Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Deep Learning Based Medical Image Analysis with Limited Data

Deep Learning Methods have shown its great effort in the area of Computer Vision. However, when solving the problems of medical imaging, deep learning’s power is confined by limited data available. We present a series of novel methodologies for solving medical imaging analysis problems with limited Computed tomography (CT) scans available. Our method, based on deep learning, with different strategies, including using Generative Adversar- ial Networks, two-stage training, infusing the expert knowledge, voting based or converting to other space, solves the data set limitation issue for the cur- rent medical imaging problems, specifically cancer detection and diagnosis, and shows very good performance and outperforms the state-of-art results in the literature. With the self-learned features, deep learning based techniques start to be applied to the biomedical imaging problems and various structures have been designed. In spite of its simplity and anticipated good performance, the deep learning based techniques can not perform to its best extent due to the limited size of data sets for the medical imaging problems. On the other side, the traditional hand-engineered features based methods have been studied in the past decades and a lot of useful features have been found by these research for the task of detecting and diagnosing the pulmonary nod- ules on CT scans, but these methods are usually performed through a series of complicated procedures with manually empirical parameter adjustments. Our method significantly reduces the complications of the traditional proce- dures for pulmonary nodules detection, while retaining and even outperforming the state-of-art accuracy. Besides, we make contribution on how to convert low-dose CT image to full-dose CT so as to adapting current models on the newly-emerged low-dose CT data

Complexity Reduction in Image-Based Breast Cancer Care

The diversity of malignancies of the breast requires personalized diagnostic and therapeutic decision making in a complex situation. This thesis contributes in three clinical areas: (1) For clinical diagnostic image evaluation, computer-aided detection and diagnosis of mass and non-mass lesions in breast MRI is developed. 4D texture features characterize mass lesions. For non-mass lesions, a combined detection/characterisation method utilizes the bilateral symmetry of the breast s contrast agent uptake. (2) To improve clinical workflows, a breast MRI reading paradigm is proposed, exemplified by a breast MRI reading workstation prototype. Instead of mouse and keyboard, it is operated using multi-touch gestures. The concept is extended to mammography screening, introducing efficient navigation aids. (3) Contributions to finite element modeling of breast tissue deformations tackle two clinical problems: surgery planning and the prediction of the breast deformation in a MRI biopsy device

Computer vision for sequential non-invasive microscopy imaging cytometry with applications in embryology

Many in vitro cytometric methods requires the sample to be destroyed in the process. Using image analysis of non-invasive microscopy techniques it is possible to monitor samples undisturbed in their natural environment, providing new insights into cell development, morphology and health. As the effect on the sample is minimized, imaging can be sustained for long un-interrupted periods of time, making it possible to study temporal events as well as individual cells over time. These methods are applicable in a number of fields, and are of particular importance in embryological studies, where no sample interference is acceptable. Using long term image capture and digital image cytometry of growing embryos it is possible to perform morphokinetic screening, automated analysis and annotation using proper software tools. By literature reference, one such framework is suggested and the required methods are developed and evaluated. Results are shown in tracking embryos, embryo cell segmentation, analysis of internal cell structures and profiling of cell growth and activity. Two related extensions of the framework into three dimensional embryo analysis and adherent cell monitoring are described

Segmentation and Characterization of Small Retinal Vessels in Fundus Images Using the Tensor Voting Approach

