Détection automatique de Mitoses dans des images Histopathologiques haut-contenu, couleur multispectrales : application à la gradation du cancer du sein en pathologie numérique

Digital pathology represents one of the major and challenging evolutions in modernmedicine. Pathological exams constitute not only the gold standard in most of medicalprotocols, but also play a critical and legal role in the diagnosis process. Diagnosing adisease after manually analyzing numerous biopsy slides represents a labor-intensive workfor pathologists. Thanks to the recent advances in digital histopathology, the recognitionof histological tissue patterns in a high-content Whole Slide Image (WSI) has the potentialto provide valuable assistance to the pathologist in his daily practice. Histopathologicalclassification and grading of biopsy samples provide valuable prognostic information thatcould be used for diagnosis and treatment support. Nottingham grading system is thestandard for breast cancer grading. It combines three criteria, namely tubule formation(also referenced as glandular architecture), nuclear atypia and mitosis count. Manualdetection and counting of mitosis is tedious and subject to considerable inter- and intrareadervariations. The main goal of this dissertation is the development of a framework ableto provide detection of mitosis on different types of scanners and multispectral microscope.The main contributions of this work are eight fold. First, we present a comprehensivereview on state-of-the-art methodologies in nuclei detection, segmentation and classificationrestricted to two widely available types of image modalities: H&E (HematoxylinEosin) and IHC (Immunohistochemical). Second, we analyse the statistical and morphologicalinformation concerning mitotic cells on different color channels of various colormodels that improve the mitosis detection in color datasets (Aperio and Hamamatsu scanners).Third, we study oversampling methods to increase the number of instances of theminority class (mitosis) by interpolating between several minority class examples that lietogether, which make classification more robust. Fourth, we propose three different methodsfor spectral bands selection including relative spectral absorption of different tissuecomponents, spectral absorption of H&E stains and mRMR (minimum Redundancy MaximumRelevance) technique. Fifth, we compute multispectral spatial features containingpixel, texture and morphological information on selected spectral bands, which leveragediscriminant information for mitosis classification on multispectral dataset. Sixth, we performa comprehensive study on region and patch based features for mitosis classification.Seven, we perform an extensive investigation of classifiers and inference of the best one formitosis classification. Eight, we propose an efficient and generic strategy to explore largeimages like WSI by combining computational geometry tools with a local signal measureof relevance in a dynamic sampling framework.The evaluation of these frameworks is done in MICO (COgnitive MIcroscopy, ANRTecSan project) platform prototyping initiative. We thus tested our proposed frameworks on MITOS international contest dataset initiated by this project. For the color framework,we manage to rank second during the contest. Furthermore, our multispectral frameworkoutperforms significantly the top methods presented during the contest. Finally, ourframeworks allow us reaching the same level of accuracy in mitosis detection on brightlightas multispectral datasets, a promising result on the way to clinical evaluation and routine.La gradation de lames de biopsie fournit des informations pronostiques essentielles pour le diagnostic et le traitement. La détection et le comptage manuel des mitoses est un travail fastidieux, sujet à des variations inter-et intra- observateur considérables. L'objectif principal de cette thèse de doctorat est le développement d'un système capable de fournir une détection des mitoses sur des images provenant de différents types de scanners rapides automatiques, ainsi que d'un microscope multispectral. L'évaluation des différents systèmes proposés est effectuée dans le cadre du projet MICO (MIcroscopie COgnitive, projet ANR TecSan piloté par notre équipe). Dans ce contexte, les systèmes proposés ont été testés sur les données du benchmark MITOS. En ce qui concerne les images couleur, notre système s'est ainsi classé en deuxième position de ce concours international, selon la valeur du critère F-mesure. Par ailleurs, notre système de détection de mitoses sur images multispectrales surpasse largement les meilleurs résultats obtenus durant le concours