Surface Smoothing: A Way Back in Early Brain

Abstract. In this article we propose to investigate the analogy between early cortical folding process and cortical smoothing by mean curvature flow. First, we introduce a one-parameter model that is able to fit a developmental trajectory as represented in a Volume-Area plot and we propose an efficient optimization strategy for parameter estimation. Second, we validate the model on forty cortical surfaces of preterm newborns by comparing global geometrical indices and trajectories of central sulcus along developmental and simulation time.

SPECTRAL CLUSTERING BASED PARCELLATION OF FETAL BRAIN MRI

Many neuroimaging studies are based on the idea that there are distinct brain regions that are functionally or micro-anatomically homogeneous. Obtaining such regions in an au-tomatic way is a challenging task for fetal data due to the lack of strong and consistent anatomical features at the early stages of brain development. In this paper we propose the use of an automatic approach for parcellating fetal cerebral hemi-spheric surfaces into K regions via spectral clustering. Unlike previous methods, our technique has the crucial advantage of only relying on intrinsic geometrical properties of the corti-cal surface and thus being unsupervised. Results on a data-set of fetal brain MRI acquired in utero demonstrated a convinc-ing parcellation reproducibility of the cortical surfaces across fetuses with varying gestational ages and folding magnitude

Morning Plasma Melatonin Differences in Autism: Beyond the Impact of Pineal Gland Volume

While low plasma melatonin, a neuro-hormone synthesized in the pineal gland, has been frequently associated with autism, our understanding of the mechanisms behind it have remained unclear. In this exploratory study, we hypothesized that low melatonin levels in ASD could be linked to a decrease of the pineal gland volume (PGV). PGV estimates with magnetic resonance imaging (MRI) with a voxel-based volumetric measurement method and early morning plasma melatonin levels were evaluated for 215 participants, including 78 individuals with ASD, 90 unaffected relatives, and 47 controls. We first found that both early morning melatonin level and PGV were lower in patients compared to controls. We secondly built a linear model and observed that plasma melatonin was correlated to the group of the participant, but also to the PGV. To further understand the relationship between PGV and melatonin, we generated a normative model of the PGV relationship with melatonin level based on control participant data. We found an effect of PGV on normalized melatonin levels in ASD. Melatonin deficit appeared however more related to the group of the subject. Thus, melatonin variations in ASD could be mainly driven by melatonin pathway dysregulation

HIV Prevalence and Impact on Renutrition in Children Hospitalised for Severe Malnutrition in Niger: An Argument for More Systematic Screening

Background: In developing countries, malnutrition is a contributing factor in over 50 % of child deaths. Mortality rates are higher in underweight children, and HIV-infection is known to increase underweight. Our goals were to evaluate the prevalence of HIV among children hospitalised for severe malnutrition (SM) at the Niamey national hospital (Niger), and to compare renutrition and mortality by HIV-status. Methods: Retrospective study based on all children,5 years hospitalised for SM between January 1 st 2008 and July 1 st 2009. HIV-prevalence was the ratio of HIV+ children on the number of children tested. Duration of renutrition and mortality were described using survival curves. Results: During the study period, 477 children were hospitalised for SM. HIV testing was accepted in 470 (98.5%), of which 40 were HIV+ (HIV prevalence (95 % confidence interval) of 8.6 % (6.2–11.5)). Duration of renutrition was longer in HIV+ than HIV2 children (mean: 22 vs. 15 days; p = 0.003). During renutrition, 8 (20%) and 61 (14%) HIV+ and HIV2 children died, respectively (p = 0.81). Conclusion: Around 9 % of children hospitalised for severe malnutrition were HIV infected, while in Niger HIV prevalence i

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability

SPANOL (SPectral ANalysis of Lobes): A Spectral Clustering Framework for Individual and Group Parcellation of Cortical Surfaces in Lobes