RÉSUMÉ La rétine permet de visualiser facilement une partie du réseau vasculaire humain. Elle offre ainsi un aperçu direct sur le développement et le résultat de certaines maladies liées au réseau vasculaire dans son entier. Chaque complication visible sur la rétine peut avoir un impact sur la capacité visuelle du patient. Les plus petits vaisseaux sanguins sont parmi les premières structures anatomiques affectées par la progression d’une maladie, être capable de les analyser est donc crucial. Les changements dans l’état, l’aspect, la morphologie, la fonctionnalité, ou même la croissance des petits vaisseaux indiquent la gravité des maladies. Le diabète est une maladie métabolique qui affecte des millions de personnes autour du monde. Cette maladie affecte le taux de glucose dans le sang et cause des changements pathologiques dans différents organes du corps humain. La rétinopathie diabétique décrit l’en- semble des conditions et conséquences du diabète au niveau de la rétine. Les petits vaisseaux jouent un rôle dans le déclenchement, le développement et les conséquences de la rétinopa- thie. Dans les dernières étapes de cette maladie, la croissance des nouveaux petits vaisseaux, appelée néovascularisation, présente un risque important de provoquer la cécité. Il est donc crucial de détecter tous les changements qui ont lieu dans les petits vaisseaux de la rétine dans le but de caractériser les vaisseaux sains et les vaisseaux anormaux. La caractérisation en elle-même peut faciliter la détection locale d’une rétinopathie spécifique. La segmentation automatique des structures anatomiques comme le réseau vasculaire est une étape cruciale. Ces informations peuvent être fournies à un médecin pour qu’elles soient considérées lors de son diagnostic. Dans les systèmes automatiques d’aide au diagnostic, le rôle des petits vaisseaux est significatif. Ne pas réussir à les détecter automatiquement peut conduire à une sur-segmentation du taux de faux positifs des lésions rouges dans les étapes ultérieures. Les efforts de recherche se sont concentrés jusqu’à présent sur la localisation précise des vaisseaux de taille moyenne. Les modèles existants ont beaucoup plus de difficultés à extraire les petits vaisseaux sanguins. Les modèles existants ne sont pas robustes à la grande variance d’apparence des vaisseaux ainsi qu’à l’interférence avec l’arrière-plan. Les modèles de la littérature existante supposent une forme générale qui n’est pas suffisante pour s’adapter à la largeur étroite et la courbure qui caractérisent les petits vaisseaux sanguins. De plus, le contraste avec l’arrière-plan dans les régions des petits vaisseaux est très faible. Les méthodes de segmentation ou de suivi produisent des résultats fragmentés ou discontinus. Par ailleurs, la segmentation des petits vaisseaux est généralement faite aux dépends de l’amplification du bruit. Les modèles déformables sont inadéquats pour segmenter les petits vaisseaux. Les forces utilisées ne sont pas assez flexibles pour compenser le faible contraste, la largeur, et vii la variance des vaisseaux. Enfin, les approches de type apprentissage machine nécessitent un entraînement avec une base de données étiquetée. Il est très difficile d’obtenir ces bases de données dans le cas des petits vaisseaux. Cette thèse étend les travaux de recherche antérieurs en fournissant une nouvelle mé- thode de segmentation des petits vaisseaux rétiniens. La détection de ligne à échelles multiples (MSLD) est une méthode récente qui démontre une bonne performance de segmentation dans les images de la rétine, tandis que le vote tensoriel est une méthode proposée pour reconnecter les pixels. Une approche combinant un algorithme de détection de ligne et de vote tensoriel est proposée. L’application des détecteurs de lignes a prouvé son efficacité à segmenter les vais- seaux de tailles moyennes. De plus, les approches d’organisation perceptuelle comme le vote tensoriel ont démontré une meilleure robustesse en combinant les informations voisines d’une manière hiérarchique. La méthode de vote tensoriel est plus proche de la perception humain que d’autres modèles standards. Comme démontré dans ce manuscrit, c’est un outil pour segmenter les petits vaisseaux plus puissant que les méthodes existantes. Cette combinaison spécifique nous permet de surmonter les défis de fragmentation éprouvés par les méthodes de type modèle déformable au niveau des petits vaisseaux. Nous proposons également d’utiliser un seuil adaptatif sur la réponse de l’algorithme de détection de ligne pour être plus robuste aux images non-uniformes. Nous illustrons également comment une combinaison des deux méthodes individuelles, à plusieurs échelles, est capable de reconnecter les vaisseaux sur des distances variables. Un algorithme de reconstruction des vaisseaux est également proposé. Cette dernière étape est nécessaire car l’information géométrique complète est requise pour pouvoir utiliser la segmentation dans un système d’aide au diagnostic. La segmentation a été validée sur une base de données d’images de fond d’oeil à haute résolution. Cette base contient des images manifestant une rétinopathie diabétique. La