Détection automatique de glomérules en pathologie digitale

Dans cet article, nous proposons une méthodologie de détection de glomérules au sein d’images de biopsies rénales. Elle combine des techniques de traitement d’images et d’apprentissage supervisé. Nous évaluons l’approche sur des images présentant plusieurs sources de variations et montrons que les comptages automatiques sont très bien corrélés avec les comptages des expert

An approach for detection of glomeruli in multisite digital pathology

peer reviewedWe present a novel bioimage informatics workflow that combines Icy and Cytomine software and their algorithms to enable large-scale analysis of digital slides from multiple sites. In particular, we apply this workflow on renal biopsies and evaluate empirically our approach for the automatic detection of glomeruli in hundreds of tissue sections

Morphological operations on polygons using straight skeletons for digital pathology

International audienceIn the context Digital Pathology, this work presents an efficient implementation of vector-based mathematical morphological operators applied to simple polygons. We achieve this by performing wavefront propagation and computing polygon straight skeletons. We present several applications of this method on histo-pathological images

The Intracellular Bacteria Chlamydia Hijack Peroxisomes and Utilize Their Enzymatic Capacity to Produce Bacteria-Specific Phospholipids

International audienceChlamydia trachomatis is an obligate intracellular pathogen responsible for loss of eyesight through trachoma and for millions of cases annually of sexually transmitted diseases. The bacteria develop within a membrane-bounded inclusion. They lack enzymes for several biosynthetic pathways, including those to make some phospholipids, and exploit their host to compensate. Three-dimensional fluorescence microscopy demonstrates that small organelles of the host, peroxisomes, are translocated into the Chlamydia inclusion and are found adjacent to the bacteria. In cells deficient for peroxisome biogenesis the bacteria are able to multiply and give rise to infectious progeny, demonstrating that peroxisomes are not essential for bacterial development in vitro. Mass spectrometry-based lipidomics reveal the presence in C. trachomatis of plasmalogens, ether phospholipids whose synthesis begins in peroxisomes and have never been described in aerobic bacteria before. Some of the bacterial plasmalogens are novel structures containing bacteria-specific odd-chain fatty acids; they are not made in uninfected cells nor in peroxisome-deficient cells. Their biosynthesis is thus accomplished by the metabolic collaboration of peroxisomes and bacteria

Spatial Analysis For Histopathology: A Statistical Approach

International audienceA pattern analysis approach is proposed to model spatial interaction between the immune cells and the tumor islets within the tumor microenvironment. Embedded in a statistical null hypothesis paradigm, the proposed solution provides a novel mechanism to extract quantitative, system-level snapshot of the tumor microenvironment during immunotherapy. Experimental results on synthetic and real histopathological data suggest the potential of our technique in mining robust informatics from the spatial distribution of immune cells at different time-points during cancer treatment, and this could be potentially adopted in large-scale experimental studies in the future to objectively monitor disease progression and the patient's response to immune therapy

Smart Learning of Click and Refine for Nuclei Segmentation on Histology Images

International audienceDeep learning has proven to be a very efficient tool to help pathologists analyze Whole Slide Images (WSI) toward automated classification or segmentation of detailed structures such as nuclei, glands or glomeruli. These objects are particularly relevant for disease diagnosis and staging. Many deep learning methods have shown impressive performance but are still imperfect, while manual segmentation has poor inter-rater agreement. In this paper, we propose a patch-level automated correction of a given baseline initial segmentation, based on deep-learning of segmentation errors and downstream local refinements. Results on the MoNuSeg and PanNuke test datasets show significant improvement of nuclei segmentation quality

Pak1 Phosphorylation Enhances Cortactin-N-WASP Interaction in Clathrin-Caveolin-Independent Endocytosis.

International audienceGrowing evidence indicates that kinases are central to the regulation of endocytic pathways. Previously, we identified p21-activated kinase 1 (Pak1) as the first specific regulator of clathrin- and caveolae-independent endocytosis used by the interleukin 2 receptor subunit (IL-2R). Here, we address the mechanism by which Pak1 regulates IL-2Rbeta endocytosis. First, we show that Pak1 phosphorylates an activator of actin polymerization, cortactin, on its serine residues 405 and 418. Consistently, we observe a specific inhibition of IL-2Rbeta endocytosis when cells overexpress a cortactin, wherein these serine residues have been mutated. In addition, we show that the actin polymerization enhancer, neuronal Wiskott-Aldrich syndrome protein (N-WASP), is involved in IL-2Rbeta endocytosis. Strikingly, we find that Pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with N-WASP. Thus, Pak1, by controlling the interaction between cortactin and N-WASP, could regulate the polymerization of actin during clathrin-independent endocytosis

The Lifecycle of a Neural Network in the Wild: A Multiple Instance Learning Study on Cancer Detection from Breast Biopsies Imaged with Novel Technique

International audienceIn the context of tissue examination for breast cancer assessment, we propose a label-free imaging based on Optical Coherence Tomography (OCT) signal combined with a multiple instance learning (MIL) model to respond to a critical need for fast at point-of-care diagnosis: biopsy or surgery time. This new imaging, Dynamic Cell Imaging (DCI), is the time-resolved variant of Full-Field OCT (FFOCT) and offers an intra-cellular resolution of about 1 micron, together with optical sectioning and an improved cell contrast. In order to tackle the challenges of limited data and annotations, while remaining in the scope of interpretability, we design an instance-level MIL model with a focus on adapted data sampling. The interest of this method is that it incorporates taskspecific feature learning and also produces instance predictions. For a dataset of 150 core-needle biopsies, we achieve a considerable improvement of more than 20 percentage points in specificity and about 10 in accuracy by leveraging intradomain (as compared to extra-domain) pre-training

Essential role of immobilized chemokine CXCL12 in the regulation of the humoral immune response.

International audienceChemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptor-binding domain is distinct and does not overlap with the immobilization domains. Although CXCL12 is known to be essential for the germinal center (GC) response, the role of its immobilization in biological functions has never been addressed. In this work, we investigated the unexplored paradigm of CXCL12 immobilization during the germinal center reaction, a fundamental process where cellular traffic is crucial for the quality of humoral immune responses. We show that the structure of murine germinal centers and the localization of GC B cells are impaired when CXCL12 is unable to bind to cellular or extracellular surfaces. In such mice, B cells carry fewer somatic mutations in Ig genes and are impaired in affinity maturation. Therefore, immobilization of CXCL12 is necessary for proper trafficking of B cells during GC reaction and for optimal humoral immune responses

Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb.

International audienceIn the olfactory bulb (OB), new neurons are added throughout life, forming an integral part of the functioning circuit. Yet only some of them survive more than a month. To determine whether this turnover depends on olfactory learning, we examined the survival of adult newborn cells labeled with the cell division marker BrdU, administered before learning in an olfactory discrimination task. We report that discrimination learning increases the number of newborn neurons in the adult OB by prolonging their survival. Simple exposure to the pair of olfactory cues did not alter neurogenesis, indicating that the mere activation of sensory inputs during the learning task was insufficient to alter neurogenesis. The increase in cell survival after learning was not uniformly distributed throughout angular sectors of coronal sections of the OB. Monitoring odor activation maps using patterns of Zif268 immediate early gene expression revealed that survival was greater in regions more activated by the non-reinforced odorant. We conclude that sensory activation in a learning context not only controls the total number of newborn neurons in the adult OB, but also refines their precise location. Shaping the distribution of newborn neurons by influencing their survival could optimize the olfactory information processing required for odor discrimination