Motion tracking tMRI datasets to quantify abnormal left ventricle motion using finite element modelling

According to `The Atlas of Heart Disease and Stroke'[MMMG04] published by the World Health Organization, heart disease accounts for nearly half the deaths in both the developed and developing countries and is the world's single biggest killer. However, early detection of a diseased heart condition can prevent many of these fatalities. Regional wall motion abnormalities of the heart precede both ECG abnormalities and chest pain as an indicator of myocardial ischaemia and are an excellent indicator of coronary stenosis [GZM97]. These motion abnormalities of the heart muscle are difficult to observe and track, because the heart is a relatively smooth organ with few landmarks and non-rigid motion with a twisting motion or tangential component. The MRI tissue-tagging technique gives researchers the first glimpse into how the heart actually beats. This research uses the tagged MRI images of the heart to create a three dimensional model of a beating heart indicating the stress of a region. Tagged MRI techniques are still developing and vary vastly, meaning that there needs to be a methodology that can adapt to these changes rapidly and effectively, to meet the needs of the evolving technology. The focus of this research is to develop and test such a methodology by the means of a Strain Estimation Pipeline along with an effective way of validating any changes made to the individual processes that it comprises of

Modeling Left Ventricle Wall Motion Using Tagged Magnetic Resonance Imaging

A two-parameter computational model is proposed for the study of the regional motion of the left ventricle (LV) wall using tagged magnetic resonance imaging (tMRI) data. In this model, the LV wall motion is mathematically decomposed into two components, an isotropic deformation of the LV wall tissues along the short axis of LV and a non-uniform rotation of the tissues along the long axis of LV. The deformation and rotation parameters are determined by fitting the model to tMRI images of the short-axis planes of the LV wall. To validate this model, the tMRI images of the LV wall at the midventricular, apical and basal levels from eight subjects including healthy human, healthy and diabetic rats were studied. The result showed that this model is very effective in studying the LV wall motion and function in both small animals and human. With this model, the torsion, strain, and strain rate of the LV wall tissues can easily be calculated analytically at different phases of a cardiac cycle. It was found that the ratio of the torsion at endocardium to the torsion at epicardium is a constant during the cardiac motion even though the torsion varies with time significantly. The value of this constant of motion equals the ratio of the end diastolic radii of the LV wall at endocardium and epicardium and, therefore, is approximately the same for rats and human. This dissertation also includes a study of effects of exercise training on diabetic heart. In that study, global cardiac functions were measured using high field MRI and it was found that the global functions of diabetic heart could be improved by the training

Bridging spatiotemporal scales in biomechanical models for living tissues : from the contracting Esophagus to cardiac growth

Appropriate functioning of our body is determined by the mechanical behavior of our organs. An improved understanding of the biomechanical functioning of the soft tissues making up these organs is therefore crucial for the choice for, and development of, efficient clinical treatment strategies focused on patient-specific pathophysiology. This doctoral dissertation describes the passive and active biomechanical behavior of gastrointestinal and cardiovascular tissue, both in the short and long term, through computer models that bridge the cell, tissue and organ scale. Using histological characterization, mechanical testing and medical imaging techniques, virtual esophagus and heart models are developed that simulate the patient-specific biomechanical organ behavior as accurately as possible. In addition to the diagnostic value of these models, the developed modeling technology also allows us to predict the acute and chronic effect of various treatment techniques, through e.g. drugs, surgery and/or medical equipment. Consequently, this dissertation offers insights that will have an unmistakable impact on the personalized medicine of the future.Het correct functioneren van ons lichaam wordt bepaald door het mechanisch gedrag van onze organen. Een verbeterd inzicht in het biomechanisch functioneren van deze zachte weefsels is daarom van cruciale waarde voor de keuze voor, en ontwikkeling van, efficiënte klinische behandelingsstrategieën gefocust op de patiënt-specifieke pathofysiologie. Deze doctoraatsthesis brengt het passieve en actieve biomechanisch gedrag van gastro-intestinaal en cardiovasculair weefsel, zowel op korte als lange termijn, in kaart via computermodellen die een brug vormen tussen cel-, weefsel- en orgaanniveau. Aan de hand van histologische karakterisering, mechanische testen en medische beeldvormingstechnieken worden virtuele slokdarm- en hartmodellen ontwikkeld die het patiënt-specifieke orgaangedrag zo accuraat mogelijk simuleren. Naast de diagnostische waarde van deze modellen, laat de ontwikkelde modelleringstechnologie ook toe om het effect van verschillende behandelingstechnieken, via medicatie, chirurgie en/of medische apparatuur bijvoorbeeld, acuut en chronisch te voorspellen. Bijgevolg biedt deze doctoraatsthesis inzichten die een onmiskenbare impact zullen hebben op de gepersonaliseerde geneeskunde van de toekomst