seg- mentation emploie des mesures de désaccord standards et aussi des mesures basées sur la perception. En considérant juste les petits vaisseaux dans les images de la base de données, l’amélioration dans le taux de sensibilité que notre méthode apporte par rapport à la méthode standard de détection multi-niveaux de lignes est de 6.47%. En utilisant les mesures basées sur la perception, l’amélioration est de 7.8%. Dans une seconde partie du manuscrit, nous proposons également une méthode pour caractériser les rétines saines ou anormales. Certaines images contiennent de la néovascula- risation. La caractérisation des vaisseaux en bonne santé ou anormale constitue une étape essentielle pour le développement d’un système d’aide au diagnostic. En plus des défis que posent les petits vaisseaux sains, les néovaisseaux démontrent eux un degré de complexité encore plus élevé. Ceux-ci forment en effet des réseaux de vaisseaux à la morphologie com- plexe et inhabituelle, souvent minces et à fortes courbures. Les travaux existants se limitent viii à l’utilisation de caractéristiques de premier ordre extraites des petits vaisseaux segmentés. Notre contribution est d’utiliser le vote tensoriel pour isoler les jonctions vasculaires et d’uti- liser ces jonctions comme points d’intérêts. Nous utilisons ensuite une statistique spatiale de second ordre calculée sur les jonctions pour caractériser les vaisseaux comme étant sains ou pathologiques. Notre méthode améliore la sensibilité de la caractérisation de 9.09% par rapport à une méthode de l’état de l’art. La méthode développée s’est révélée efficace pour la segmentation des vaisseaux réti- niens. Des tenseurs d’ordre supérieur ainsi que la mise en œuvre d’un vote par tenseur via un filtrage orientable pourraient être étudiés pour réduire davantage le temps d’exécution et résoudre les défis encore présents au niveau des jonctions vasculaires. De plus, la caractéri- sation pourrait être améliorée pour la détection de la rétinopathie proliférative en utilisant un apprentissage supervisé incluant des cas de rétinopathie diabétique non proliférative ou d’autres pathologies. Finalement, l’incorporation des méthodes proposées dans des systèmes d’aide au diagnostic pourrait favoriser le dépistage régulier pour une détection précoce des rétinopathies et d’autres pathologies oculaires dans le but de réduire la cessité au sein de la population.----------ABSTRACT As an easily accessible site for the direct observation of the circulation system, human retina can offer a unique insight into diseases development or outcome. Retinal vessels are repre- sentative of the general condition of the whole systematic circulation, and thus can act as a "window" to the status of the vascular network in the whole body. Each complication on the retina can have an adverse impact on the patient’s sight. In this direction, small vessels’ relevance is very high as they are among the first anatomical structures that get affected as diseases progress. Moreover, changes in the small vessels’ state, appearance, morphology, functionality, or even growth indicate the severity of the diseases. This thesis will focus on the retinal lesions due to diabetes, a serious metabolic disease affecting millions of people around the world. This disorder disturbs the natural blood glucose levels causing various pathophysiological changes in different systems across the human body. Diabetic retinopathy is the medical term that describes the condition when the fundus and the retinal vessels are affected by diabetes. As in other diseases, small vessels play a crucial role in the onset, the development, and the outcome of the retinopathy. More importantly, at the latest stage, new small vessels, or neovascularizations, growth constitutes a factor of significant risk for blindness. Therefore, there is a need to detect all the changes that occur in the small retinal vessels with the aim of characterizing the vessels to healthy or abnormal. The characterization, in turn, can facilitate the detection of a specific retinopathy locally, like the sight-threatening proliferative diabetic retinopathy. Segmentation techniques can automatically isolate important anatomical structures like the vessels, and provide this information to the physician to assist him in the final decision. In comprehensive systems for the automatization of DR detection, small vessels role is significant as missing them early in a CAD pipeline might lead to an increase in the false positive rate of red lesions in subsequent steps. So far, the efforts have been concentrated mostly on the accurate localization of the medium range vessels. In contrast, the existing models are weak in case of the small vessels. The required generalization to adapt an existing model does