Cross-subject variability of the optic radiation anatomy in a cohort of 1065 healthy subjects.

INTRODUCTION: Optic radiations are tracts of particular interest for neurosurgery, especially for temporal lobe resection, because their lesion is responsible for visual field defects. However, histological and MRI studies found a high inter-subject variability of the optic radiation anatomy, especially for their most rostral extent inside the Meyer's temporal loop. We aimed to better assess inter-subject anatomical variability of the optic radiations, in order to help to reduce the risk of postoperative visual field deficiencies. METHODS: Using an advanced analysis pipeline relying on a whole-brain probabilistic tractography and fiber clustering, we processed the diffusion MRI data of the 1065 subjects of the HCP cohort. After registration in a common space, a cross-subject clustering on the whole cohort was performed to reconstruct the reference optic radiation bundle, from which all optic radiations were segmented on an individual scale. RESULTS: We found a median distance between the rostral tip of the temporal pole and the rostral tip of the optic radiation of 29.2 mm (standard deviation: 2.1 mm) for the right side and 28.8 mm (standard deviation: 2.3 mm) for the left side. The difference between both hemispheres was statistically significant (p = 1.10-8). CONCLUSION: We demonstrated inter-individual variability of the anatomy of the optic radiations on a large-scale study, especially their rostral extension. In order to better guide neurosurgical procedures, we built a MNI-based reference atlas of the optic radiations that can be used for fast optic radiation reconstruction from any individual diffusion MRI tractography.

Enhanced Automatic Segmentation for Superficial White Matter Fiber Bundles for Probabilistic Tractography Datasets.

This paper presents an enhanced algorithm for automatic segmentation of superficial white matter (SWM) bundles from probabilistic dMRI tractography datasets, based on a multi-subject bundle atlas. Previous segmentation methods use the maximum Euclidean distance between corresponding points of the subject fibers and the atlas centroids. However, this scheme might include noisy fibers. Here, we propose a three step approach to discard noisy fibers improving the identification of fibers. The first step applies a fiber clustering and the segmentation is performed between the centroids of the clusters and the atlas centroids. This step removes outliers and enables a better identification of fibers with similar shapes. The second step applies a fiber filter based on two different fiber similarities. One is the Symmetrized Segment-Path Distance (SSPD) over 2D ISOMAP and the other is an adapted version of SSPD for 3D space. The last step eliminates noisy fibers by removing those that connect regions that are far from the main atlas bundle connections. We perform an experimental evaluation using ten subjects of the Human Connectome (HCP) database. The evaluation only considers the bundles connecting precentral and postcentral gyri, with a total of seven bundles per hemisphere. For comparison, the bundles of the ten subjects were manually segmented. Bundles segmented with our method were evaluated in terms of similarity to manually segmented bundles and the final number of fibers. The results show that our approach obtains bundles with a higher similarity score than the state-of-the-art method and maintains a similar number of fibers.Clinical relevance-Many brain pathologies or disorders can occur in specific regions of the SWM automatic segmentation of reliable SWM bundles would help applications to clinical research.

Extracellular Pax6 Regulates Tangential Cajal-Retzius Cell Migration in the Developing Mouse Neocortex.

The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.

The effect of the number of fibers in tractography reconstruction of white matter bundles.

The study of white matter (WM) through diffusion Magnetic Resonance Imaging (dMRI) is crucial to obtain a better understanding of human brain connections and functions, at a macroscopic level. A large number of works have focused on long range brain connections, while recently, several studies have also analyzed superficial WM connectivity. In recent years, with the massive use of HCP database, and its processing with known softwares like DSI Studio and MRtrix, it is necessary to evaluate the influence of tractography parameters on the reconstruction of fiber bundles and further analyses. We study the effect of the number of fibers, for whole brain tractography, on the reconstruction of deep and superficial WM bundles based on their segmentation using multi-subject bundle atlases. For DSI Studio (deterministic algorithm), a value of 1M fibers could reconstruct most of deep white matter (DWM) bundles, while a value of 1.5M was required for superficial white matter (SWM) bundles. In the case of MRtrix (probabilistic algorithm), a value of 3M fibers was found to be suitable for the study of both kinds of fibers. Furthermore, we found the tracking of SWM bundles to be more sensitive to several parameters than DWM, for DSI Studio.

