A New Methodology for Multiscale Myocardial Deformation and Strain Analysis Based on Tagging MRI

Myocardial deformation and strain can be investigated using suitably encoded cine MRI that admits disambiguation of material motion. Practical limitations currently restrict the analysis to in-plane motion in cross-sections of the heart (2D + time), but the proposed method readily generalizes to 3D + time. We propose a new, promising methodology, which departs from a multiscale algorithm that exploits local scale selection so as to obtain a robust estimate for the velocity gradient tensor field. Time evolution of the deformation tensor is governed by a first-order ordinary differential equation, which is completely determined by this velocity gradient tensor field. We solve this matrix-ODE analytically and present results obtained from healthy volunteers as well as from patient data. The proposed method requires only off-the-shelf algorithms and is readily applicable to planar or volumetric tagging MRI sampled on arbitrary coordinate grids

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

Background: Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure. Methods: MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10). Results: Mice subjected to a mild constriction showed increased LV mass (P0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05). Conclusions: Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence

Computer-aided detection of wall motion abnormalities in cardiac MRI

With the increasing prevalence and hospitalization rate of ischaemic heart disease, an explosive growth of diagnostic imaging for ischaemia is ongoing. Clinical decision making on revascularization procedures requires reliable viability assessment to assure long-term patient survival and to elevate cost effectiveness of the therapy and treatment. As such, the demand is increasing for a computer-assisted diagnosis (CAD) method for ischaemic heart disease that supports clinicians with an objective analysis of infarct severity, a viability assessment or a prediction of potential functional improvement before performing revascularization. The goal of this thesis was to explore novel mechanisms that can be used for CAD in ischaemic heart disease, particularly through wall motion analysis from cardiac MR images. Existing diagnostic treatment of wall motion analysis from cardiac MR relies on visual wall motion scoring, which suffers from inter- and intra-observer variability. To minimize this variability, the automated method must contain essential knowledge on how the heart contracts normally. This enables automatic quantification of regional abnormal wall motion, detection of segments with contractile reserve and prediction of functional improvement in stress.1. Bontius Stichting inz. Doelfonds beeldverwerking, 2. Foundation Imago, 3. ASCI research school, and 4. Library of the University of Leiden.UBL - phd migration 201

Feature based estimation of myocardial motion from tagged MR images

In the past few years we witnessed an increase in mortality due to cancer relative to mortality due to cardiovascular diseases. In 2008, the Netherlands Statistics Agency reports that 33.900 people died of cancer against 33.100 deaths due to cardiovascular diseases, making cancer the number one cause of death in the Netherlands [33]. Even if the rate of people affected by heart diseases is continually rising, they "simply don’t die of it", according to the research director Prof. Mat Daemen of research institute CARIM of the University of Maastricht [50]. The reason for this is the early diagnosis, and the treatment of people with identified risk factors for diseases like ischemic heart disease, hypertrophic cardiomyopathy, thoracic aortic disease, pericardial (sac around the heart) disease, cardiac tumors, pulmonary artery disease, valvular disease, and congenital heart disease before and after surgical repair. Cardiac imaging plays a crucial role in the early diagnosis, since it allows the accurate investigation of a large amount of imaging data in a small amount of time. Moreover, cardiac imaging reduces costs of inpatient care, as has been shown in recent studies [77]. With this in mind, in this work we have provided several tools with the aim to help the investigation of the cardiac motion. In chapters 2 and 3 we have explored a novel variational optic flow methodology based on multi-scale feature points to extract cardiac motion from tagged MR images. Compared to constant brightness methods, this new approach exhibits several advantages. Although the intensity of critical points is also influenced by fading, critical points do retain their characteristic even in the presence of intensity changes, such as in MR imaging. In an experiment in section 5.4 we have applied this optic flow approach directly on tagged MR images. A visual inspection confirmed that the extracted motion fields realistically depicted the cardiac wall motion. The method exploits also the advantages from the multiscale framework. Because sparse velocity formulas 2.9, 3.7, 6.21, and 7.5 provide a number of equations equal to the number of unknowns, the method does not suffer from the aperture problem in retrieving velocities associated to the critical points. In chapters 2 and 3 we have moreover introduced a smoothness component of the optic flow equation described by means of covariant derivatives. This is a novelty in the optic flow literature. Many variational optic flow methods present a smoothness component that penalizes for changes from global assumptions such as isotropic or anisotropic smoothness. In the smoothness term proposed deviations from a predefined motion model are penalized. Moreover, the proposed optic flow equation has been decomposed in rotation-free and divergence-free components. This decomposition allows independent tuning of the two components during the vector field reconstruction. The experiments and the Table of errors provided in 3.8 showed that the combination of the smoothness term, influenced by a predefined motion model, and the Helmholtz decomposition in the optic flow equation reduces the average angular error substantially (20%-25%) with respect to a similar technique that employs only standard derivatives in the smoothness term. In section 5.3 we extracted the motion field of a phantom of which we know the ground truth of and compared the performance of this optic flow method with the performance of other optic flow methods well known in the literature, such as the Horn and Schunck [76] approach, the Lucas and Kanade [111] technique and the tuple image multi-scale optic flow constraint equation of Van Assen et al. [163]. Tests showed that the proposed optic flow methodology provides the smallest average angular error (AAE = 3.84 degrees) and L2 norm = 0.1. In this work we employed the Helmholtz decomposition also to study the cardiac behavior, since the vector field decomposition allows to investigate cardiac contraction and cardiac rotation independently. In chapter 4 we carried out an analysis of cardiac motion of ten volunteers and one patient where we estimated the kinetic energy for the different components. This decomposition is useful since it allows to visualize and quantify the contributions of each single vector field component to the heart beat. Local measurements of the kinetic energy have also been used to detect areas of the cardiac walls with little movement. Experiments on a patient and a comparison between a late enhancement cardiac image and an illustration of the cardiac kinetic energy on a bull’s eye plot illustrated that a correspondence between an infarcted area and an area with very small kinetic energy exists. With the aim to extend in the future the proposed optic flow equation to a 3D approach, in chapter 6 we investigated the 3D winding number approach as a tool to locate critical points in volume images. We simplified the mathematics involved with respect to a previous work [150] and we provided several examples and applications such as cardiac motion estimation from 3-dimensional tagged images, follicle and neuronal cell counting. Finally in chapter 7 we continued our investigation on volume tagged MR images, by retrieving the cardiac motion field using a 3-dimensional and simple version of the proposed optic flow equation based on standard derivatives. We showed that the retrieved motion fields display the contracting and rotating behavior of the cardiac muscle. We moreover extracted the through-plane component, which provides a realistic illustration of the vector field and is missed by 2-dimensional approaches