Understanding the link between structure, function and development in the brain is a key topic in neuroimaging that benefits from the tremendous progress of multi-modal MRI and its computational analysis. It implies, inter alia, to be able to parcellate the brain volume or cortical surface into biologically relevant regions. These parcellations may be inferred from existing atlases (e.g., Desikan) or sets of rules, as would do a neuroanatomist for lobes, but also directly driven from the data (e.g., functional or structural connectivity) with minimum a priori. In the present work, we aimed at using the intrinsic geometric information contained in the eigenfunctions of Laplace-Beltrami Operator to obtain parcellations of the cortical surface based only on its description by triangular meshes. We proposed a framework adapted from spectral clustering, which is general in scope and suitable for the co-parcellation of a group of subjects. We applied it to a dataset of 62 adults, optimized it and revealed a striking agreement between parcels produced by this unsupervised clustering and Freesurfer lobes (Desikan atlas), which cannot be explained by chance. Constituting the first reported attempt of spectral-based fully unsupervised segmentation of neuroanatomical regions such as lobes, spectral analysis of lobes (Spanol) could conveniently be fitted into a multimodal pipeline to ease, optimize or speed-up lobar or sub-lobar segmentation. In addition, we showed promising results of Spanol on smoother brains and notably on a dataset of 15 fetuses, with an interest for both the understanding of cortical ontogeny and the applicative field of perinatal computational neuroanatomy

Corrélats anatomo-fonctionnels de l'insuffisance de croissance cérébrale (de l'étude clinique de microcéphalies primitives sévères aux développements méthodologiques en neuroimagerie)

Un adulte porteur de microcéphalie primitive sévère peut avoir le volume cérébral d un enfant sain âgé de 1 an. La constitution de groupes génétiquement homogènes de patients permet d étudier le phénotype spécifique de ces maladies et la façon dont la réduction de volume s installe et modifie l organisation anatomo-fonctionnelle du cerveau. Dans ce travail nous avons : 1) raffiné le spectre phénotypique clinique, radiologique et neuropsychologique associé aux mutations de PQBP1 au sein de la série française des porteurs de maladie de Renpenning ; 2) développé de nouveaux outils d analyse de la gyration corticale afin d explorer la relation allométrique entre volume cérébral et complexité gyrale en population générale et dans 3 groupes de microcéphalies (ASPM, PQBP1 et SAF), permettant une refonte de la notion controversée de simplification gyrale ; 3) initié le développement d un modèle de cinétique de croissance et d une épreuve de mémoire mixte (court et long terme) en IRM fonctionnelle afin d établir de nouveaux endophénotypes en cas de microcéphalie ou de déficience intellectuelle. A l interface entre clinique et neuroimagerie, ce travail multidisciplinaire espère contribuer à une meilleure compréhension des conséquences de l insuffisance de croissance cérébrale au bénéfice de la prise en charge des patients.An adult with severe primary microcephaly may have the same brain volume than a healthy 1-Y/O child. Gathering genetically homogeneous groups of patients enables to study the specific phenotype of each disease and to probe the way volume reduction settles in and modifies both anatomic and functional brain organisation. In this work: 1) we refined the clinical, radiological and neuropsychological spectrum associated with PQBP1 mutations into the French series of Renpenning disease patients ; 2) we developped new tools for the analysis of cortical gyrification to investigate the link between brain volume and gyral complexity in the general population and in 3 groups of microcepahlies (ASPM, PQBP1 and FAS), then updated the disputed concept of simplified gyral pattern ; 3) we started the developpment of a growth kinetics model and of a functional MRI task linking short and long term memories, to estabish new endophenotypes for diseases with either microcephaly or intellectual deficiency. Interfacing clinical and neuroimaging research, this multidisciplinary work hopes to contribute to a further understanding of the consequences of brain growth insufficiency for the sake of patient management.PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Syndrome et troubles du spectre de l’alcoolisation foetale