Foetal echocardiographic segmentation

Congenital heart disease affects just under one percentage of all live births [1]. Those defects that manifest themselves as changes to the cardiac chamber volumes are the motivation for the research presented in this thesis. Blood volume measurements in vivo require delineation of the cardiac chambers and manual tracing of foetal cardiac chambers is very time consuming and operator dependent. This thesis presents a multi region based level set snake deformable model applied in both 2D and 3D which can automatically adapt to some extent towards ultrasound noise such as attenuation, speckle and partial occlusion artefacts. The algorithm presented is named Mumford Shah Sarti Collision Detection (MSSCD). The level set methods presented in this thesis have an optional shape prior term for constraining the segmentation by a template registered to the image in the presence of shadowing and heavy noise. When applied to real data in the absence of the template the MSSCD algorithm is initialised from seed primitives placed at the centre of each cardiac chamber. The voxel statistics inside the chamber is determined before evolution. The MSSCD stops at open boundaries between two chambers as the two approaching level set fronts meet. This has significance when determining volumes for all cardiac compartments since cardiac indices assume that each chamber is treated in isolation. Comparison of the segmentation results from the implemented snakes including a previous level set method in the foetal cardiac literature show that in both 2D and 3D on both real and synthetic data, the MSSCD formulation is better suited to these types of data. All the algorithms tested in this thesis are within 2mm error to manually traced segmentation of the foetal cardiac datasets. This corresponds to less than 10% of the length of a foetal heart. In addition to comparison with manual tracings all the amorphous deformable model segmentations in this thesis are validated using a physical phantom. The volume estimation of the phantom by the MSSCD segmentation is to within 13% of the physically determined volume

Flow Imaging Using MRI: Quantification and Analysis

A complex and challenging problem in flow study is to obtain quantitative flow information in opaque systems, for example, blood flow in biological systems and flow channels in chemical reactors. In this regard, MRI is superior to the conventional optical flow imaging or ultrasonic Doppler imaging. However, for high speed flows, complex flow behaviors and turbulences make it difficult to image and analyze the flows. In MR flow imaging, MR tagging technique has demonstrated its ability to simultaneously visualize motion in a sequence of images. Moreover, a quantification method, namely HARmonic Phase (HARP) analysis, can extract a dense velocity field from tagged MR image sequence with minimal manual intervention. In this work, we developed and validated two new MRI methods for quantification of very rapid flows. First, HARP was integrated with a fast MRI imaging method called SEA (Single Echo Acquisition) to image and analyze high velocity flows. Second, an improved HARP method was developed to deal with tag fading and data noise in the raw MRI data. Specifically, a regularization method that incorporates the law of flow dynamics in the HARP analysis was developed. Finally, the methods were validated using results from the computational fluid dynamics (CFD) and the conventional optimal flow imaging based on particle image velocimetry (PIV). The results demonstrated the improvement from the quantification using solely the conventional HARP method