not allow the approaches to be flexible, yet robust to compensate for the increased variability in the appearance as well as the interference with the background. So far, the current template models (matched filtering, line detection, and morphological processing) assume a general shape for the vessels that is not enough to approximate the narrow, curved, characteristics of the small vessels. Additionally, due to the weak contrast in the small vessel regions, the current segmentation and the tracking methods produce fragmented or discontinued results. Alternatively, the small vessel segmentation can be accomplished at the expense of x background noise magnification, in the case of using thresholding or the image derivatives methods. Furthermore, the proposed deformable models are not able to propagate a contour to the full extent of the vasculature in order to enclose all the small vessels. The deformable model external forces are ineffective to compensate for the low contrast, the low width, the high variability in the small vessel appearance, as well as the discontinuities. Internal forces, also, are not able to impose a global shape constraint to the contour that could be able to approximate the variability in the appearance of the vasculature in different categories of vessels. Finally, machine learning approaches require the training of a classifier on a labelled set. Those sets are difficult to be obtained, especially in the case of the smallest vessels. In the case of the unsupervised methods, the user has to predefine the number of clusters and perform an effective initialization of the cluster centers in order to converge to the global minimum. This dissertation expanded the previous research work and provides a new segmentation method for the smallest retinal vessels. Multi-scale line detection (MSLD) is a recent method that demonstrates good segmentation performance in the retinal images, while tensor voting is a method first proposed for reconnecting pixels. For the first time, we combined the line detection with the tensor voting framework. The application of the line detectors has been proved an effective way to segment medium-sized vessels. Additionally, perceptual organization approaches like tensor voting, demonstrate increased robustness by combining information coming from the neighborhood in a hierarchical way. Tensor voting is closer than standard models to the way human perception functions. As we show, it is a more powerful tool to segment small vessels than the existing methods. This specific combination allows us to overcome the apparent fragmentation challenge of the template methods at the smallest vessels. Moreover, we thresholded the line detection response adaptively to compensate for non-uniform images. We also combined the two individual methods in a multi-scale scheme in order to reconnect vessels at variable distances. Finally, we reconstructed the vessels from their extracted centerlines based on pixel painting as complete geometric information is required to be able to utilize the segmentation in a CAD system. The segmentation was validated on a high-resolution fundus image database that in- cludes diabetic retinopathy images of varying stages, using standard discrepancy as well as perceptual-based measures. When only the smallest vessels are considered, the improve- ments in the sensitivity rate for the database against the standard multi-scale line detection method is 6.47%. For the perceptual-based measure, the improvement is 7.8% against the basic method. The second objective of the thesis was to implement a method for the characterization of isolated retinal areas into healthy or abnormal cases. Some of the original images, from which xi these patches are extracted, contain neovascularizations. Investigation of image features for the vessels characterization to healthy or abnormal constitutes an essential step in the direction of developing CAD system for the automatization of DR screening. Given that the amount of data will significantly increase under CAD systems, the focus on this category of vessels can facilitate the referral of sight-threatening cases to early treatment. In addition to the challenges that small healthy vessels pose, neovessels demonstrate an even higher degree of complexity as they form networks of convolved, twisted, looped thin vessels. The existing work is limited to the use of first-order characteristics extracted from the small segmented vessels that limits the study of patterns. Our contribution is in using the tensor voting framework to isolate the retinal vascular junctions and in turn using those junctions as points of interests. Second, we exploited second-order statistics computed on the junction spatial distribution to characterize the vessels as