Mapping the asynchrony of cortical maturation in the infant brain: A MRI multi-parametric clustering approach.

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.

A framework based on sulcal constraints to align preterm, infant and adult human brain images acquired in vivo and post mortem.

Robust spatial alignment of post mortem data and in vivo MRI acquisitions from different ages, especially from the early developmental stages, into standard spaces is still a bottleneck hampering easy comparison with the mainstream neuroimaging results. In this paper, we test a landmark-based spatial normalization strategy as a framework for the seamless integration of any macroscopic dataset in the context of the Human Brain Project (HBP). This strategy stems from an approach called DISCO embedding sulcal constraints in a registration framework used to initialize DARTEL, the widely used spatial normalization approach proposed in the SPM software. We show that this strategy is efficient with a heterogeneous dataset including challenging data as preterm newborns, infants, post mortem histological data and a synthetic atlas computed from averaging the ICBM database, as well as more commonly studied data acquired in vivo in adults. We then describe some perspectives for a research program aiming at improving folding pattern matching for atlas inference in the context of the future HBP's portal.

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease.

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.

Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates.

Dissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways. For the proof-of-concept this approach was used in the NHP brain to characterize the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS action mechanism in Parkinson's disease (PD). Rabies-G-pseudotyped and Rabies-G-VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely transported to the layer of the motor cortex projecting to STN. A precise anatomical mapping of this pathway was then performed using histology-guided high angular resolution MRI tractography guiding accurately cortical photostimulation of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical origins modified the spikes distribution for photosensitive STN neurons firing rate in non-equivalent ways. Optogenetic tractography might help design preclinical neuromodulation studies in NHP models of neuropsychiatric disease choosing the most appropriate target for the tested hypothesis.

Diffusion magnetic resonance imaging in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is frequent in the elderly, and accounts for a wide spectrum of clinical and radiological manifestations. This report summarizes the most important findings obtained using diffusion MRI (DWI) in SVD. With DWI and apparent diffusion coefficient (ADC) maps, recent ischemic lesions can easily be detected after acute stroke in SVD, while even multiple simultaneous lesions may be observed. Microstructural changes are frequent in SVD, with increases in diffusivity and decreases in anisotropy being the most reliable findings observed, mainly in white matter. These tissue changes are associated with clinical severity and especially executive dysfunction. They can also precede the usual MRI markers of SVD, such as white matter hyperintensities, microbleeds and lacunes. Thus, DWI may reveal surrogate markers of SVD progression and offer a better understanding of their underlying mechanisms.

White matter changes in microstructure associated with a maladaptive response to stress in rats.

In today's society, every individual is subjected to stressful stimuli with different intensities and duration. This exposure can be a key trigger in several mental illnesses greatly affecting one's quality of life. Yet not all subjects respond equally to the same stimulus and some are able to better adapt to them delaying the onset of its negative consequences. The neural specificities of this adaptation can be essential to understand the true dynamics of stress as well as to design new approaches to reduce its consequences. In the current work, we employed ex vivo high field diffusion magnetic resonance imaging (MRI) to uncover the differences in white matter properties in the entire brain between Fisher 344 (F344) and Sprague-Dawley (SD) rats, known to present different responses to stress, and to examine the effects of a 2-week repeated inescapable stress paradigm. We applied a tract-based spatial statistics (TBSS) analysis approach to a total of 25 animals. After exposure to stress, SD rats were found to have lower values of corticosterone when compared with F344 rats. Overall, stress was found to lead to an overall increase in fractional anisotropy (FA), on top of a reduction in mean and radial diffusivity (MD and RD) in several white matter bundles of the brain. No effect of strain on the white matter diffusion properties was observed. The strain-by-stress interaction revealed an effect on SD rats in MD, RD and axial diffusivity (AD), with lower diffusion metric levels on stressed animals. These effects were localized on the left side of the brain on the external capsule, corpus callosum, deep cerebral white matter, anterior commissure, endopiriform nucleus, dorsal hippocampus and amygdala fibers. The results possibly reveal an adaptation of the SD strain to the stressful stimuli through synaptic and structural plasticity processes, possibly reflecting learning processes.