Analysis of the myocardial function using tagging MR

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)Heart diseases can often manifest themselves by irregularities in the movement of the heart muscle. To assess the function of the myocardium, a method based in the Optic Flow Constrain Equation (OFCE) is applied in tagging MR images. The sequence of tagging MR images allows us to detect deviations in deformation and strain through time. However, the application of the OFCE implies the assumption of spatial phase conservation. Therefore, harmonic filters in the Fourier domain were used in each frame of the sequence to remove the variation of intensity trough time. In order to achieve a model capable of distinguishing a malfunction from normal function of the cardiac wall it is necessary to acknowledge what is the ground truth and which factors can affect the results. This study explores several scenarios using synthetic data that mimic tagged MR images in order to discover which variables can optimize the OFCE. This work allows us to analyze up to what extension the OFCE can be applied to a cardiac motion simulator (CMS) based on Waks et al. [1], capable of reproducing the normal function of the heart. After a series of tests with simulated data and the respective comparison with real volunteers data, it is possible to assess quantitatively the method used.Grande parte das doenças cardíacas estão associadas a um consequente mau funcionamento dos músculos cardíacos. Sendo que o músculo cardíaco maior e do qual depende o funcionamento do coração é o miocárdio, torna-se relevante quantificar a deformação do mesmo. Esta quantificação permite calcular o volume do sangue que é bombeado por ciclo cardiaco e a fracção de ejecção cardíaca. Neste trabalho propoem-se a aplicação de um método que utiliza a "Optic Flow Constrain Equation"(OFCE), a imagens de ressonância magnética (RM) marcadas. A sequencia de imagens the RM marcadas permite-nos detectar desvios na deformação e tensão no tempo. No entanto, o uso da OFCE implica que se assuma a existência de conservação de fase. Para tal, para remover a variação de intensidade no tempo, foram aplicados filtros no domínio de Fourier a cada uma das imagens da sequência. Para atingir um modelo capaz de distinguir um funcionamento anormal do miocárdio é necessário saber o que significa numéricamente o comportamento normal de um músculo saudável e quais os factores que podem afectar a sua quantificação. Este estudo baseia-se na simulação de cenários para determinar que variáveis podem ajudar a optimização do método com OFCE. Este trabalho permite analizar a aplicabilidade da OFCE a um simulador de movimento cardíaco (SMC), baseado no trabalho deWaks et al. [1], capaz de reproduzir o movimento normal do coração. Depois do estudo intensivo das várias simulações e respectiva comparação com dados reais, é possível avaliar quantitativamente o método utilizado