healthy or neovascularizations. In fact, the second-order spatial statistics extracted from the junction distribution are combined with widely used features to improve the characterization sensitivity by 9.09% over the state of art. The developed method proved effective for the segmentation of the retinal vessels. Higher order tensors along with the implementation of tensor voting via steerable filtering could be employed to further reduce the execution time, and resolve the challenges at vascular junctions. Moreover, the characterization could be advanced to the detection of prolifera- tive retinopathy by extending the supervised learning to include non-proliferative diabetic retinopathy cases or other pathologies. Ultimately, the incorporation of the methods into CAD systems could facilitate screening for the effective reduction of the vision-threatening diabetic retinopathy rates, or the early detection of other than ocular pathologies

A perceptual learning model to discover the hierarchical latent structure of image collections

Biology has been an unparalleled source of inspiration for the work of researchers in several scientific and engineering fields including computer vision. The starting point of this thesis is the neurophysiological properties of the human early visual system, in particular, the cortical mechanism that mediates learning by exploiting information about stimuli repetition. Repetition has long been considered a fundamental correlate of skill acquisition andmemory formation in biological aswell as computational learning models. However, recent studies have shown that biological neural networks have differentways of exploiting repetition in forming memory maps. The thesis focuses on a perceptual learning mechanism called repetition suppression, which exploits the temporal distribution of neural activations to drive an efficient neural allocation for a set of stimuli. This explores the neurophysiological hypothesis that repetition suppression serves as an unsupervised perceptual learning mechanism that can drive efficient memory formation by reducing the overall size of stimuli representation while strengthening the responses of the most selective neurons. This interpretation of repetition is different from its traditional role in computational learning models mainly to induce convergence and reach training stability, without using this information to provide focus for the neural representations of the data. The first part of the thesis introduces a novel computational model with repetition suppression, which forms an unsupervised competitive systemtermed CoRe, for Competitive Repetition-suppression learning. The model is applied to generalproblems in the fields of computational intelligence and machine learning. Particular emphasis is placed on validating the model as an effective tool for the unsupervised exploration of bio-medical data. In particular, it is shown that the repetition suppression mechanism efficiently addresses the issues of automatically estimating the number of clusters within the data, as well as filtering noise and irrelevant input components in highly dimensional data, e.g. gene expression levels from DNA Microarrays. The CoRe model produces relevance estimates for the each covariate which is useful, for instance, to discover the best discriminating bio-markers. The description of the model includes a theoretical analysis using Huber’s robust statistics to show that the model is robust to outliers and noise in the data. The convergence properties of themodel also studied. It is shown that, besides its biological underpinning, the CoRe model has useful properties in terms of asymptotic behavior. By exploiting a kernel-based formulation for the CoRe learning error, a theoretically sound motivation is provided for the model’s ability to avoid local minima of its loss function. To do this a necessary and sufficient condition for global error minimization in vector quantization is generalized by extending it to distance metrics in generic Hilbert spaces. This leads to the derivation of a family of kernel-based algorithms that address the local minima issue of unsupervised vector quantization in a principled way. The experimental results show that the algorithm can achieve a consistent performance gain compared with state-of-the-art learning vector quantizers, while retaining a lower computational complexity (linear with respect to the dataset size). Bridging the gap between the low level representation of the visual content and the underlying high-level semantics is a major research issue of current interest. The second part of the thesis focuses on this problem by introducing a hierarchical and multi-resolution approach to visual content understanding. On a spatial level, CoRe