Volumetric and microstructural abnormalities of the amygdala in focal epilepsy with varied levels of SUDEP risk

Although the mechanisms of sudden unexpected death in epilepsy (SUDEP) are not yet well understood, generalised- or focal-to-bilateral tonic-clonic seizures (TCS) are a major risk factor. Previous studies highlighted alterations in structures linked to cardio-respiratory regulation; one structure, the amygdala, was enlarged in people at high risk of SUDEP and those who subsequently died. We investigated volume changes and the microstructure of the amygdala in people with epilepsy at varied risk for SUDEP since that structure can play a key role in triggering apnea and mediating blood pressure. The study included 53 healthy subjects and 143 patients with epilepsy, the latter separated into two groups according to whether TCS occur in years before scan. We used amygdala volumetry, derived from structural MRI, and tissue microstructure, derived from diffusion MRI, to identify differences between the groups. The diffusion metrics were obtained by fitting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. The analyses were performed at the whole amygdala level and at the scale of amygdaloid nuclei. Patients with epilepsy showed larger amygdala volumes and lower neurite density indices (NDI) than healthy subjects; the left amygdala volumes were especially enhanced. Microstructural changes, reflected by NDI differences, were more prominent on the left side and localized in the lateral, basal, central, accessory basal and paralaminar amygdala nuclei; basolateral NDI lowering appeared bilaterally. No significant microstructural differences appeared between epilepsy patients with and without current TCS. The central amygdala nuclei, with prominent interactions from surrounding nuclei of that structure, project to cardiovascular regions and respiratory phase switching areas of the parabrachial pons, as well as to the periaqueductal gray. Consequently, they have the potential to modify blood pressure and heart rate, and induce sustained apnea or apneusis. The findings here suggest that lowered NDI, indicative of reduced dendritic density, could reflect an impaired structural organization influencing descending inputs that modulate vital respiratory timing and drive sites and areas critical for blood pressure control

Methods for morphological longitudinal brain modeling through atlasing and registration

Comprendre le développement du cerveau implique d'étudier la relation entre l'âge comme l'une des variables explicatives et des variables expliquées, les observations de cet organe, qui peuvent prendre de nombreuses formes. L'imagerie par résonance magnétique (IRM) permet d'extraire ces observations de manière non invasive et non irradiante. Cette technique puissante permet notamment d'obtenir des informations sur l'activité fonctionnelle du cerveau ou sur ses caractéristiques de diffusivité interne. Pourtant, c'est plutôt sur les aspects purement morphologiques que porte cette thèse. L'approche suivie est celle de l'étude du cerveau en tant qu'objet mathématique, permettant ainsi l'analyse de sa forme et de sa croissance au moyen des transformations géométriques reliant ces objets. Dans la découverte de ces transformations, à travers des structures topologiquement intéressantes, repose le concept de recalage. Cela ouvre la porte à l'analyse statistique des formes et à la création de modèles anatomiques moyens appelés atlas.Understanding brain development involves studying the relationship between age as one of the explanatory variables and explained variables, observations of this organ, which can take many forms. Magnetic Resonance Imaging (MRI) gives the opportunity to extract such observations in a non-invasive and non-irradiating way. This powerful technique allows notably to gain insights about the functional activity of the brain or its internal diffusivity characteristics. Yet, it is rather on the purely morphological aspects that this thesis is focused on. The approach followed the study of the brain as a mathematical object, thus enabling the analysis of its shape and growth by the means of the geometric transformations connecting those objects. In the finding of those transformations, across structures of topological interest, lies the concept of registration. This opens the door to the statistical analysis of shapes and the creation of average anatomical models called atlases

Méthodes pour la modélisation morphologique longitudinale du cerveau via le recalage et la création d'atlas

