Dynamic Views of Structure and Function during Heart Morphogenesis

Congenital heart defects remain the most common birth defect in humans, occurring in over 1% of live births. The high prevalence of cardiac malformations can be partially attributed to limited knowledge regarding the embryonic roots of the disease. A variety of congenital heart defects are thought to arise from combinations of genetic and epigenetic factors. In an effort to better understand this dynamic relationship, our study explores the structure and function of the developing heart and valves and examines hemodynamic factors influencing valvulogenesis. In order to study cardiac mechanics, we employed novel high-speed confocal microscopy and four-dimensional visualization techniques. A dynamic four-dimensional dataset describing heart and valve development along with blood flow patterns throughout cardiac morphogenesis is presented. Utilizing newly developed tools, we propose a novel pumping mechanism in the valveless embryonic heart tube via elastic wave propagation and reflection. We show that this form of pumping leads to oscillatory shear stresses in the developing atrio-ventricular canal, a phenomenon that had not previously been documented. An in vivo method to modulate trans-valvular oscillatory flows is described and used to test our hypothesis that oscillatory shear stress across the primitive valve cushions stimulates heart valve leaflet formation. Our results suggest hemodynamic forces contribute to valvulogenesis and enhance our understanding of normal and abnormal heart valve development

Adverse effect left congenital diaphragmatic hernia to position and function of the fetal heart

Background: There many heart problems in patients with CDH.Methods: Between January 2012 and July 2015, three pregnancies (1:2153) performed ultrasound examination to investigate suspected CDH. All symptoms displayed descriptively in table.Results: In prenatal life, ultrasonography has a high sensitivity for detection of congenital diaphragmatic hernia. The definite ultrasonographic diagnosis of fetal congenital diaphragmatic hernia lies on the visualization of abdominal organs in the chest. The ultrasonographic hallmark of this condition is a fluid-filled mass in same level with fetal heart. Ultrasonographic features indicative of congenital diaphragmatic hernia include polyhydramnios; an absent or intraabdominal stomach bubble, mediastinal-cardiac shift away from the side of the herniation and a small fetal abdominal circumference or growth retarded. The effect of stomach pressure results 100% the position of the heart and affect the effectiveness of the heart such as pressure on the heart resulting tamponade effect.Conclusions: Cardiac changes due to the insistence by CDH can lead to changes position, anatomical and cardiac function

Uncertainty visualization in forward and inverse cardiac models

pre-printQuantification and visualization of uncertainty in cardiac forward and inverse problems with complex geometries is subject to various challenges. Specific to visualization is the observation that occlusion and clutter obscure important regions of interest, making visual assessment difficult. In order to overcome these limitations in uncertainty visualization, we have developed and implemented a collection of novel approaches. To highlight the utility of these techniques, we evaluated the uncertainty associated with two examples of modeling myocardial activity. In one case we studied cardiac potentials during the repolarization phase as a function of variability in tissue conductivities of the ischemic heart (forward case). In a second case, we evaluated uncertainty in reconstructed activation times on the epicardium resulting from variation in the control parameter of Tikhonov regularization (inverse case). To overcome difficulties associated with uncertainty visualization, we implemented linked-view windows and interactive animation to the two respective cases. Through dimensionality reduction and superimposed mean and standard deviation measures over time, we were able to display key features in large ensembles of data and highlight regions of interest where larger uncertainties exist

Heart frontal section and hypertrophic cardiomyopathy

The heart is one of the most vital and complex organs in the body. However, most of the existing heart animations focus on showing the outer surface of a beating heart, and attempt to simulate its function with its outer views. This thesis model, however, focuses on the inner structure of the heart in order to provide detailed visualizations of different parts of the heart, their functions and the related disease. This thesis model has been created by using a real human heart provided by the Rochester Institute of Technology, as well as published material about the inside structure of the heart. The model of the frontal section of the heart was made by using the 3D computer graphic software known as Maya as well as 2D graphics using Adobe Flash. This project includes the visual simulation of a heart disease known as Hypertrophic Cardiomyopathy. This is a heart disease that develops from abnormal growth of interventricular septum. This enlarged septum impedes blood flow. If this disease is not treated, the patient can suddenly go into cardiac arrest. This 3D model of heart frontal section is created to provide detailed visualization of the cause, process and surgical treatments of Hypertrophic Cardiomyopathy

Spire, an Actin Nucleation Factor, Regulates Cell Division during Drosophila Heart Development

The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir), an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin)-, Even-skipped- and Seven up (Svp)-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate. Furthermore, through visualization of double heterozygous embryos, we determines that spir cooperates with CycA for heart cell specification and division. Finally, when comparing the spir mutant phenotype with that of a CycA mutant, the results suggest that most Svp-positive progenitors in spir mutant embryos cannot undergo full cell division at cell cycle 15, and that Tin-positive progenitors are arrested at cell cycle 16 as double-nucleated cells. We conclude that Spir plays a crucial role in controlling dorsal vessel formation and has a function in cell division during heart tube morphogenesis

State diagrams of the heart – a new approach to describing cardiac mechanics

<p>Abstract</p> <p>Background</p> <p>Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements.</p> <p>Methods</p> <p>We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter- and intraventricular function of the heart by displaying the cardiac phases.</p> <p>Results</p> <p>The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods.</p> <p>Conclusion</p> <p>The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.</p

The Heart of a Horse: 3‐D Echocardiographic Analysis of the Equine Aortic Valve

Aortic regurgitation (AR) can be a normal function of aging or a disease in younger horses. Symptoms range from no outward signs to decreased performance to sudden cardiac arrest. My study used 3‐D echocardiography, ultrasound of the heart, to look at the equine aortic valve and assess it for AR severity. Three‐dimensional echocardiography records a pyramid of tissue rather than a 2‐D plane, showing cardiac structures difficult to visualize in standard 2‐D methods. In normal valves, only the edges of the cusps were visible, as the tissue is very thin when images were taken from the right, which is standard positioning for imaging the aortic valve. I observed the cusps of the aortic valve to be thickened in horses with AR, with degree of thickening corresponding to AR severity. Left‐sided images were generally worse quality than right‐sided, but in some cases there was better visualization of some aspects of the aortic valve in left‐sided images. 3‐D echocardiography potentially could be used as a standard for diagnosis of AR, specifically by looking at cusp thicknesses, and could more specifically diagnose which part of the valve is affected by disease

Doctor of Philosophy

dissertationIn this dissertation, we advance the theory and practice of verifying visualization algorithms. We present techniques to assess visualization correctness through testing of important mathematical properties. Where applicable, these techniques allow us to distinguish whether anomalies in visualization features can be attributed to the underlying physical process or to artifacts from the implementation under verification. Such scientific scrutiny is at the heart of verifiable visualization - subjecting visualization algorithms to the same verification process that is used in other components of the scientific pipeline. The contributions of this dissertation are manifold. We derive the mathematical framework for the expected behavior of several visualization algorithms, and compare them to experimentally observed results in the selected codes. In the Computational Science & Engineering community CS&E, this technique is know as the Method of Manufactured Solution (MMS). We apply MMS to the verification of geometrical and topological properties of isosurface extraction algorithms, and direct volume rendering. We derive the convergence of geometrical properties of isosurface extraction techniques, such as function value and normals. For the verification of topological properties, we use stratified Morse theory and digital topology to design algorithms that verify topological invariants. In the case of volume rendering algorithms, we provide the expected discretization errors for three different error sources. The results of applying the MMS is another important contribution of this dissertation. We report unexpected behavior for almost all implementations tested. In some cases, we were able to find and fix bugs that prevented the correctness of the visualization algorithm. In particular, we address an almost 2 0 -year-old bug with the core disambiguation procedure of Marching Cubes 33, one of the first algorithms intended to preserve the topology of the trilinear interpolant. Finally, an important by-product of this work is a range of responses practitioners can expect to encounter with the visualization technique under verification