On motion in dynamic magnetic resonance imaging: Applications in cardiac function and abdominal diffusion

La imagen por resonancia magnética (MRI), hoy en día, representa una potente herramienta para el diagnóstico clínico debido a su flexibilidad y sensibilidad a un amplio rango de propiedades del tejido. Sus principales ventajas son su sobresaliente versatilidad y su capacidad para proporcionar alto contraste entre tejidos blandos. Gracias a esa versatilidad, la MRI se puede emplear para observar diferentes fenómenos físicos dentro del cuerpo humano combinando distintos tipos de pulsos dentro de la secuencia. Esto ha permitido crear distintas modalidades con múltiples aplicaciones tanto biológicas como clínicas. La adquisición de MR es, sin embargo, un proceso lento, lo que conlleva una solución de compromiso entre resolución y tiempo de adquisición (Lima da Cruz, 2016; Royuela-del Val, 2017). Debido a esto, la presencia de movimiento fisiológico durante la adquisición puede conllevar una grave degradación de la calidad de imagen, así como un incremento del tiempo de adquisición, aumentando así tambien la incomodidad del paciente. Esta limitación práctica representa un gran obstáculo para la viabilidad clínica de la MRI. En esta Tesis Doctoral se abordan dos problemas de interés en el campo de la MRI en los que el movimiento fisiológico tiene un papel protagonista. Éstos son, por un lado, la estimación robusta de parámetros de rotación y esfuerzo miocárdico a partir de imágenes de MR-Tagging dinámica para el diagnóstico y clasificación de cardiomiopatías y, por otro, la reconstrucción de mapas del coeficiente de difusión aparente (ADC) a alta resolución y con alta relación señal a ruido (SNR) a partir de adquisiciones de imagen ponderada en difusión (DWI) multiparamétrica en el hígado.Departamento de Teoría de la Señal y Comunicaciones e Ingeniería TelemáticaDoctorado en Tecnologías de la Información y las Telecomunicacione

Analysis of strain in the human left ventricle using real-time 3D echocardiography and optical flow

Cardiovascular disease (CVD) consistently ranks among the leading causes of death in the United States. The most common subtype of CVD, ischemic heart disease, is a frequent precursor of myocardial infarction and heart failure, most commonly affecting the left ventricle (LV). Today, echocardiography is regarded as the gold standard in screening, diagnosis, and monitoring of LV dysfunction. But while global assessment of LV function tends to be quantitative, cardiologists with specific expertise still perform many regional evaluations subjectively. However, a more objective and quantitative measure of regional function – myocardial strain – has been developed and widely studied using 2D echocardiography. With recent developments in real-time 3D echocardiography (RT3DE), it has become possible to measure strain in its native 3D orientation as well. Our laboratory’s earlier work introduced the Optical Flow (OF) method of strain analysis, which was validated on simulated echocardiograms as well as through animal studies. The principal goal of this thesis is to translate this OF-based method of strain estimation from the research setting to the patient’s bedside. We have performed a series of studies to evaluate the feasibility, accuracy, and reproducibility of OF-based myocardial strain estimation in a routine clinical setting. The first investigation focused on the optimization of RT3DE acquisition and the OF processing pipeline for use in human subjects. Subsequently, we evaluated the capacity of this technique to distinguish abnormal strain patterns in patients with CVD and varying degrees of LV dysfunction. Our analysis revealed that segmental strain measures obtained by OF may have better sensitivity and specificity than the more commonly used global LV strains. Our third validation study examined the reproducibility of these strain measures in both healthy and diseased populations. We established that OF-based strain measures demonstrate repeatability comparable to that achieved by the latest commercial software commonly used in clinical research to estimate 2D or 3D strain. These studies were driven in large part by the absence of a ground truth or accepted gold standard of 3D strain measurements in the human LV. However, cardiac magnetic resonance imaging has had considerable success in measuring some forms of strain in the human LV. We therefore began to develop an image-processing pipeline to derive strain estimates from a new pulse sequence called 3D-DENSE. We further sought to improve the OF pipeline by automating the process of tracking the LV border. To this end, we developed a level-set based technique which tracks the LV endocardium. Our evaluation of its performance on RT3DE data confirmed that this method performs within the limits of inter-observer variability. Overall, our pilot studies of OF-based strain estimation demonstrate that the technique possesses several promising features for improving cardiologists’ ability to quantify and interpret the complex three-dimensional deformations of the human LV

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

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload