Fully-automated Body Composition Analysis in Routine CT Imaging Using 3D Semantic Segmentation Convolutional Neural Networks

Body tissue composition is a long-known biomarker with high diagnostic and prognostic value in cardiovascular, oncological and orthopaedic diseases, but also in rehabilitation medicine or drug dosage. In this study, the aim was to develop a fully automated, reproducible and quantitative 3D volumetry of body tissue composition from standard CT examinations of the abdomen in order to be able to offer such valuable biomarkers as part of routine clinical imaging. Therefore an in-house dataset of 40 CTs for training and 10 CTs for testing were fully annotated on every fifth axial slice with five different semantic body regions: abdominal cavity, bones, muscle, subcutaneous tissue, and thoracic cavity. Multi-resolution U-Net 3D neural networks were employed for segmenting these body regions, followed by subclassifying adipose tissue and muscle using known hounsfield unit limits. The S{\o}rensen Dice scores averaged over all semantic regions was 0.9553 and the intra-class correlation coefficients for subclassified tissues were above 0.99. Our results show that fully-automated body composition analysis on routine CT imaging can provide stable biomarkers across the whole abdomen and not just on L3 slices, which is historically the reference location for analysing body composition in the clinical routine

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Méthodes multi-organes rapides avec a priori de forme pour la localisation et la segmentation en imagerie médicale 3D

With the ubiquity of imaging in medical applications (diagnostic, treatment follow-up, surgery planning. . . ), image processing algorithms have become of primary importance. Algorithms help clinicians extract critical information more quickly and more reliably from increasingly large and complex acquisitions. In this context, anatomy localization and segmentation is a crucial component in modern clinical workflows. Due to particularly high requirements in terms of robustness, accuracy and speed, designing such tools remains a challengingtask.In this work, we propose a complete pipeline for the segmentation of multiple organs in medical images. The method is generic, it can be applied to varying numbers of organs, on different imaging modalities. Our approach consists of three components: (i) an automatic localization algorithm, (ii) an automatic segmentation algorithm, (iii) a framework for interactive corrections. We present these components as a coherent processing chain, although each block could easily be used independently of the others. To fulfill clinical requirements, we focus on robust and efficient solutions. Our anatomy localization method is based on a cascade of Random Regression Forests (Cuingnet et al., 2012). One key originality of our work is the use of shape priors for each organ (thanks to probabilistic atlases). Combined with the evaluation of the trained regression forests, they result in shape-consistent confidence maps for each organ instead of simple bounding boxes. Our segmentation method extends the implicit template deformation framework of Mory et al. (2012) to multiple organs. The proposed formulation builds on the versatility of the original approach and introduces new non-overlapping constraintsand contrast-invariant forces. This makes our approach a fully automatic, robust and efficient method for the coherent segmentation of multiple structures. In the case of imperfect segmentation results, it is crucial to enable clinicians to correct them easily. We show that our automatic segmentation framework can be extended with simple user-driven constraints to allow for intuitive interactive corrections. We believe that this final component is key towards the applicability of our pipeline in actual clinical routine.Each of our algorithmic components has been evaluated on large clinical databases. We illustrate their use on CT, MRI and US data and present a user study gathering the feedback of medical imaging experts. The results demonstrate the interest in our method and its potential for clinical use.Avec l’utilisation de plus en plus répandue de l’imagerie dans la pratique médicale (diagnostic, suivi, planification d’intervention, etc.), le développement d’algorithmes d’analyse d’images est devenu primordial. Ces algorithmes permettent aux cliniciens d’analyser et d’interpréter plus facilement et plus rapidement des données de plus en plus complexes. Dans ce contexte, la localisation et la segmentation de structures anatomiques sont devenues des composants critiques dans les processus cliniques modernes. La conception de tels outils pour répondre aux exigences de robustesse, précision et rapidité demeure cependant un réel défi technique.Ce travail propose une méthode complète pour la segmentation de plusieurs organes dans des images médicales. Cette méthode, générique et pouvant être appliquée à un nombre varié de structures et dans différentes modalités d’imagerie, est constituée de trois composants : (i) un algorithme de localisation automatique, (ii) un algorithme de segmentation, (iii) un outil de correction interactive. Ces différentes parties peuvent s’enchaîner aisément pour former un outil complet et cohérent, mais peuvent aussi bien être utilisées indépendemment. L’accent a été mis sur des méthodes robustes et efficaces afin de répondre aux exigences cliniques. Notre méthode de localisation s’appuie sur une cascade de régression par forêts aléatoires (Cuingnet et al., 2012). Elle introduit l’utilisation d’informations a priori de forme, spécifiques à chaque organe (grâce à des atlas probabilistes) pour des résultats plus cohérents avec la réalité anatomique. Notre méthode de segmentation étend la méthode de segmentation par modèle implicite (Mory et al., 2012) à plusieurs modèles. La formulation proposée permet d’obtenir des déformations cohérentes, notamment en introduisant des contraintes de non recouvrement entre les modèles déformés. En s’appuyant sur des forces images polyvalentes, l’approche proposée se montre robuste et performante pour la segmentation de multiples structures. Toute méthode automatique n’est cependant jamais parfaite. Afin que le clinicien garde la main sur le résultat final, nous proposons d’enrichir la formulation précédente avec des contraintes fournies par l’utilisateur. Une optimisation localisée permet d’obtenir un outil facile à utiliser et au comportement intuitif. Ce dernier composant est crucial pour que notre outil soit réellement utilisable en pratique. Chacun de ces trois composants a été évalué sur plusieurs grandes bases de données cliniques (en tomodensitométrie, imagerie par résonance magnétique et ultrasons). Une étude avec des utilisateurs nous a aussi permis de recueillir des retours positifs de plusieurs experts en imagerie médicale. Les différents résultats présentés dans ce manuscrit montrent l’intérêt de notre méthode et son potentiel pour une utilisation clinique

Combining global and local information for the segmentation of MR images of the brain

Magnetic resonance imaging can provide high resolution volumetric images of the brain with exceptional soft tissue contrast. These factors allow the complex structure of the brain to be clearly visualised. This has lead to the development of quantitative methods to analyse neuroanatomical structures. In turn, this has promoted the use of computational methods to automate and improve these techniques. This thesis investigates methods to accurately segment MRI images of the brain. The use of global and local image information is considered, where global information includes image intensity distributions, means and variances and local information is based on the relationship between spatially neighbouring voxels. Methods are explored that aim to improve the classification and segmentation of MR images of the brain by combining these elements. Some common artefacts exist in MR brain images that can be seriously detrimental to image analysis methods. Methods to correct for these artifacts are assessed by exploring their effect, first with some well established classification methods and then with methods that combine global information with local information in the form of a Markov random field model. Another characteristic of MR images is the partial volume effect that occurs where signals from different tissues become mixed over the finite volume of a voxel. This effect is demonstrated and quantified using a simulation. Analysis methods that address these issues are tested on simulated and real MR images. They are also applied to study the structure of the temporal lobes in a group of patients with temporal lobe epilepsy. The results emphasise the benefits and limitations of applying these methods to a problem of this nature. The work in this thesis demonstrates the advantages of using global and local information together in the segmentation of MR brain images and proposes a generalised framework that allows this information to be combined in a flexible way

Motion Tracking for Medical Applications using Hierarchical Filter Models

A medical intervention often requires relating treatment to the situation, which it was planned on. In order to circumvent undesirable effects of motion during the intervention, positional differences must be detected in real-time. To this end, in this thesis a hierarchical Particle Filter based tracking algorithm is developed in three stages. Initially, a model description of the individual nodes in the aspired hierarchical tree is presented. Using different approaches, properties of such a node are derived and approximated, leading to a parametrization scheme. Secondly, transformations and appearance of the data are described by a fixed hierarchical tree. A sparse description for typical landmarks in medical image data is presented. A static tree model with two levels is developed and investigated. Finally, the notion of 'association' between landmarks and nodes is introduced in order to allow for dynamic adaptation to the underlying structure of the data. Processes for tree maintenance using clustering and sequential reinforcement are implemented. The function of the full algorithm is demonstrated on data of abdominal breathing motion

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Gaze-Based Human-Robot Interaction by the Brunswick Model

We present a new paradigm for human-robot interaction based on social signal processing, and in particular on the Brunswick model. Originally, the Brunswick model copes with face-to-face dyadic interaction, assuming that the interactants are communicating through a continuous exchange of non verbal social signals, in addition to the spoken messages. Social signals have to be interpreted, thanks to a proper recognition phase that considers visual and audio information. The Brunswick model allows to quantitatively evaluate the quality of the interaction using statistical tools which measure how effective is the recognition phase. In this paper we cast this theory when one of the interactants is a robot; in this case, the recognition phase performed by the robot and the human have to be revised w.r.t. the original model. The model is applied to Berrick, a recent open-source low-cost robotic head platform, where the gazing is the social signal to be considered

Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts