The recent challenge in high angular resolution diffusion imaging (HARDI) is to find a tractography process that provides information about the neural architecture within the white matter of the brain in a clinically feasible measurement time. The great success of the HARDI technique comes from its capability to overcome the problem of crossing fiber detection. However, it requires a large number of diffusion-weighted (DW) images which is problematic for clinical time and hardware. The main contribution of this paper is to develop a full tractography framework that gives an accurate estimate of the crossing fiber problem with the aim of reducing data acquisition time. We explore the interpolation in the gradient direction domain as a method to estimate the HARDI signal from a reduced set of DW images. The experimentation was performed in a first time on simulated data for a quantitative evaluation using the Tractometer system. We used, also, in vivo human brain data to demonstrate the potential of our pipeline. Results on both simulated and real data illustrate the effectiveness of our approach to perform the brain connectivity. Overall, we have shown that the proposed approach achieves competitive results to other tractography methods according to Tractometer connectivity metrics. Graphical Abstract.

While the main neural networks are in place at term birth, intense changes in cortical microstructure occur during early infancy with the development of dendritic arborization, synaptogenesis and fiber myelination. These maturational processes are thought to relate to behavioral acquisitions and the development of cognitive abilities. Nevertheless, in vivo investigations of such relationships are still lacking in healthy infants. To bridge this gap, we aimed to study the cortical maturation using non-invasive Magnetic Resonance Imaging, over a largely unexplored period (1-5 post-natal months). In a first univariate step, we focused on different quantitative parameters: longitudinal relaxation time (T1), transverse relaxation time (T2), and axial diffusivity from diffusion tensor imaging (λ//) These individual maps, acquired with echo-planar imaging to limit the acquisition time, showed spatial distortions that were first corrected to reliably match the thin cortical ribbon identified on high-resolution T2-weighted images. Averaged maps were also computed over the infants group to summarize the parameter characteristics during early infancy. In a second step, we considered a multi-parametric approach that leverages parameters complementarity, avoids reliance on pre-defined regions of interest, and does not require spatial constraints. Our clustering strategy allowed us to group cortical voxels over all infants in 5 clusters with distinct microstructural T1 and λ// properties The cluster maps over individual cortical surfaces and over the group were in sound agreement with benchmark post mortem studies of sub-cortical white matter myelination, showing a progressive maturation of 1) primary sensori-motor areas, 2) adjacent unimodal associative cortices, and 3) higher-order associative regions. This study thus opens a consistent approach to study cortical maturation in vivo.

Already during the last trimester of gestation, functional responses are recorded in foetuses and preterm newborns, attesting an already complex cerebral architecture. Then throughout childhood, anatomical connections are further refined but at different rates and over asynchronous periods across functional networks. Concurrently, infants gradually achieve new psychomotor and cognitive skills. Only the recent use of non-invasive techniques such as magnetic resonance imaging (MRI) and magneto- and electroencephalography (M/EEG) has opened the possibility to understand the relationships between brain maturation and skills development in vivo. In this review, we describe how these techniques have been applied to study the white matter maturation. At the structural level, the early architecture and myelination of bundles have been assessed with diffusion and relaxometry MRI, recently integrated in multi-compartment models and multi-parametric approaches. Nevertheless, technical limitations prevent us to map major developmental mechanisms such as fibers growth and pruning, and the progressive maturation at the bundle scale in case of mixing trajectories. At the functional level, M/EEG have been used to record different visual, somatosensory and auditory evoked responses. Because the conduction velocity of neural impulses increases with the myelination of connections, major changes in the components latency are observed throughout development. But so far, only a few studies have related structural and functional markers of white matter myelination. Such multi-modal approaches will be a major challenge in future research, not only to understand normal development, but also to characterize early mechanisms of pathologies and the influence of fetal and perinatal interventions on later outcome.

Isolated corpus callosum dysgenesis (CCD) is a congenital malformation which occurs during early development of the brain. In this study, we aimed to identify and describe its consequences beyond the lack of callosal fibres, on the morphology, microstructure and asymmetries of the main white matter bundles with diffusion imaging and fibre tractography. Seven children aged between 9 and 13 years old and seven age- and gender-matched control children were studied. First, we focused on bundles within the mesial region of the cerebral hemispheres: the corpus callosum, Probst bundles and cingulum which were selected using a conventional region-based approach. We demonstrated that the Probst bundles have a wider connectivity than the previously described rostrocaudal direction, and a microstructure rather distinct from the cingulum but relatively close to callosal remnant fibres. A sigmoid bundle was found in two partial ageneses. Second, the corticospinal tract, thalamic radiations and association bundles were extracted automatically via an atlas of adult white matter bundles to overcome bias resulting from a priori knowledge of the bundles\' anatomical morphology and trajectory. Despite the lack of callosal fibres and the colpocephaly observed in CCD, all major white matter bundles were identified with a relatively normal morphology, and preserved microstructure (i.e. fractional anisotropy, mean diffusivity) and asymmetries. Consequently the bundles\' organisation seems well conserved in brains with CCD. These results await further investigations with functional imaging before apprehending the cognition variability in children with isolated dysgenesis.

In vivo evaluation of the brain white matter maturation is still a challenging task with no existing gold standards. In this article we propose an original approach to evaluate the early maturation of the white matter bundles, which is based on comparison of infant and adult groups using the Mahalanobis distance computed from four complementary MRI parameters: quantitative qT1 and qT2 relaxation times, longitudinal λ║ and transverse λ⊥ diffusivities from diffusion tensor imaging. Such multi-parametric approach is expected to better describe maturational asynchrony than conventional univariate approaches because it takes into account complementary dependencies of the parameters on different maturational processes, notably the decrease in water content and the myelination. Our approach was tested on 17 healthy infants (aged 3- to 21-week old) for 18 different bundles. It finely confirmed maturational asynchrony across the bundles: the spino-thalamic tract, the optic radiations, the cortico-spinal tract and the fornix have the most advanced maturation, while the superior longitudinal and arcuate fasciculi, the anterior limb of the internal capsule and the external capsule have the most delayed maturation. Furthermore, this approach was more reliable than univariate approaches as it revealed more maturational relationships between the bundles and did not violate a priori assumptions on the temporal order of the bundle maturation. Mahalanobis distances decreased exponentially with age in all bundles, with the only difference between them explained by different onsets of maturation. Estimation of these relative delays confirmed that the most dramatic changes occur during the first post-natal year.