Fluid-electro-mechanical model of the human heart for supercomputers

The heart is a complex system. From the transmembrane cell activity to the spatial organization in helicoidal fibers, it includes several spatial and temporal scales. The heart muscle is surrounded by two main tissues that modulate how it deforms: the pericardium and the blood. The former constrains the epicardial surface and the latter exerts a force in the endocardium. The main function of this peculiar muscle is to pump blood to the pulmonary and systemic circulations. In this way, solid dynamics of the heart is as important as the induced fluid dynamics. Despite the work done in computational research of multiphysics heart modelling, there is no reference of a tightly-coupled scheme that includes electrophysiology, solid and fluid mechanics in a whole human heart. In this work, we propose, develop and test a fluid-electro-mechanical model of the human heart. To start, the heartbeat phenomenon is disassembled in the different composing problems. The first building block is the electrical activity of the myocytes, that induces the mechanical deformation of the myocardium. The contraction of the muscle reduces the intracavitary space, that pushes out the contained blood. At the same time, the inertia, pressure and viscous stresses in this fluid exerts a force on the solid wall. In this way, we can understand the heart as a fluid-electro-mechanical problem. All the models are implemented in Alya, the Barcelona Supercomputing Center simulation software. A multi-code approach is used, splitting the problem in a solid and a fluid domain. In the former, electrophysiology coupled with solid mechanics are solved. In the later, fluid dynamics in an arbitrary Lagrangian-Eulerian domain are computed. The equations are spatially discretized using the finite element method and temporally discretized using finite differences. Facilitated by the multi-code approach, a novel high performance quasi-Newton method is developed to deal with the intrinsic issues of fluid-structure interaction problems in iomechanics. All the schemes are optimized to run in massively parallel computers. A wide range of experiments are shown to validate, test and tune the numerical model. The different hypothesis proposed — as the critical effect of the atrium or the presence of pericardium — are also tested in these experiments. Finally, a normal heartbeat is simulated and deeply analyzed. This healthy computational heart is first diseased with a left bundle branch block. After this, its function is restored simulating a cardiac resynchronization therapy. Then, a third grade atrioventricular block is simulated in the healthy heart. In this case, the pathologic model is treated with a minimally invasive leadless intracardiac pacemaker. This requires to include the device in the geometrical description of the problem, solve the structural problem with the tissue, and the fluid-structure interaction problem with the blood. As final experiment, we test the parallel performance of the coupled solver. In the cases mentioned above, the results are qualitatively compared against experimental measurements, when possible. Finally, a first glance in a coupled fluid-electro-mechanical cardiovascular system is shown. This model is build adding a one dimensional model of the arterial network created by the Laboratório Nacional de Computação Científica in Petropolis, Brasil. Despite the artificial geometries used, the outflow curves are comparable with physiological observations. The model presented in this thesis is a step towards the virtual human heart. In a near future computational models like the presented in this thesis will change how pathologies are understood and treated, and the way biomedical devices are designed.El corazón es un sistema complejo. Desde la actividad celular hasta la organización espacial en fibras helicoidales, incluye gran cantidad de escalas espaciales y temporales. El corazón está rodeado principalmente por dos tejidos que modulan su deformación: el pericardio y la sangre. El primero restringe el movimiento del epicardio, mientras el segundo ejerce fuerza sobre el endocardio. La función principal de este músculo es bombear sangre a la circulación sistémica y a la pulmonar. Así, la deformación del miocardio es tan importante como la fluidodinámica inducida. Al día de hoy, solo se han propuesto modelos parciales del corazón. Ninguno de los modelos publicados resuelve electrofisiología, mecánica del sólido, y dinámica de fluidos en una geometría completa del corazón. En esta tesis, proponemos, desarrollamos y probamos un modelo fluido -electro -mecánico del corazón. Primero, el problema del latido cardíaco es descompuesto en los distintos subproblemas. El primer bloque componente es la actividad eléctrica de los miocitos, que inducen la deformación mecánica del miocardio. La contratación de este músculo, reduce el espacio intracavitario, que empuja la sangre contenida. Al mismo tiempo, la inercia, presión y fuerzas viscosas del fluido inducen una presión sobre la pared del sólido. De esta manera, podemos entender el latido cardíaco como un problema fluido-electro-mecánico. Los modelos son implementados en Alya, el software de simulación del Barcelona Supercomputing Center. Se utiliza un diseño multi-código, separando el problema según el dominio en sólido y fluido. En el primero, se resuelve electrofisiología acoplado con mecánica del sólido. En el segundo, fluido dinámica en un dominio arbitrario Lagrangiano-Euleriano. Las ecuaciones son discretizadas espacial y temporalmente utilizando elementos finitos y diferencias finitas respectivamente. Facilitado por el diseño multi-codigo, se desarrolló un novedoso método quasi-Newton de alta performance, pensado específicamente para lidiar con los problemas intrínsecos de interacción fluido-estructura en biomecánica. Todos los esquemas fueron optimizados para correr en ordenadores masivamente paralelos.Se presenta un amplio espectro de experimentos con el fin de validar, probar y ajustar el modelo numérico. Las diferentes hipótesis propuestas tales como el efecto producido por la presencia de las aurículas o el pericardio son también demostradas en estos experimentos. Finalmente un latido normal es simulado y sus resultados son analizados con profundidad. El corazón computacional sano es, primeramente enfermado de un bloqueo de rama izquierda. Posteriormente se restaura la función normal mediante la terapia de resincronización cardíaca. Luego se afecta al corazón de un bloqueo atrioventricular de tercer grado. Esta patología es tratada mediante la implantación de un marcapasos intracardíaco. Para esto, se requiere incluir el dispositivo en la descripción geométrica, resolver el problema estructural con el tejido y la interacción fluido-estructura con la sangre. Como experimento numérico final, se prueba el desempeño paralelo del modelo acoplado.Finalmente, se muestran resultados preliminares para un modelo fluido-electro-mecánico del sistema cardiovascular. Este modelo se construye agregando un modelo unidimensional del árbol arterial. A pesar de las geometrías artificiales usadas, la curva de flujo en la raíz aórtica es comparable con observaciones experimentales. El modelo presentado aquí representa un avance hacia el humano virtual. En un futuro, modelos similares, cambiarán la forma en la que se entienden y tratan las enfermedades y la forma en la que los dispositivos biomédicos son diseñados.Postprint (published version

