Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

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

Automated deep phenotyping of the cardiovascular system using magnetic resonance imaging

Across a lifetime, the cardiovascular system must adapt to a great range of demands from the body. The individual changes in the cardiovascular system that occur in response to loading conditions are influenced by genetic susceptibility, and the pattern and extent of these changes have prognostic value. Brachial blood pressure (BP) and left ventricular ejection fraction (LVEF) are important biomarkers that capture this response, and their measurements are made at high resolution. Relatively, clinical analysis is crude, and may result in lost information and the introduction of noise. Digital information storage enables efficient extraction of information from a dataset, and this strategy may provide more precise and deeper measures to breakdown current phenotypes into their component parts. The aim of this thesis was to develop automated analysis of cardiovascular magnetic resonance (CMR) imaging for more detailed phenotyping, and apply these techniques for new biological insights into the cardiovascular response to different loading conditions. I therefore tested the feasibility and clinical utility of computational approaches for image and waveform analysis, recruiting and acquiring additional patient cohorts where necessary, and then applied these approaches prospectively to participants before and after six-months of exercise training for a first-time marathon. First, a multi-centre, multi-vendor, multi-field strength, multi-disease CMR resource of 110 patients undergoing repeat imaging in a short time-frame was assembled. The resource was used to assess whether automated analysis of LV structure and function is feasible on real-world data, and if it can improve upon human precision. This showed that clinicians can be confident in detecting a 9% change in EF or a 20g change in LV mass. This will be difficult to improve by clinicians because the greatest source of human error was attributable to the observer rather than modifiable factors. Having understood these errors, a convolutional neural network was trained on separate multi-centre data for automated analysis and was successfully generalizable to the real-world CMR data. Precision was similar to human analysis, and performance was 186 times faster. This real-world benchmarking resource has been made freely available (thevolumesresource.com). Precise automated segmentations were then used as a platform to delve further into the LV phenotype. Global LVEFs measured from CMR imaging in 116 patients with severe aortic stenosis were broken down into ~10 million regional measurements of structure and function, represented by computational three-dimensional LV models for each individual. A cardiac atlas approach was used to compile, label, segment and represent these data. Models were compared with healthy matched controls, and co-registered with follow-up one year after aortic valve replacement (AVR). This showed that there is a tendency to asymmetric septal hypertrophy in all patients with severe aortic stenosis (AS), rather than a characteristic specific to predisposed patients. This response to AS was more unfavourable in males than females (associated with higher NT-proBNP, and lower blood pressure), but was more modifiable with AVR. This was not detected using conventional analysis. Because cardiac function is coupled with the vasculature, a novel integrated assessment of the cardiovascular system was developed. Wave intensity theory was used to combine central blood pressure and CMR aortic blood flow-velocity waveforms to represent the interaction of the heart with the vessels in terms of traveling energy waves. This was performed and then validated in 206 individuals (the largest cohort to date), demonstrating inefficient ventriculo-arterial coupling in female sex and healthy ageing. CMR imaging was performed in 236 individuals before training for a first-time marathon and 138 individuals were followed-up after marathon completion. After training, systolic/diastolic blood pressure reduced by 4/3mmHg, descending aortic stiffness decreased by 16%, and ventriculo-arterial coupling improved by 14%. LV mass increased slightly, with a tendency to more symmetrical hypertrophy. The reduction in aortic stiffness was equivalent to a 4-year reduction in estimated biological aortic age, and the benefit was greater in older, male, and slower individuals. In conclusion, this thesis demonstrates that automating analysis of clinical cardiovascular phenotypes is precise with significant time-saving. Complex data that is usually discarded can be used efficiently to identify new biology. Deeper phenotypes developed in this work inform risk reduction behaviour in healthy individuals, and demonstrably deliver a more sensitive marker of LV remodelling, potentially enhancing risk prediction in severe aortic stenosis

Mechanics of the tricuspid valve: from clinical diagnosis/treatment, in vivo and in vitro investigations, to patient-specific biomechanical modeling

Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states

In-vivo heterogeneous functional and residual strains in human aortic valve leaflets

Residual and physiological functional strains in soft tissues are known to play an important role in modulating organ stress distributions. Yet, no known comprehensive information on residual strains exist, or non-invasive techniques to quantify in-vivo deformations for the aortic valve (AV) leaflets. Herein we present a completely non-invasive approach for determining heterogeneous strains – both functional and residual – in semilunar valves and apply it to normal human AV leaflets. Transesophageal 3D echocardiographic (3DE) images of the AV were acquired from open-heart transplant patients, with each AV leaflet excised after heart explant and then imaged in a flattened configuration ex-vivo. Using an established spline parameterization of both 3DE segmentations and digitized ex-vivo images (Aggarwal et al., 2014), surface strains were calculated for deformation between the ex-vivo and three in-vivo configurations: fully open, just-coapted, and fully-loaded. Results indicated that leaflet area increased by an average of 20% from the ex-vivo to in-vivo open states, with a highly heterogeneous strain field. The increase in area from open to just-coapted state was the highest at an average of 25%, while that from just-coapted to fully-loaded remained almost unaltered. Going from the ex-vivo to in-vivo mid-systole configurations, the leaflet area near the basal attachment shrank slightly, whereas the free edge expanded by ~10%. This was accompanied by a 10° −20° shear along the circumferential-radial direction. Moreover, the principal stretches aligned approximately with the circumferential and radial directions for all cases, with the highest stretch being along the radial direction. Collectively, these results indicated that even though the AV did not support any measurable pressure gradient in the just-coapted state, the leaflets were significantly pre-strained with respect to the excised state. Furthermore, the collagen fibers of the leaflet were almost fully recruited in the just-coapted state, making the leaflet very stiff with marginal deformation under full pressure. Lastly, the deformation was always higher in the radial direction and lower along the circumferential one, the latter direction made stiffer by the preferential alignment of collagen fibers. These results provide significant insight into the distribution of residual strains and the in-vivo strains encountered during valve opening and closing in AV leaflets, and will form an important component of the tool that can evaluate valve׳s functional properties in a non-invasive manner

Automated Method for the Volumetric Evaluation of Myocardial Scar from Cardiac Magnetic Resonance Images

In most western countries cardiovascular diseases are the leading cause of death, and for the survivors of ischemic attack an accurate quantification of the extent of the damage is required to correctly assess its impact and for risk stratification, and to select the best treatment for the patient. Moreover, a fast and reliable tool for the assessment of the cardiac function and the measurement of clinical indexes is highly desirable. The aim of this thesis is to provide computational approaches to better detect and assess the presence of myocardial fibrosis in the heart, particularly but not only in the left ventricle, by performing a fusion of the information from different magnetic resonance imaging sequences. We also developed and provided a semiautomatic tool useful for the fast evaluation and quantification of clinical indexes derived from heart chambers volumes. The thesis is composed by five chapters. The first chapter introduces the most common cardiac diseases such as ischemic cardiomyopathy and describes in detail the cellular and structural remodelling phenomena stemming from heart failure. The second chapter regards the detection of the left ventricle through the development of a semi-automated approach for both endocardial and epicardial surfaces, and myocardial mask extraction. In the third chapter the workflow for scar assessment is presented, in which the previously described approach is used to obtain the 3D left ventricle patient-specific geometry; a registration algorithm is then used to superimpose the fibrosis information derived from the late gadolinium enhancement magnetic resonance imaging to obtain a patientspecific 3D map of fibrosis extension and location on the left ventricle myocardium. Focus of the fourth chapter is on the left atrium, and fibrotic tissue detection for gaining insight on atrial fibrillation. In the fifth chapter some conclusive remarks are presented with possible future developments of the presented work

Automated volume measurements in echocardiography by utilizing expert knowledge

Left ventricular (LV) volumes and ejection fraction (EF) are important parameters for diagnosis, prognosis, and treatment planning in patients with heart disease. These parameters are commonly measured by manual tracing in echocardiographic images, a procedure that is time consuming, prone to inter- and intra-observer variability, and require highly trained operators. This is particularly the case in three-dimensional (3D) echocardiography, where the increased amount of data makes manual tracing impractical. Automated methods for measuring LV volumes and EF can therefore improve efficiency and accuracy of echocardiographic examinations, giving better diagnosis at a lower cost. The main goal of this thesis was to improve the efficiency and quality of cardiac measurements. More specifically, the goal was to develop rapid and accurate methods that utilize expert knowledge for automated evaluation of cardiac function in echocardiography. The thesis presents several methods for automated volume and EF measurements in echocardiographic data. For two-dimensional (2D) echocardiography, an atlas based segmentation algorithm is presented in paper A. This method utilizes manually traced endocardial contours in a validated case database to control a snake optimized by dynamic programming. The challenge with this approach is to find the most optimal case in the database. More promising results are achieved in triplane echocardiography using a multiview and multi-frame extension to the active appearance model (AAM) framework, as demonstrated in paper B. The AAM generalizes better to new patient data and is based on more robust optimization schemes than the atlas-based method. In triplane images, the results of the AAM algorithm may be improved further by integrating a snake algorithm into the AAM framework and by constraining the AAM to manually defined landmarks, and this is shown in paper C. For 3D echocardiograms, a clinical semi-automated volume measurement tool with expert selected points is validated in paper D. This tool compares favorably to a reference measurement tool, with good agreement in measured volumes, and with a significantly lower analysis time. Finally, in paper E, fully automated real-time segmentation in 3D echocardiography is demonstrated using a 3D active shape model (ASM) of the left ventricle in a Kalman filter framework. The main advantage of this approach is its processing performance, allowing for real-time volume and EF estimates. Statistical models such as AAMs and ASMs provide elegant frameworks for incorporating expert knowledge into segmentation algorithms. Expert knowledge can also be utilized directly through manual input to semi-automated methods, allowing for manual initialization and correction of automatically determined volumes. The latter technique is particularly suitable for clinical routine examinations, while the fully automated 3D ASM method can extend the use of echocardiography to new clinical areas such as automated patient monitoring. In this thesis, different methods for utilizing expert knowledge in automated segmentation algorithms for echocardiography have been developed and evaluated. Particularly in 3D echocardiography, these contributions are expected to improve efficiency and quality of cardiac measurements