Spatial normalization of brain images and beyond.

The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images.

Similar white matter but opposite grey matter changes in schizophrenia and high-functioning autism.

OBJECTIVE: High-functioning autism (HFA) and schizophrenia (SZ) are two of the main neurodevelopmental disorders, sharing several clinical dimensions and risk factors. Their exact relationship is poorly understood, and few studies have directly compared both disorders. Our aim was thus to directly compare neuroanatomy of HFA and SZ using a multimodal MRI design. METHODS: We scanned 79 male adult subjects with 3T MRI (23 with HFA, 24 with SZ and 32 healthy controls, with similar non-verbal IQ). We compared them using both diffusion-based whole-brain tractography and T1 voxel-based morphometry. RESULTS: HFA and SZ groups exhibited similar white matter alterations in the left fronto-occipital inferior fasciculus with a decrease in generalized fractional anisotropy compared with controls. In grey matter, the HFA group demonstrated bilateral prefrontal and anterior cingulate increases in contrast with prefrontal and left temporal reductions in SZ. CONCLUSION: HFA and SZ may share common white matter deficits in long-range connections involved in social functions, but opposite grey matter abnormalities in frontal regions that subserve complex cognitive functions. Our results are consistent with the fronto-occipital underconnectivity theory of HFA and the altered connectivity hypothesis of SZ and suggest the existence of both associated and diametrical liabilities to these two conditions.

[Predictive factors of 2-month postpartum anal incontinence among patients with an obstetrical anal sphincter injury]. / Facteurs pronostiques d'incontinence anale à 2 mois du post-partum après survenue d'un périnée complet.

OBJECTIVES: To determine prevalence of short-term postpartum anal incontinence after obstetrical anal sphincter injury and prognostic factors. MATERIALS AND METHODS: Retrospective study including every patient with an obstetrical anal sphincter injury between January 2006 and December 2012 in one tertiary maternity unit. Patients were interviewed and examined at 2-month postpartum. Anal incontinence was defined by the presence of at least one of the following symptoms: flatus incontinence, faecal incontinence and faecal urgency. RESULTS: Among 17,110 patients who delivered vaginally during period study, 134 (0.8%) presented an anal sphincter injury. Postpartum obstetrical data were available for 110 of them. Among those patients, 50 women (45.5%) had at least one symptom of anal incontinence at 2-month postpartum and 8 (7.3%) had faecal incontinence. Only maternal age and second stage duration were significantly associated with anal incontinence after obstetrical anal sphincter injury. The degree of sphincter damage at delivery (IIIa, b, c, IV) was not associated with the risk of anal incontinence at 2-month postpartum. CONCLUSION: Maternal age and second stage duration were the only risk factor for anal incontinence after obstetrical anal sphincter injury in this study. High prevalence of anal incontinence at 2-month postpartum of obstetrical anal sphincter injury is observed no matter what is the degree of anal sphincter damage. Our results highlight the importance to diagnose all obstetrical anal sphincter injuries whatever the degree of damage.

Endometrial cancer in elderly women: Which disease, which surgical management? A systematic review of the literature.

OBJECTIVE: Endometrial cancer primarily affects elderly women. The aim of the present literature review is to define the population of elderly women with this disease and to define the characteristics of this cancer in elderly people as well as its surgical treatment. MATERIALS AND METHODS: A systematic review of the English-language literature of the last 20 years indexed in the PubMed database. RESULTS: Endometrial cancer is more aggressive in elderly women. However, surgical staging performed in elderly patients is often not concomitant with the disease's aggressiveness in this group. Mini-invasive surgery is performed less often, for no obvious reason. Of note, oncogeriatric evaluation was not usually ruled out to determine the most appropriate surgical modality. CONCLUSION: Studies are needed to evaluate surgical management of endometrial cancer in elderly women, notably with the aid of oncogeriatric scores to predict surgical morbidity.

Creation of a whole brain short association bundle atlas using a hybrid approach.

The Human brain connection map is far from being complete. In particular the study of the superficial white matter (SWM) is an unachieved task. Its description is essential for the understanding of human brain function and the study of pathogenesis triggered by abnormal connectivity. In this work we expanded a previously developed method for the automatic creation of a whole brain SWM bundle atlas. The method is based on a hybrid approach. First a cortical parcellation is used to extract fibers connecting two regions. Then an intra-and inter-subject hierarchical clustering are applied to find well-defined SWM bundles reproducible across subjects. In addition to the fronto-parietal and insula regions of the left hemisphere, the analysis was extended to the temporal and occipital lobes, including all their internal regions, for both hemispheres. Validation steps are performed in order to test the robustness of the method and the reproducibility of the obtained bundles. First the method was applied to two independent groups of subjects, in order to discard bundles without match across the two independent atlases. Then, the resulting intersection atlas was projected on a third independent group of subjects in order to filter out bundles without reproducible and reliable projection. The final multi-subject U-fiber atlas is composed of 100 bundles in total, 50 per hemisphere, from which 35 are common to both hemispheres. The atlas can be used in clinical studies for segmentation of the SWM bundles in new subjects, and measure DW values or complement functional data.

Short association bundle atlas based on inter-subject clustering from HARDI data.

This paper is focused on the study of short brain association fibers. We present an automatic method to identify short bundles of the superficial white matter based on inter-subject hierarchical clustering. Our method finds clusters of similar fibers, belonging to the different subjects, according to a distance measure between fibers. First, the algorithm obtains representative bundles and subsequently we perform an automatic labeling based on the anatomy, of the most stable connections. The analysis was applied to two independent groups of 37 subjects. Results between the two groups were compared, in order to keep reproducible connections for the atlas creation. The method was applied using linear and non-linear registration, where the non-linear registration showed significantly better results. A final atlas with 35 bundles in the left hemisphere and 27 in the right hemisphere from the whole brain was obtained. Finally results were validated using the atlas to segment 26 new subjects from another HARDI database.

Cerebellar volume in schizophrenia and bipolar I disorder with and without psychotic features.

OBJECTIVE: There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder. METHOD: One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates. RESULTS: Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. CONCLUSION: Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.

Organic carbon, and major and trace element dynamic and fate in a large river subjected to poorly-regulated urban and industrial pressures (Sebou River, Morocco).

An annual-basis study of the impacts of the anthropogenic inputs from Fez urban area on the water geochemistry of the Sebou and Fez Rivers was conducted mostly focusing on base flow conditions, in addition to the sampling of industrial wastewater characteristic of the various pressures in the studied environment. The measured trace metals dissolved/particulate partitioning was compared to the ones predicted using the WHAM-VII chemical speciation code. The Sebou River, upstream from Fez city, showed a weakly polluted status. Contrarily, high levels of major ions, organic carbon and trace metals were encountered in the Fez River and the Sebou River downstream the Fez inputs, due to the discharge of urban and industrial untreated and hugely polluted wastewaters. Trace metals were especially enriched in particles with levels even exceeding those recorded in surface sediments. The first group of elements (Al, Fe, Mn, Ti, U and V) showed strong inter-relationships, impoverishment in Fez particles/sediments and stable partition coefficient (Kd), linked to their lithogenic origin from Sebou watershed erosion. Conversely, most of the studied trace metals/metalloids, originated from anthropogenic sources, underwent significant changes of Kd and behaved non-conservatively in the Sebou/Fez water mixing. Dissolved/particulate partitioning was correctly assessed by WHAM-VII modeling for Cu, Pb and Zn, depicting significant differences in chemical speciation in the Fez River when compared to that in the Sebou River. The results of this study demonstrated that a lack of compliance in environmental regulations certainly explained this poor status.

Multi-parametric evaluation of the white matter maturation.

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.