffusion (IRMd) est une modalité d’imagerie médicale in vivo qui suscite un intérêt croissant dans la communauté de neuro-imagerie. L’information sur l’intra-structure des tissus cérébraux est apportée en complément des informations de structure issues de l’IRM structurelle (IRMs). Ces modalités d’imagerie ouvrent ainsi une nouvelle voie pour l’analyse de population et notamment pour l’étude de la maturation cérébrale humaine normale in utero. La modélisation et la caractérisation des changements rapides intervenant au cours de la maturation cérébrale est un défi actuel. Dans ce but, ce mémoire de thèse présente une chaîne de traitement complète de la modélisation spatio-temporelle de la population à l’analyse des changements de forme au cours du temps. Les contributions se répartissent sur trois points. Tout d’abord, l’utilisation de filtre à particules étendus aux modèles d’ordre supérieurs pour la tractographie a permis d’extraire des descripteurs plus pertinents chez le foetus, utilisés ensuite pour estimer les transformations géométriques entre images. Ensuite, l’emploi d’une technique de régression non-paramétrique a permis de modéliser l’évolution temporelle moyenne du cerveau foetal sans imposer d’à priori. Enfin, les changements de forme sont mis en évidence au moyen de méthodes d’extraction et de sélection de caractéristiques. / Diffusion weighted MRI (dMRI) is an in vivo imaging modality which raises a great interest in the neuro-imaging community. The intra-structural information of cerebral tissues is provided in addition to the morphological information from structural MRI (sMRI). These imaging modalities bring a new path for population studies, especially for the study in utero of the normal humanbrain maturation. The modeling and the characterization of rapid changes in the brain maturation is an actual challenge. For these purposes, this thesis memoir present a complete processing pipeline from the spatio-temporal modeling of the population to the changes analyze against the time. The contributions are about three points. First, the use of high order diffusion models within a particle filtering framework allows to extract more relevant descriptors of the fetal brain, which are then used for image registration. Then, a non-parametric regression technique was used to model the temporal mean evolution of the fetal brain without enforce a prior knowledge. Finally, the shape changes are highlighted using features extraction and selection methods.

Ce travail vise au développement d’une méthode d’inférence des fibres de la substance blanche cérébrale fondée sur l’utilisation d’une approche globale de type « verres de spins » sous contraintes anatomiques. Contrairement aux méthodes classiques reconstituant les fibres indépendamment les unes des autres, cette approche markovienne reconstruit l’ensemble des fibres dans un unique processus de minimisation d’une énergie globale dépendant de la configuration des spins (position, orientation, longueur et connexion(s)) et de leur adéquation avec le modèle local du processus de diffusion, afin d'améliorer la robustesse et la réalité anatomique des fibres reconstruites. Le travail mené dans le cadre de cette thèse a donc consisté, en plus du développement de l’algorithme de tractographie, à étudier la possibilité de le contraindre à l’aide d’a priori anatomiques provenant de l’imagerie anatomique pondérée en T1 et des nouvelles approches de microscopie par IRM de diffusion fournissant des informations de nature micro-structurelle sur le tissu. En particulier, l’algorithme a été conçu pour autoriser une forte courbure des fibres à l’approche du ruban cortical et permettre leur connexion au sommet des gyri, mais également sur leurs flancs. Le modèle NODDI (Neurite Orientation Dispersion and Density Imaging) a gagné en popularité au cours des dernières années grâce à sa compatibilité avec une utilisation en routine clinique et permet de quantifier la densité neuritique et la dispersion angulaire des axones. Une forte dispersion traduit l’existence de populations de fibres d’orientations différentes ou une forte courbure d’un même faisceau de fibres au sein d'un voxel. Elle est donc exploitée pour relâcher la contrainte de faible courbure à proximité du cortex cérébral dans notre approche de tractographie globale lorsque cette dispersion angulaire est forte, permettant aux fibres de s'orienter par rapport à la normale locale au cortex. Cette contrainte est en revanche supprimée si la dispersion angulaire reste faible, indiquant une trajectoire à plus faible courbure, à l’instar des fibres se projetant dans le fond du gyrus ou des fibres en U. Les performances de cette nouvelle approche de tractographie sous contraintes anatomiques ont été évaluées à partir de données simulées, et ont été testées sur des données IRM post-mortem de très haute résolution et sur des données IRM in vivo de résolution millimétrique. En parallèle de ce développement méthodologique, une étude des corrélats locaux-régionaux de la densité neuritique et de l’activation cérébrale à la surface du cortex a été réalisée. L'étude a été menée sur la cohorte de sujets sains scannés dans le cadre du projet européen CONNECT dotée de données anatomiques, de diffusion et fonctionnelles reposant sur l’utilisation de paradigmes explorant en particulier les réseaux de la motricité, du langage et de la vision. Les données anatomiques ont permis d’extraire la surface piale et une parcellisation surfacique du cortex de chaque individu, les données de diffusion ont permis l’évaluation des cartographies individuelles de la densité neuritique au sein du ruban cortical et les données fonctionnelles du phénomène BOLD (Blood Oxygen Level Dependent) ont permis le calcul des cartographies individuelles des z-scores du modèle linéaire général pour différents contrastes. Une colocalisation des maxima de la densité neuritique et des pics d'activation a été observée, pouvant être interprétée comme une augmentation de la densité neuritique au sein des réseaux fonctionnels afin d'en améliorer l'efficacité. L’étude a également corroboré la latéralisation du réseau fonctionnel du langage et de la motricité, en accord avec la latéralisation de la population scannée tandis qu'une augmentation de la densité neuritique dans le cortex visuel droit a été observée pouvant être corrélée à des résultats d’étude de l’attention visuo-spatiale reportée dans la littérature chez le primate non-humain. / This work aims at developing a method inferring white matter fibers reconstructed using a global spin-glass approach constrained by anatomical prior knowledge. Unlike usual methods building fibers independently from one another, our markovian approach reconstructs the whole tractogram in an unique process by minimizing the global energy depending on the spin glass configuration (position, orientation, length and connection(s)) and the match with the local diffusion process in order to increase the robustness and the accuracy of the algorithm and the anatomical reliability of the reconstructed fibers. Thus, the work done during this PhD, along with the development of the global tractography algorithm, consisted in studying the feasibility of the anatomical prior knowledge integration stemming from the T1 weighted MRI and from new diffusion MRI microstructure approaches providing microstructural information of the surrounding tissue. In particular, the algorithm was built to allow a high fiber curvature when getting closer to the cortical ribbon and thus enabling the connection not only at the end of the gyri but also on their sides. The NODDI (Neurite Orientation Dispersion and Density Imaging) model has become more and more popular during the past years thanks to its capability to be used in clinical routine and allows to quantify neurite density and axons angular dispersion. A high dispersion means the existence of different fibers population or a high curvature of a fascicle within a voxel. Thus, the orientation dispersion has been used in our global tractography framework to release the curvature constraint near the cerebral cortex when the angular dispersion is high, allowing fibers to orientate collinear to the local normal to the cortical surface. However, this constraint is removed if the angular dispersion stays low, meaning a low curvature fiber trajectory following the example of the fibers projecting to the end of a gyrus or the U-fibers. The performances of this new tractography approach constrained by anatomical prior knowledge have been evaluated on simulated data, and tested on high resolution post-mortem MRI acquisitions and millimetric resolution in vivo MRI acquisitions. In parallel of this methodological development, a study about local-regional correlations between neurite density and cerebral activation on the cortical surface has been made. This study has been conducted on the healthy volunteers cohort scanned in the frame of the European CONNECT project including anatomical, diffusion and functional data. The anatomical data has been used to extract the pial surface and an individual parcellation on the cortical surface for each volunteer, the diffusion data has been used to evaluate the individual maps of neurite density within the cortical ribbon and the functional data from the BOLD (Blood Oxygen Level Dependent) effect has been used to calculate the individual z-scores of the general linear model for specific contrasts investigating the motor, language and visual networks. A co-localization of neurite density and activation peaks has been observed, which might indicate an increase of the neurite density within functional networks in order to increase its efficiency. This study also corroborates the lateralization of the language functional network and the motor one, in good agreement with the population lateralization, while an increase of the neurite density in the visual cortex has been observed which might be correlated to the results of visuo-spatial attention studies described in the literature on the non-human primate.

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).