An image segmentation and registration approach to cardiac function analysis using MRI

Cardiovascular diseases (CVDs) are one of the major causes of death in the world. In recent years, significant progress has been made in the care and treatment of patients with such diseases. A crucial factor for this progress has been the development of magnetic resonance (MR) imaging which makes it possible to diagnose and assess the cardiovascular function of the patient. The ability to obtain high-resolution, cine volume images easily and safely has made it the preferred method for diagnosis of CVDs. MRI is also unique in its ability to introduce noninvasive markers directly into the tissue being imaged(MR tagging) during the image acquisition process. With the development of advanced MR imaging acquisition technologies, 3D MR imaging is more and more clinically feasible. This recent development has allowed new potentially 3D image analysis technologies to be deployed. However, quantitative analysis of cardiovascular system from the images remains a challenging topic. The work presented in this thesis describes the development of segmentation and motion analysis techniques for the study of the cardiac anatomy and function in cardiac magnetic resonance (CMR) images. The first main contribution of the thesis is the development of a fully automatic cardiac segmentation technique that integrates and combines a series of state-of-the-art techniques. The proposed segmentation technique is capable of generating an accurate 3D segmentation from multiple image sequences. The proposed segmentation technique is robust even in the presence of pathological changes, large anatomical shape variations and locally varying contrast in the images. Another main contribution of this thesis is the development of motion tracking techniques that can integrate motion information from different sources. For example, the radial motion of the myocardium can be tracked easily in untagged MR imaging since the epi- and endocardial surfaces are clearly visible. On the other hand, tagged MR imaging allows easy tracking of both longitudinal and circumferential motion. We propose a novel technique based on non-rigid image registration for the myocardial motion estimation using both untagged and 3D tagged MR images. The novel aspect of our technique is its simultaneous use of complementary information from both untagged and 3D tagged MR imaging. The similarity measure is spatially weighted to maximise the utility of information from both images. The thesis also proposes a sparse representation for free-form deformations (FFDs) using the principles of compressed sensing. The sparse free-form deformation (SFFD) model can capture fine local details such as motion discontinuities without sacrificing robustness. We demonstrate the capabilities of the proposed framework to accurately estimate smooth as well as discontinuous deformations in 2D and 3D CMR image sequences. Compared to the standard FFD approach, a significant increase in registration accuracy can be observed in datasets with discontinuous motion patterns. Both the segmentation and motion tracking techniques presented in this thesis have been applied to clinical studies. We focus on two important clinical applications that can be addressed by the techniques proposed in this thesis. The first clinical application aims at measuring longitudinal changes in cardiac morphology and function during the cardiac remodelling process. The second clinical application aims at selecting patients that positively respond to cardiac resynchronization therapy (CRT). The final chapter of this thesis summarises the main conclusions that can be drawn from the work presented here and also discusses possible avenues for future research