learning is used to pool together the local visual patches by organizing them into perceptually meaningful intermediate structures. On the semantical level, it provides an extension of the probabilistic Latent Semantic Analysis (pLSA) model that allows discovery and organization of the visual topics into a hierarchy of aspects. The proposed hierarchical pLSA model is shown to effectively address the unsupervised discovery of relevant visual classes from pictorial collections, at the same time learning to segment the image regions containing the discovered classes. Furthermore, by drawing on a recent pLSA-based image annotation system, the hierarchical pLSA model is extended to process and representmulti-modal collections comprising textual and visual data. The results of the experimental evaluation show that the proposed model learns to attach textual labels (available only at the level of the whole image) to the discovered image regions, while increasing the precision/ recall performance with respect to flat, pLSA annotation model

Stratégies efficaces en caractérisation des matériaux et calibration de modèles mécaniques pour la conception virtuelle des tôles métalliques

The mechanical design of sheet metal forming parts tends to be more virtual, reducing delays and manufacturing costs. Reliable numerical simulations can also lead to optimized metallic parts using accurately calibrated advanced constitutive models. Thus, the aim of this thesis is to improve the representation of the mechanical behavior of the material in the numerical model, by developing efficient and accurate methodologies to calibrate advanced constitutive models. A recent trend in material characterization is the use of a limited number of heterogeneous mechanical tests, which provide more valuable data than classical quasi-homogeneous tests. Yet, the design of the most suitable tests is still an open question. To that extent, an overview of heterogeneous mechanical tests for metallic sheets is provided. However, no standards exist for such tests, so specific metrics to analyze the achieved mechanical states are suggested and applied to four tests. Results show that the use of various metrics provides a good basis to qualitatively and quantitatively evaluate heterogeneous mechanical tests. Due to the development of full-field measurement techniques, it is possible to use heterogeneous mechanical tests to characterize the behavior of materials. However, no analytical solution exists between the measured fields and the material parameters. Inverse methodologies are required to calibrate constitutive models using an optimization algorithm to find the best material parameters. Most applications tend to use a gradient-based algorithm without exploring other possibilities. The performance of gradient-based and -free algorithms in the calibration of a thermoelastoviscoplastic model is discussed in terms of efficiency and robustness of the optimization process. Often, plane stress conditions are assumed in the calibration of constitutive models. Nevertheless, it is still unclear whether these are acceptable when dealing with large deformations. To further understand these limitations, the calibration of constitutive models is compared using the virtual fields method implemented in 2D and 3D frameworks. However, the 3D framework requires volumetric information of the kinematic fields, which is experimentally difficult to obtain. To address this constraint, an already existing volume reconstruction method, named internal mesh generation, is further improved to take into account strain gradients in the thickness. The uncertainty of the method is quantified through virtual experiments and synthetic images. Overall, the impact of this thesis is related to (i) the importance of establishing standard metrics in the selection and design of heterogeneous mechanical tests, and (ii) enhancing the calibration of advanced constitutive models from a 2D to a 3D framework.O projeto mecânico de peças por conformação de chapas metálicas tende a ser mais virtual, reduzindo atrasos e custos de produção. Simulações numéricas confiáveis também podem levar a peças optimizadas usando modelos constitutivos avançados calibrados com precisão. Assim, o objetivo desta tese é melhorar a representação do comportamento mecânico do material no modelo numérico, através do desenvolvimento de metodologias eficientes e precisas para a calibração de modelos constitutivos avançados. Uma tendência recente na caracterização de materiais é o uso de um número limitado de ensaios mecânicos heterogéneos, que fornecem dados mais valiosos do que os ensaios clássicos quase-homogéneos. No entanto, a concepção de ensaios mais adequados ainda é uma questão em aberto. Este trabalho detalha os ensaios mecânicos