International audienceLes troubles du spectre de l'alcoolisation fœtale (TSAF) s'étendent le long d'un continuum clinique allant de formes syndromiques ou syndrome d'alcoolisation fœtale (SAF) qui associent dysmorphie faciale caractéristique, déficit de croissance staturopondérale et atteinte du système nerveux central anatomo-fonctionnelle, à des formes où les troubles neurocognitifs sont isolés, sans signes physiques associés. Le diagnostic de TSAF repose donc sur une enquête diagnostique positive et différentielle rigoureuse : il est certain en cas de SAF, probabiliste en cas de TSAF non syndromique. Au cours des TSAF, l'atteinte neurologique fonctionnelle se manifeste par un large panel de déficits cognitifs et adaptatifs s'inscrivant dans le cadre diagnostique des troubles du neurodéveloppement (TND). L'association de troubles (multidys) et la dysfonction exécutive sont la règle, le déficit intellectuel stricto sensu est plus inconstant et souvent léger à limite, des troubles de la régulation affective et des difficultés d'ajustement social sont fréquemment associés. En France, le SAF concerne autour d'une naissance/1000, l'ensemble des TSAF au moins cinq fois plus. Ils ne s'observent pas qu'en cas d'alcoolisme maternel patent. L'effet dose, même s'il est majeur, est fortement modifié par une sensibilité individuelle imprévisible. L'exposition prénatale à l'alcool est une des causes les plus fréquentes et, paradoxalement, les plus négligées de TND. En l'absence de seuil d'innocuité généralisable, il reste recommandé de s'abstenir de consommer de l'alcool pendant la grossesse. Il faut donc rechercher un facteur d'exposition toxique devant tout TND, isolé ou associé à des signes physiques. L'objectif est de ne pas passer à côté d'une cause très fréquente, de rationaliser l'enquête étiologique, et surtout de faire bénéficier l'enfant et sa famille d'un diagnostic précoce, permettant souvent de mettre un terme aux interprétations inadaptées, d'orienter la prise en charge, de limiter les troubles secondaires et de prévenir un risque majeur de récidive pour les enfants à venir

Perturbation of Fiedler vector: interest for graph measures and shape analysis

In this paper we investigate some properties of the Fiedler vector, the so-called first non-trivial eigenvector of the Laplacian matrix of a graph. There are important results about the Fiedler vector to identify spectral cuts in graphs but far less is known about its extreme values and points. We propose a few results and conjectures in this direction. We also bring two concrete contributions, i) by defining a new measure for graphs that can be interpreted in terms of extremality (inverse of centrality), ii) by applying a small perturbation to the Fiedler vector of cerebral shapes such as the corpus callosum to robustify their parameterization

Spectral-based thickness profiling of the corpus callosum enhances anomaly detection in fetal alcohol spectrum disorders

IntroductionFetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic forms (NS-FASD). The neuroanatomical consequences of prenatal alcohol exposure are mainly the reduction in brain size, but also focal abnormalities such as those of the corpus callosum (CC). We previously showed a narrowing of the CC for brain size, using manual measurement and its usefulness to improve diagnostic certainty. Our aim was to automate these measurements of the CC and identify more recurrent abnormalities in FAS subjects, independently of brain size reduction.MethodsWe developed a fast, automated, and normalization-free method based on spectral analysis to generate thicknesses of the CC continuously and at singular points (genu, body, isthmus, and splenium), and its length (LCC). We applied it on midsagittal section of the CC extracted from T1-anatomical brain MRI of 89 subjects with FASD (52 FAS, 37 NS-FASD) and 126 with typically development (6–20 y-o). After adjusting for batch effect, we compared the mean profiles and thicknesses of the singular points across the 3 groups. For each parameter, we established variations with age (growth charts) and brain size in the control group (scaling charts), then identified participants with abnormal measurements (<10th percentile).ResultsWe confirmed the slimming of the posterior half of the CC in both FASD groups, and of the genu section in the FAS group, compared to the control group. We found a significant group effect for the LCC, genu, median body, isthmus, and splenium thicknesses (p < 0.05). We described a body hump whose morphology did not differ between groups. According to the growth charts, there was an excess of FASD subjects with abnormal LCC and isthmus, and of FAS subjects with abnormal genu and splenium. According to the scaling charts, this excess remained only for LCC, isthmus and splenium, undersized for brain size.ConclusionWe characterized size-independent anomalies of the posterior part of the CC in FASD, with an automated method, confirming and extending our previous study. Our new tool brings the use of a neuroanatomical criterion including CC damage closer to clinical practice. Our results suggest that an FAS signature identified in NS-FASD, could improve diagnosis specificity