L'objectif de cette thèse est de s'intéresser à la classification de cellules et de tissus au sein d'images d'origine biomédicales en s'appuyant sur des critères morphologiques. Le but est de permettre aux médecins et aux biologistes de mieux comprendre les lois qui régissent certains phénomènes biologiques. Ce travail se décompose en trois principales parties correspondant aux trois problèmes typiques des divers domaines de l'imagerie biomédicale abordés. L'objet de la première est l'analyse de vidéos d'endomicroscopie du colon dans lesquelles il s'agit de déterminer automatiquement la classe pathologique des polypes qu'on y observe. Cette tâche est réalisée par un apprentissage supervisé multiclasse couplant les séparateurs à vaste marge à des outils de théorie des graphes. La deuxième partie s'intéresse à l'étude de la morphologie de neurones de souris observés par microscopie confocale en fluorescence. Afin de disposer d'une information riche, les neurones sont observés à deux grossissements, l'un permettant de bien caractériser les corps cellulaires, l'autre, plus faible, pour voir les dendrites apicales dans leur intégralité. Sur ces images, des descripteurs morphologiques des neurones sont extraits automatiquement en vue d'une classification. La dernière partie concerne le traitement multi-échelle d'images d'histologie digitale dans le contexte du cancer du rein. Le réseau vasculaire est extrait et mis sous forme de graphe afin de pouvoir établir un lien entre l'architecture vasculaire de la tumeur et sa classe pathologique. / The purpose of this Ph.D. thesis is to study the classification based on morphological features of cells and tissues taken from biomedical images. The goal is to help medical doctors and biologists better understand some biological phenomena. This work is spread in three main parts corresponding to the three typical problems in biomedical imaging tackled. The first part consists in analyzing endomicroscopic videos of the colon in which the pathological class of the polyps has to be determined. This task is performed using a supervised multiclass machine learning algorithm combining support vector machines and graph theory tools. The second part concerns the study of the morphology of mice neurons taken from fluorescent confocal microscopy. In order to obtain a rich information, the neurons are imaged at two different magnifications, the higher magnification where the soma appears in details, and the lower showing the whole cortex, including the apical dendrites. On these images, morphological features are automatically extracted with the intention of performing a classification. The last part is about the multi-scale processing of digital histology images in the context of kidney cancer. The vascular network is extracted and modeled by a graph to establish a link between the architecture of the tumor and its pathological class.

Knowledge of the microcirculatory system has added significant value to the analysis of tissue oxygenation and perfusion. While developments in videomicroscopy technology have enabled medical researchers and physicians to observe the microvascular system, the available software tools are limited in their capabilities to determine quantitative features of microcirculation, either automatically or accurately. In particular, microvessel density has been a critical diagnostic measure in evaluating disease progression and a prognostic indicator in various clinical conditions. As a result, automated analysis of the microcirculatory system can be substantially beneficial in various real-time and off-line therapeutic medical applications, such as optimization of resuscitation. This study focuses on the development of an algorithm to automatically segment microvessels, calculate the density of capillaries in microcirculatory videos, and determine the distribution of blood circulation. The proposed technique is divided into four major steps: video stabilization, video enhancement, segmentation and post-processing. The stabilization step estimates motion and corrects for the motion artifacts using an appropriate motion model. Video enhancement improves the visual quality of video frames through preprocessing, vessel enhancement and edge enhancement. The resulting frames are combined through an adjusted weighted median filter and the resulting frame is then thresholded using an entropic thresholding technique. Finally, a region growing technique is utilized to correct for the discontinuity of blood vessels. Using the final binary results, the most commonly used measure for the assessment of microcirculation, i.e. Functional Capillary Density (FCD), is calculated. The designed technique is applied to video recordings of healthy and diseased human and animal samples obtained by MicroScan device based on Sidestream Dark Field (SDF) imaging modality. To validate the final results, the calculated FCD results are compared with the results obtained by blind detailed inspection of three medical experts, who have used AVA (Automated Vascular Analysis) semi-automated microcirculation analysis software. Since there is neither a fully automated accurate microcirculation analysis program, nor a publicly available annotated database of microcirculation videos, the results acquired by the experts are considered the gold standard. Bland-Altman plots show that there is ``Good Agreement" between the results of the algorithm and that of gold standard. In summary, the main objective of this study is to eliminate the need for human interaction to edit/ correct results, to improve the accuracy of stabilization and segmentation, and to reduce the overall computation time. The proposed methodology impacts the field of computer science through development of image processing techniques to discover the knowledge in grayscale video frames. The broad impact of this work is to assist physicians, medical researchers and caregivers in making diagnostic and therapeutic decisions for microcirculatory abnormalities and in studying of the human microcirculation.

<p>Quick and accurate segmentation and object detection of the biomedical image is the starting point of most disease analysis and understanding of biological processes in medical research. It will enhance drug development and advance medical treatment, especially in cancer-related diseases. However, identifying the objects in the CT or MRI images and labeling them usually takes time even for an experienced person. Currently, there is no automatic detection technique for nucleus identification, pneumonia detection, and fetus brain segmentation. Fortunately, as the successful application of artificial intelligence (AI) in image processing, many challenging tasks are easily solved with deep convolutional neural networks. In light of this, in this thesis, the deep learning based object detection and segmentation methods were implemented to perform the nucleus segmentation, lung segmentation, pneumonia detection, and fetus brain segmentation. The semantic segmentation is achieved by the customized U-Net model, and the instance localization is achieved by Faster R-CNN. The reason we choose U-Net is that such a network can be trained end-to-end, which means the architecture of this network is very simple, straightforward and fast to train. Besides, for this project, the availability of the dataset is limited, which makes U-Net a more suitable choice. We also implemented the Faster R-CNN to achieve the object localization. Finally, we evaluated the performance of the two models and further compared the pros and cons of them. The preliminary results show that deep learning based technique outperforms all existing traditional segmentation algorithms. </p>

This thesis addresses three problems related to image registration, prediction and tracking, applied to Angiography and Oncology. For image analysis, various probabilistic models have been employed to characterize the image deformations, target motions and state estimations. (i) In Digital Subtraction Angiography (DSA), having a high quality visualization of the blood motion in the vessels is essential both in diagnostic and interventional applications. In order to reduce the inherent movement artifacts in DSA, non-rigid image registration is used before subtracting the mask from the contrast image. DSA image registration is a challenging problem, as it requires non-rigid matching across spatially non-uniform control points, at high speed. We model the problem of sub-pixel matching, as a labeling problem on a non-uniform Markov Random Field (MRF). We use quad-trees in a novel way to generate the non uniform grid structure and optimize the registration cost using graph-cuts technique. The MRF formulation produces a smooth displacement field which results in better artifact reduction than with the conventional approach of independently registering the control points. The above approach is further improved using two models. First, we introduce the concept of pivotal and non-pivotal control points. `Pivotal control points' are nodes in the Markov network that are close to the edges in the mask image, while 'non-pivotal control points' are identified in soft tissue regions. This model leads to a novel MRF framework and energy formulation. Next, we propose a Gaussian MRF model and solve the energy minimization problem for sub-pixel DSA registration using Random Walker (RW). An incremental registration approach is developed using quad-tree based MRF structure and RW, wherein the density of control points is hierarchically increased at each level M depending of the features to be used and the required accuracy. A novel numbering scheme of the control points allows us to reuse the computations done at level M in M + 1. Both the models result in an accelerated performance without compromising on the artifact reduction. We have also provided a CUDA based design of the algorithm, and shown performance acceleration on a GPU. We have tested the approach using 25 clinical data sets, and have presented the results of quantitative analysis and clinical assessment. (ii) In External Beam Radiation Therapy (EBRT), in order to monitor the intra fraction motion of thoracic and abdominal tumors, the lung diaphragm apex can be used as an internal marker. However, tracking the position of the apex from image based observations is a challenging problem, as it undergoes both position and shape variation. We propose a novel approach for tracking the ipsilateral hemidiaphragm apex (IHDA) position on CBCT projection images. We model the diaphragm state as a spatiotemporal MRF, and obtain the trace of the apex by solving an energy minimization problem through graph-cuts. We have tested the approach using 15 clinical data sets and found that this approach outperforms the conventional full search method in terms of accuracy. We have provided a GPU based heterogeneous implementation of the algorithm using CUDA to increase the viability of the approach for clinical use. (iii) In an adaptive radiotherapy system, irrespective of the methods used for target observations there is an inherent latency in the beam control as they involve mechanical movement and processing delays. Hence predicting the target position during `beam on target' is essential to increase the control precision. We propose a novel prediction model (called o set sine model) for the breathing pattern. We use IHDA positions (from CBCT images) as measurements and an Unscented Kalman Filter (UKF) for state estimation. The results based on 15 clinical datasets show that, o set sine model outperforms the state of the art LCM model in terms of prediction accuracy.