heterogêneos para chapas metálicas. No entanto, não existem ainda normas para estes ensaios, pelo que métricas específicas para analisar os estados mecânicos são sugeridas e aplicadas a quatro ensaios. Os resultados mostram que o uso de várias métricas disponibiliza uma boa base para avaliar ensaios mecânicos heterogéneos. Devido ao desenvolvimento de técnicas de medição de campo total, é possível utilizar ensaios mecânicos heterogéneos para caracterizar o comportamento dos materiais. No entanto, não existe uma solução analítica entre os campos medidos e os parâmetros do material. Metodologias inversas são necessárias para calibrar os modelos constitutivos usando um algoritmo de otimização para encontrar os melhores parâmetros do material. A maioria das aplicações tende a usar um algoritmo baseado em gradiente sem explorar outras possibilidades. O desempenho de vários algoritmos na calibração de um modelo termoelastoviscoplástico é discutido em termos de eficiência e robustez do processo de otimização. Frequentemente, são utilizadas condições de estado plano de tensão na calibração de modelos constitutivos, hipótese que é questionada quando se trata de grandes deformações. A calibração de modelos constitutivos é comparada usando o método de campos virtuais implementado em 2D e 3D. No entanto, a implementação 3D requer informações volumétricas dos campos cinemáticos, o que é experimentalmente difícil de obter. Um método de reconstrução volúmica já existente é melhorado para considerar os gradientes de deformação ao longo da espessura. A incerteza do método é quantificada através de ensaios virtuais e imagens sintéticas. No geral, o impacto desta tese está relacionado com (i) a importância de estabelecer métricas na seleção e concepção de ensaios mecânicos heterogéneos, e (ii) promover desenvolvimentos na calibração de modelos constitutivos avançados de 2D para 3D.La conception mécanique des pièces métalliques tend à être plus virtuelle, réduisant les délais et les coûts de fabrication. Des simulations numériques fiables peuvent conduire à des pièces optimisées en utilisant des modèles mécaniques avancés calibrés avec précision. Ainsi, l’objectif de cette thèse est d’améliorer la représentation du comportement mécanique du matériau dans le modèle numérique, en développant des méthodologies efficaces et précises pour calibrer des modèles de comportement avancés. Une tendance récente dans la caractérisation des matériaux est l’utilisation d’un nombre limité d’essais mécaniques hétérogènes, qui fournissent des données plus riches que les essais classiques quasi-homogènes. Pourtant, la conception des tests les plus adaptés reste une question ouverte. Ce tra- vail détaille les essais mécaniques hétérogènes pour les tôles métalliques. Cependant, aucune norme n’existe pour de tels tests, ainsi des métriques spécifiques pour analyser les états mécaniques sont suggérées et appliquées à quatre tests. Les résultats montrent que l’utilisation de diverses métriques fournit une bonne base pour évaluer des essais mécaniques hétérogènes. L’utilisation des essais mécaniques hétérogènes pour caractériser le com- portement des matériaux est rendue possible par des mesures de champ. Cependant, aucune solution analytique n’existe entre les champs mesurés et les paramètres du matériau. Des méthodologies inverses sont nécessaires pour calibrer les modèles de comportement à l’aide d’un algorithme d’optimi- sation afin de déterminer les meilleurs paramètres de matériau. Un algorithme basé sur le gradient est très fréquemment utilisé, sans explorer d’autres pos- sibilités. La performance de plusieurs algorithmes dans la calibration d’un modèle thermoélastoviscoplastique est discutée en termes d’efficacité et de robustesse du processus d’optimisation. Souvent, des conditions de contraintes planes sont supposées dans la cal- ibration des modèles, hypothèse qui est remise en cause dans le cas de forte localisation des déformations. La calibration de modèles de comporte- ment est comparée à l’aide de la méthode des champs virtuels développée dans les cadres 2D et 3D. Cependant, le cadre 3D nécessite des informations volumétriques des champs cinématiques, ce qui est expérimentalement dif- ficile à obtenir. Une méthode de reconstruction volumique déjà existante est encore améliorée pour prendre en compte les gradients de déformation dans l’épaisseur. L’incertitude de la méthode est quantifiée par des expériences virtuelles, à l’aide d’images de synthèse. Dans l’ensemble, l’impact de cette thèse est lié à (i) l’importance d’établir des métriques dans la sélection et la conception d’essais mécaniques hétérogènes, et (ii) à faire progresser la calibration de modèles de comportement avancés d’un cadre 2D à un cadre 3D.Programa Doutoral em Engenharia Mecânic