Image denoising based on nonlocal Bayesian singular value thresholding and Stein's unbiased risk estimator

© 1992-2012 IEEE. Singular value thresholding (SVT)- or nuclear norm minimization (NNM)-based nonlocal image denoising methods often rely on the precise estimation of the noise variance. However, most existing methods either assume that the noise variance is known or require an extra step to estimate it. Under the iterative regularization framework, the error in the noise variance estimate propagates and accumulates with each iteration, ultimately degrading the overall denoising performance. In addition, the essence of these methods is still least squares estimation, which can cause a very high mean-squared error (MSE) and is inadequate for handling missing data or outliers. In order to address these deficiencies, we present a hybrid denoising model based on variational Bayesian inference and Stein's unbiased risk estimator (SURE), which consists of two complementary steps. In the first step, the variational Bayesian SVT performs a low-rank approximation of the nonlocal image patch matrix to simultaneously remove the noise and estimate the noise variance. In the second step, we modify the conventional SURE full-rank SVT and its divergence formulas for rank-reduced eigen-triplets to remove the residual artifacts. The proposed hybrid BSSVT method achieves better performance in recovering the true image compared with state-of-the-art methods

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Generalizable automated pixel-level structural segmentation of medical and biological data

Over the years, the rapid expansion in imaging techniques and equipments has driven the demand for more automation in handling large medical and biological data sets. A wealth of approaches have been suggested as optimal solutions for their respective imaging types. These solutions span various image resolutions, modalities and contrast (staining) mechanisms. Few approaches generalise well across multiple image types, contrasts or resolution. This thesis proposes an automated pixel-level framework that addresses 2D, 2D+t and 3D structural segmentation in a more generalizable manner, yet has enough adaptability to address a number of specific image modalities, spanning retinal funduscopy, sequential fluorescein angiography and two-photon microscopy. The pixel-level segmentation scheme involves: i ) constructing a phase-invariant orientation field of the local spatial neighbourhood; ii ) combining local feature maps with intensity-based measures in a structural patch context; iii ) using a complex supervised learning process to interpret the combination of all the elements in the patch in order to reach a classification decision. This has the advantage of transferability from retinal blood vessels in 2D to neural structures in 3D. To process the temporal components in non-standard 2D+t retinal angiography sequences, we first introduce a co-registration procedure: at the pairwise level, we combine projective RANSAC with a quadratic homography transformation to map the coordinate systems between any two frames. At the joint level, we construct a hierarchical approach in order for each individual frame to be registered to the global reference intra- and inter- sequence(s). We then take a non-training approach that searches in both the spatial neighbourhood of each pixel and the filter output across varying scales to locate and link microvascular centrelines to (sub-) pixel accuracy. In essence, this \link while extract" piece-wise segmentation approach combines the local phase-invariant orientation field information with additional local phase estimates to obtain a soft classification of the centreline (sub-) pixel locations. Unlike retinal segmentation problems where vasculature is the main focus, 3D neural segmentation requires additional exibility, allowing a variety of structures of anatomical importance yet with different geometric properties to be differentiated both from the background and against other structures. Notably, cellular structures, such as Purkinje cells, neural dendrites and interneurons, all display certain elongation along their medial axes, yet each class has a characteristic shape captured by an orientation field that distinguishes it from other structures. To take this into consideration, we introduce a 5D orientation mapping to capture these orientation properties. This mapping is incorporated into the local feature map description prior to a learning machine. Extensive performance evaluations and validation of each of the techniques presented in this thesis is carried out. For retinal fundus images, we compute Receiver Operating Characteristic (ROC) curves on existing public databases (DRIVE & STARE) to assess and compare our algorithms with other benchmark methods. For 2D+t retinal angiography sequences, we compute the error metrics ("Centreline Error") of our scheme with other benchmark methods. For microscopic cortical data stacks, we present segmentation results on both surrogate data with known ground-truth and experimental rat cerebellar cortex two-photon microscopic tissue stacks.Open Acces

Anatomical Modeling of Cerebral Microvascular Structures: Application to Identify Biomarkers of Microstrokes

Les réseaux microvasculaires corticaux sont responsables du transport de l’oxygène et des substrats énergétiques vers les neurones. Ces réseaux réagissent dynamiquement aux demandes énergétiques lors d’une activation neuronale par le biais du couplage neurovasculaire. Afin d’élucider le rôle de la composante microvasculaire dans ce processus de couplage, l’utilisation de la modélisation in-formatique pourrait se révéler un élément clé. Cependant, la manque de méthodologies de calcul appropriées et entièrement automatisées pour modéliser et caractériser les réseaux microvasculaires reste l’un des principaux obstacles. Le développement d’une solution entièrement automatisée est donc important pour des explorations plus avancées, notamment pour quantifier l’impact des mal-formations vasculaires associées à de nombreuses maladies cérébrovasculaires. Une observation courante dans l’ensemble des troubles neurovasculaires est la formation de micro-blocages vascu-laires cérébraux (mAVC) dans les artérioles pénétrantes de la surface piale. De récents travaux ont démontré l’impact de ces événements microscopiques sur la fonction cérébrale. Par conséquent, il est d’une importance vitale de développer une approche non invasive et comparative pour identifier leur présence dans un cadre clinique. Dans cette thèse,un pipeline de traitement entièrement automatisé est proposé pour aborder le prob-lème de la modélisation anatomique microvasculaire. La méthode de modélisation consiste en un réseau de neurones entièrement convolutif pour segmenter les capillaires sanguins, un générateur de modèle de surface 3D et un algorithme de contraction de la géométrie pour produire des mod-èles graphiques vasculaires ne comportant pas de connections multiples. Une amélioration de ce pipeline est développée plus tard pour alléger l’exigence de maillage lors de la phase de représen-tation graphique. Un nouveau schéma permettant de générer un modèle de graphe est développé avec des exigences d’entrée assouplies et permettant de retenir les informations sur les rayons des vaisseaux. Il est inspiré de graphes géométriques déformants construits en respectant les morpholo-gies vasculaires au lieu de maillages de surface. Un mécanisme pour supprimer la structure initiale du graphe à chaque exécution est implémenté avec un critère de convergence pour arrêter le pro-cessus. Une phase de raffinement est introduite pour obtenir des modèles vasculaires finaux. La modélisation informatique développée est ensuite appliquée pour simuler les signatures IRM po-tentielles de mAVC, combinant le marquage de spin artériel (ASL) et l’imagerie multidirectionnelle pondérée en diffusion (DWI). L’hypothèse est basée sur des observations récentes démontrant une réorientation radiale de la microvascularisation dans la périphérie du mAVC lors de la récupéra-tion chez la souris. Des lits capillaires synthétiques, orientés aléatoirement et radialement, et des angiogrammes de tomographie par cohérence optique (OCT), acquis dans le cortex de souris (n = 5) avant et après l’induction d’une photothrombose ciblée, sont analysés. Les graphes vasculaires informatiques sont exploités dans un simulateur 3D Monte-Carlo pour caractériser la réponse par résonance magnétique (MR), tout en considérant les effets des perturbations du champ magnétique causées par la désoxyhémoglobine, et l’advection et la diffusion des spins nucléaires. Le pipeline graphique proposé est validé sur des angiographies synthétiques et réelles acquises avec différentes modalités d’imagerie. Comparé à d’autres méthodes effectuées dans le milieu de la recherche, les expériences indiquent que le schéma proposé produit des taux d’erreur géométriques et topologiques amoindris sur divers angiogrammes. L’évaluation confirme également l’efficacité de la méthode proposée en fournissant des modèles représentatifs qui capturent tous les aspects anatomiques des structures vasculaires. Ensuite, afin de trouver des signatures de mAVC basées sur le signal IRM, la modélisation vasculaire proposée est exploitée pour quantifier le rapport de perte de signal intravoxel minimal lors de l’application de plusieurs directions de gradient, à des paramètres de séquence variables avec et sans ASL. Avec l’ASL, les résultats démontrent une dif-férence significative (p <0,05) entre le signal calculé avant et 3 semaines après la photothrombose. La puissance statistique a encore augmenté (p <0,005) en utilisant des angiogrammes capturés à la semaine suivante. Sans ASL, aucun changement de signal significatif n’est trouvé. Des rapports plus élevés sont obtenus à des intensités de champ magnétique plus faibles (par exemple, B0 = 3) et une lecture TE plus courte (<16 ms). Cette étude suggère que les mAVC pourraient être carac-térisés par des séquences ASL-DWI, et fournirait les informations nécessaires pour les validations expérimentales postérieures et les futurs essais comparatifs.----------ABSTRACT Cortical microvascular networks are responsible for carrying the necessary oxygen and energy substrates to our neurons. These networks react to the dynamic energy demands during neuronal activation through the process of neurovascular coupling. A key element in elucidating the role of the microvascular component in the brain is through computational modeling. However, the lack of fully-automated computational frameworks to model and characterize these microvascular net-works remains one of the main obstacles. Developing a fully-automated solution is thus substantial for further explorations, especially to quantify the impact of cerebrovascular malformations associ-ated with many cerebrovascular diseases. A common pathogenic outcome in a set of neurovascular disorders is the formation of microstrokes, i.e., micro occlusions in penetrating arterioles descend-ing from the pial surface. Recent experiments have demonstrated the impact of these microscopic events on brain function. Hence, it is of vital importance to develop a non-invasive and translatable approach to identify their presence in a clinical setting. In this thesis, a fully automatic processing pipeline to address the problem of microvascular anatom-ical modeling is proposed. The modeling scheme consists of a fully-convolutional neural network to segment microvessels, a 3D surface model generator and a geometry contraction algorithm to produce vascular graphical models with a single connected component. An improvement on this pipeline is developed later to alleviate the requirement of water-tight surface meshes as inputs to the graphing phase. The novel graphing scheme works with relaxed input requirements and intrin-sically captures vessel radii information, based on deforming geometric graphs constructed within vascular boundaries instead of surface meshes. A mechanism to decimate the initial graph struc-ture at each run is formulated with a convergence criterion to stop the process. A refinement phase is introduced to obtain final vascular models. The developed computational modeling is then ap-plied to simulate potential MRI signatures of microstrokes, combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). The hypothesis is driven based on recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially oriented, and op-tical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n=5) before and after inducing targeted photothrombosis, are analyzed. The computational vascular graphs are exploited within a 3D Monte-Carlo simulator to characterize the magnetic resonance (MR) re-sponse, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. The proposed graphing pipeline is validated on both synthetic and real angiograms acquired with different imaging modalities. Compared to other efficient and state-of-the-art graphing schemes, the experiments indicate that the proposed scheme produces the lowest geometric and topological error rates on various angiograms. The evaluation also confirms the efficiency of the proposed scheme in providing representative models that capture all anatomical aspects of vascular struc-tures. Next, searching for MRI-based signatures of microstokes, the proposed vascular modeling is exploited to quantify the minimal intravoxel signal loss ratio when applying multiple gradient di-rections, at varying sequence parameters with and without ASL. With ASL, the results demonstrate a significant difference (p<0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p<0.005) using angiograms captured at week 4. Without ASL, no reliable signal change is found. Higher ratios with improved significance are achieved at low magnetic field strengths (e.g., at 3 Tesla) and shorter readout TE (<16 ms). This study suggests that microstrokes might be characterized through ASL-DWI sequences, and provides necessary insights for posterior experimental validations, and ultimately, future transla-tional trials

