Medical image registration by neural networks: a regression-based registration approach

This thesis focuses on the development and evaluation of a registration-by-regression approach for the 3D/2D registration of coronary Computed Tomography Angiography (CTA) and X-ray angiography. This regression-based method relates image features of 2D projection images to the transformation parameters of the 3D image by a nonlinear regression. It treats registration as a regression problem, as an alternative for the traditional iterative approach that often comes with high computational costs and limited capture range. First we presented a survey of the methods with a regression-based registration approach for medical applications, as well as a summary of their main characteristics (Chapter 2). Second, we studied the registration methodology, addressing the input features and the choice of regression model (Chapter 3 and Chapter 4). For that purpose, we evaluated different options using simulated X-ray images generated from coronary artery tree models derived from 3D CTA scans. We also compared the registration-by-regression results with a method based on iterative optimization. Different image features of 2D projections and seven regression techniques were considered. The regression approach for simulated X-rays was shown to be slightly less accurate, but much more robust than the method based on an iterative optimization approach. Neural Networks obtained accurate results and showed to be robust to large initial misalignment. Third, we evaluated the registration-by-regression method using clinical data, integrating the 3D preoperative CTA of the coronary arteries with intraoperative 2D X-ray angiography images (Chapter 5). For the evaluation of the image registration, a gold standard registration was established using an exhaustive search followed by a multi-observer visual scoring procedure. The influence of preprocessing options for the simulated images and the real X-rays was studied. Several image features were also compared. The coronary registration–by-regression results were not satisfactory, resembling manual initialization accuracy. Therefore, the proposed method for this concrete problem and in its current configuration is not sufficiently accurate to be used in the clinical practice. The framework developed enables us to better understand the dependency of the proposed method on the differences between simulated and real images. The main difficulty lies in the substantial differences in appearance between the images used for training (simulated X-rays from 3D coronary models) and the actual images obtained during the intervention (real X-ray angiography). We suggest alternative solutions and recommend to evaluate the registration-by-regression approach in other applications where training data is available that has similar appearance to the eventual test data

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

Three-dimensional model-based analysis of vascular and cardiac images

This thesis is concerned with the geometrical modeling of organs to perform medical image analysis tasks. The thesis is divided in two main parts devoted to model linear vessel segments and the left ventricle of the heart, respectively. Chapters 2 to 4 present different aspects of a model-based technique for semi-automated quantification of linear vessel segments from 3-D Magnetic Resonance Angiography (MRA). Chapter 2 is concerned with a multiscale filter for the enhancement of vessels in 2-D and 3-D angiograms. Chapter 3 applies the filter developed in Chapter 2 to determine the central vessel axis in 3-D MRA images. This procedure is initialized using an efficient user interaction technique that naturally incorporates the knowledge of the operator about the vessel of interest. Also in this chapter, a linear vessel model is used to recover the position of the vessel wall in order to carry out an accurate quantitative analysis of vascular morphology. Prior knowledge is provided in two main forms: a cylindrical model introduces a shape prior while prior knowledge on the image acquisition (type of MRA technique) is used to define an appropriate vessel boundary criterion. In Chapter 4 an extensive in vitro and in vivo evaluation of the algorithm introduced in Chapter 3 is described. Chapters 5 to 7 change the focus to 3D cardiac image analysis from Magnetic Resonance Imaging. Chapter 5 presents an extensive survey, a categorization and a critical review of the field of cardiac modeling. Chapter 6 and Chapter 7 present successive refinements of a method for building statistical models of shape variability with particular emphasis on cardiac modeling. The method is based on an elastic registration method using hierarchical free-form deformations. A 3D shape model of the left and right ventricles of the heart was constructed. This model contains both the average shape of these organs as well as their shape variability. The methodology presented in the last two chapters could also be applied to other anatomical structures. This has been illustrated in Chapter 6 with examples of geometrical models of the nucleus caudate and the radius

Computational fluid dynamics indicators to improve cardiovascular pathologies

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.Postprint (published version