Understanding brain development involves studying the relationship between age as one of the explanatory variables and explained variables, observations of this organ, which can take many forms. Magnetic Resonance Imaging (MRI) gives the opportunity to extract such observations in a non-invasive and non-irradiating way. This powerful technique allows notably to gain insights about the functional activity of the brain or its internal diffusivity characteristics. Yet, it is rather on the purely morphological aspects that this thesis is focused on. The approach followed the study of the brain as a mathematical object, thus enabling the analysis of its shape and growth by the means of the geometric transformations connecting those objects. In the finding of those transformations, across structures of topological interest, lies the concept of registration. This opens the door to the statistical analysis of shapes and the creation of average anatomical models called atlases.Comprendre le développement du cerveau implique d'étudier la relation entre l'âge comme l'une des variables explicatives et des variables expliquées, les observations de cet organe, qui peuvent prendre de nombreuses formes. L'imagerie par résonance magnétique (IRM) permet d'extraire ces observations de manière non invasive et non irradiante. Cette technique puissante permet notamment d'obtenir des informations sur l'activité fonctionnelle du cerveau ou sur ses caractéristiques de diffusivité interne. Pourtant, c'est plutôt sur les aspects purement morphologiques que porte cette thèse. L'approche suivie est celle de l'étude du cerveau en tant qu'objet mathématique, permettant ainsi l'analyse de sa forme et de sa croissance au moyen des transformations géométriques reliant ces objets. Dans la découverte de ces transformations, à travers des structures topologiquement intéressantes, repose le concept de recalage. Cela ouvre la porte à l'analyse statistique des formes et à la création de modèles anatomiques moyens appelés atlas

Unbiased longitudinal brain atlas creation using robust linear registration and log-Euclidean framework for diffeomorphisms

International audienceWe present a new method to create a diffeomorphic longitudinal (4D) atlas composed of a set of 3D atlases each representing an average model at a given age. This is achieved by generalizing atlasing methods to produce atlases unbiased with respect to the initial reference up to a rigid transformation and ensuring diffeomorphic deformations thanks to the Baker-Campbell-Hausdorff formula and the log-Euclidean framework for diffeomorphisms. Subjects are additionally weighted using an asymmetric function to closely match specified target ages. Creating a longitudinal atlas also implies dealing with subjects with large brain differences that can lead to registration errors. This is overcome by a robust rigid registration based on polar decomposition. We illustrate these techniques for the creation of a 4D pediatric atlas, showing their ability to create a temporally consistent atlas

Similitude anisotrope, une transformation affine contrainte: application à l'analyse du développement cérébral

International audienceThe study of brain development provides insights in the normal trend of brain evolution and enables early detection of abnormalities. We propose a method to quantify brain growth in three arbitrary orthogonal directions of the brain through linear registration. We introduce a 9 degrees of freedom transformation that gives the opportunity to extract scaling factors describing brain growth along those directions by registering a database of subjects in a common basis. We apply this framework to create a longitudinal curve of scaling ratios along fixed orthogonal directions from 0 to 16 years highlighting anisotropic brain development

An iterative centroid approach for diffeomorphic online atlasing

International audienceOnline atlasing, i.e., incrementing an atlas with new images as they are acquired, is key when performing studies on very large, or still being gathered, databases. Regular approaches to atlasing however do not focus on this aspect and impose a complete reconstruction of the atlas when adding images. We propose instead a diffeomorphic online atlasing method that allows gradual updates to an atlas. In this iterative centroid approach, we integrate new subjects in the atlas in an iterative manner, gradually moving the centroid of the images towards its final position. This leads to a computationally cheap approach since it only necessitates one additional registration per new subject added. We validate our approach on several experiments with three main goals: 1-to evaluate atlas image quality of the obtained atlases with sharpness and overlap measures, 2-to assess the deviation in terms of transformations with respect to a conventional atlasing method and 3-to compare its computational time with regular approaches of the literature. We demonstrate that the transformations divergence with respect to a stateof-the-art atlas construction method is small and reaches a plateau, that the two construction methods have the same ability to map subject homologous regions onto a common space and produce images of equivalent quality. The computational time of our approach is also drastically reduced for regular updates. Finally, we also present a direct extension of our method to update spatio-temporal atlases, especially useful for developmental studies

Regional brain development analysis through registration using anisotropic similarity, a constrained affine transformation

International audienceWe propose a novel method to quantify brain growth in 3 arbitrary orthogonal directions of the brain or its sub-regions through linear registration. This is achieved by introducing a 9 degrees of freedom (dof) transformation called anisotropic similarity which is an affine transformation with constrained scaling directions along arbitrarily chosen orthogonal vectors. This gives the opportunity to extract scaling factors describing brain growth along those directions by registering a database of subjects onto a common reference. This information about directional growth brings insights that are not usually available in longitudinal volumetric analysis. The interest of this method is illustrated by studying the anisotropic regional and global brain development of 308 healthy subjects betwen 0 and 19 years old. A gender comparison of those scaling factors is also performed for four age-intervals. We demonstrate through these applications the stability of the method to the chosen reference and its ability to highlight growth differences accros regions and gender

Microstructural dynamics of motor learning and sleep-dependent consolidation: A diffusion imaging study

International audienceMemory consolidation can benefit from post-learning sleep, eventually leading to long-term microstructural brain modifications to accommodate new memory representations. Non-invasive diffusion-weighted magnetic resonance imaging (DWI) allows the observation of (micro)structural brain remodeling after time-limited motor learning. Here, we combine conventional diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) that allows modeling dendritic and axonal complexity in gray matter to investigate with improved specificity the microstructural brain mechanisms underlying time- and sleep-dependent motor memory consolidation dynamics. Sixty-one young healthy adults underwent four DWI sessions, two sequential motor trainings, and a night of total sleep deprivation or regular sleep distributed over five days. We observed rapid-motor-learning-related remodeling in occipitoparietal, temporal, and motor-related subcortical regions, reflecting temporary dynamics in learning-related neuronal brain plasticity processes. Sleep-related consolidation seems not to exert a detectable impact on diffusion parameters, at least on the timescale of a few days

Correction of Susceptibility Distortion in EPI: A Semi-supervised Approach with Deep Learning

Echo planar imaging (EPI) is the most common approach for acquiring diffusion and functional MRI data due to its high temporal resolution. However, this comes at the cost of higher sensitivity to susceptibility-induced B0 field inhomogeneities around air/tissue interfaces. This leads to severe geometric distortions along the phase encoding direction (PED). To correct this distortion, the standard approach involves an analogous acquisition using an opposite PED leading to images with inverted distortions and then non-linear image registration, with a transformation model constrained along the PED, to estimate the voxel-wise shift that undistorts the image pair and generates a distortion-free image. With conventional image registration approaches, this type of processing is computationally intensive. Recent advances in unsupervised deep learning-based approaches to image registration have been proposed to drastically reduce the computational cost of this task. However, they rely on maximizing an intensity-based similarity measure, known to be suboptimal surrogate measures of image alignment. To address this limitation, we propose a semi-supervised deep learning algorithm that directly leverages ground truth spatial transformations during training. Simulated and real data experiments demonstrate improvement to distortion field recovery compared to the unsupervised approach, improvement image similarity compared to supervised approach and precision similar to TOPUP but with much faster processing.SCOPUS: cp.kinfo:eu-repo/semantics/publishe

Multiparametric Analysis of Cerebral Development in Preterm Infants Using Magnetic Resonance Imaging

International audienceObjectives The severity of neurocognitive impairment increases with prematurity. However, its mechanisms remain poorly understood. Our aim was firstly to identify multiparametric magnetic resonance imaging (MRI) markers that differ according to the degree of prematurity, and secondly to evaluate the impact of clinical complications on these markers. Materials and Methods We prospectively enrolled preterm infants who were divided into two groups according to their degree of prematurity: extremely preterm (>28 weeks’ gestational age) and very preterm (28–32 weeks’ gestational age). They underwent a multiparametric brain MRI scan at term-equivalent age including morphological, diffusion tensor and arterial spin labeling (ASL) perfusion sequences. We quantified overall and regional volumes, diffusion parameters, and cerebral blood flow (CBF). We then compared the parameters for the two groups. We also assessed the effects of clinical data and potential MRI morphological abnormalities on those parameters. Results Thirty-four preterm infants were included. Extremely preterm infants ( $n$ = 13) had significantly higher frontal relative volumes ( $p$ = 0.04), frontal GM relative volumes ( $p$ = 0.03), and regional CBF than very preterm infants, but they had lower brainstem and insular relative volumes (respectively $p$ = 0.008 and 0.04). Preterm infants with WM lesions on MRI had significantly lower overall GM CBF (13.3 ± 2 ml/100 g/min versus 17.7 ± 2.5, < ml/100 g/min $p$ = 0.03). Conclusion Magnetic resonance imaging brain scans performed at term-equivalent age in preterm infants provide quantitative imaging parameters that differ with respect to the degree of prematurity, related to brain maturation