Fusion of magnetic resonance and ultrasound images for endometriosis detection

Endometriosis is a gynecologic disorder that typically affects women in their reproductive age and is associated with chronic pelvic pain and infertility. In the context of pre-operative diagnosis and guided surgery, endometriosis is a typical example of pathology that requires the use of both magnetic resonance (MR) and ultrasound (US) modalities. These modalities are used side by sidebecause they contain complementary information. However, MRI and US images have different spatial resolutions, fields of view and contrasts and are corrupted by different kinds of noise, which results in important challenges related to their analysis by radiologists. The fusion of MR and US images is a way of facilitating the task of medical experts and improve the pre-operative diagnosis and the surgery mapping. The object of this PhD thesis is to propose a new automatic fusion method for MRI and US images. First, we assume that the MR and US images to be fused are aligned, i.e., there is no geometric distortion between these images. We propose a fusion method for MR and US images, which aims at combining the advantages of each modality, i.e., good contrast and signal to noise ratio for the MR image and good spatial resolution for the US image. The proposed algorithm is based on an inverse problem, performing a super-resolution of the MR image and a denoising of the US image. A polynomial function is introduced to modelthe relationships between the gray levels of the MR and US images. However, the proposed fusion method is very sensitive to registration errors. Thus, in a second step, we introduce a joint fusion and registration method for MR and US images. Registration is a complicated task in practical applications. The proposed MR/US image fusion performs jointly super-resolution of the MR image and despeckling of the US image, and is able to automatically account for registration errors. A polynomial function is used to link ultrasound and MR images in the fusion process while an appropriate similarity measure is introduced to handle the registration problem. The proposed registration is based on a non-rigid transformation containing a local elastic B-spline model and a global affine transformation. The fusion and registration operations are performed alternatively simplifying the underlying optimization problem. The interest of the joint fusion and registration is analyzed using synthetic and experimental phantom images

Applications of Deep Learning in Medical Image Analysis : Grading of Prostate Cancer and Detection of Coronary Artery Disease

A wide range of medical examinations are using analysis of images from different types of equipment. Using artificial intelligence, the assessments could be done automatically. This can have multiple benefits for the healthcare; reduce workload for medical doctors, decrease variations in diagnoses and cut waiting times for the patient as well as improve the performance. The aim of this thesis has been to develop such solutions for two common diseases: prostate cancer and coronary artery disease. The methods used are mainly based on deep learning, where the model teaches itself by training on large datasets.Prostate cancer is one of the most common cancer diagnoses among men. The diagnosis is most commonly determined by visual assessment of prostate biopsies in a light microscope according to the Gleason scale. Deep learning methods to automatically detect and grade the cancer areas are presented in this thesis. The methods have been adapted to improve the generalisation performance on images from different hospitals, images which have inevitable variations in e.g.\ stain appearance. The methods include the usage of digital stain normalisation, training with extensive augmentation or using models such as a domain-adversarial neural network. One Gleason grading algorithm was evaluated on a small cohort with biopsies annotated in detail by two pathologists, to compare the performance with pathologists' inter-observer variability. Another cancer detection algorithm was evaluated on a large active surveillance cohort, containing patients with small areas of low-grade cancer. The results are promising towards a future tool to facilitate grading of prostate cancer.Cardiovascular disease is the leading cause of death world-wide, whereof coronary artery disease is one of the most common diseases. One way to diagnose coronary artery disease is by using myocardial perfusion imaging, where disease in the three main arteries supplying the heart with blood can be detected. Methods based on deep learning to perform the detection automatically are presented in this thesis. Furthermore, an algorithm developed to predict the degree of coronary artery stenosis from myocardial perfusion imaging, by means of quantitative coronary angiography, has also been developed. This assessment is normally done using invasive coronary angiography. Making the prediction automatically from myocardial perfusion imaging could save suffering for patients and free resources within the healthcare system

Review on retrospective procedures to correct retinal motion artefacts in OCT imaging

Motion artefacts from involuntary changes in eye fixation remain a major imaging issue in optical coherence tomography (OCT). This paper reviews the state-of-the-art of retrospective procedures to correct retinal motion and axial eye motion artefacts in OCT imaging. Following an overview of motion induced artefacts and correction strategies, a chronological survey of retrospective approaches since the introduction of OCT until the current days is presented. Pre-processing, registration, and validation techniques are described. The review finishes by discussing the limitations of the current techniques and the challenges to be tackled in future developments