Thesis Abstract

            ABSTRACT 

There is a large need for accurate methods detecting cardiovascular diseases, since they are one of the leading causes of mortality in the world, accounting for 29.3% of all deaths. Due to the complexity of the cardiovascular system, it is very challenging to develop methods for quantification of its function in order to diagnose, prevent and treat cardiovascular diseases. Ultrasound is a technique allowing for inexpensive, noninvasive imaging, but requires an experienced echocardiographer. Nowadays, methods like Tissue Doppler imaging (TDI) and Speckle tracking imaging (STI), measuring motion and deformation in the myocardium and the vessel walls, are getting more common in routine clinical practice, but without a proper visualization of the data provided by these methods, they are time-consuming and difficult to interpret. Thus, the general aim of this thesis was to develop novel ultrasound-based methods for accurate quantification and easily interpretable visualization of cardiovascular function. Five methods based on TDI and STI were developed in the present studies. The first study comprised development of a method for generation of bull’s-eye plots providing a color-coded two-dimensional visualization of myocardial longitudinal velocities. The second study proposed the state diagram of the heart as a new circular visualization tool for cardiac mechanics, including segmental color-coding of cardiac time intervals. The third study included development of a method describing the rotation pattern of the left ventricle by calculating rotation axes at different levels of the left ventricle throughout the cardiac cycle. In the fourth study, deformation data from the artery wall were tested as input to wave intensity analysis providing information of the ventricular – arterial interaction. The fifth study included an in-silico feasibility study to test the assessment of both radial and longitudinal strain in a kinematic model of the carotid artery. The studies showed promising results indicating that the methods have potential for the detection of different cardiovascular diseases and are feasible for use in the clinical setting. However, further development of the methods and both quantitative comparison of user dependency, accuracy and ease of use with other established methods evaluating cardiovascular function, as well as additional testing of the clinical potential in larger study populations, are needed. 

Keywords Ultrasound, Tissue Doppler imaging, Speckle tracking imaging, cardiovascular function, visualization, quantification

Thesis Overview

1.0 INTRODUCTION 

I wish to start this thesis referring to a photo of the white-board in our conference room (Figure 1.1). The illustration in the photo, which is taken after one of several long and intensive discussions about cardiovascular mechanics, looks chaotic and very complex. I believe I can with certainty claim that this is not only the case for our discussions, but also for the understanding of cardiovascular mechanics in general. The cardiovascular system is complex. This complexity has frequently been addressed in the literature and depends foremost on multiple regulatory mechanisms and both linear and nonlinear relationships among a large number of cardiovascular variables [1]. There is a considerable amount of publications in this field and cardiac mechanics and the pumping function of the heart have been differently described over the years. However, the function of this substantial organ, which averagely has to perform over 100.000 heartbeats every day and in total pump more than 400 million liters of blood during a lifetime without any rest, is still not fully understood [2]. Since cardiovascular disease is one of the leading causes of mortality in the world, accounting for 29.3% of all deaths [3], there is a large need for quantitative and accurate methods for the early detection of cardiovascular diseases. 

In developed countries, ischemic heart disease and cerebrovascular disease are together responsible for 36% of all deaths [4]. Moreover, the mortality and burden resulting from cardiovascular diseases are rapidly increasing in developing regions and population growth, ageing and globalized lifestyle changes combine to make cardiovascular disease an increasingly important cause of morbidity and mortality [5]. Due to the complexity of the cardiovascular system, it is very challenging to develop methods for quantification of its function in order to diagnose, prevent and treat cardiovascular diseases. Ultrasound is a technique allowing for inexpensive, noninvasive imaging of the heart and the vessels. The technique was applied to cardiac applications for the first time in 1954 by Edler and Hertz [6], and has during recent years, grown in importance within cardiovascular imaging. 

Traditionally, a diagnosis was obtained by the visual interpretation of gray-scale sequences. Nowadays, methods like Tissue Doppler imaging (TDI) and Speckle tracking imaging (STI), measuring motion and deformation in the myocardium and the vessel walls, are getting more common in routine clinical practice. This leads to a decreased user dependency but gives us a large set of parameters that are difficult to overview. First, the most important data have to be extracted from the large number of different signals, and then they must be visualized in an easily interpretable way. 

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1.1 Thesis outlook

The thesis is organized into 13 chapters followed by the five included papers, on which this thesis is based on. After this short introduction, the aims are stated. Thereafter, the list of included papers is presented. The cardiovascular system and the techniques that have been used during this thesis work are described in Chapters 4 and 5. Chapter 6 provides a literature review of methods to evaluate cardiovascular function. The following two chapters, Chapters 7 and 8, present used methodologies and research contributions within this thesis work. The results from the studies are discussed in Chapter 9 and the conclusions are presented in Chapter 10. Finally, future work, other scientific contributions by the author and references are presented.

The general aim of this thesis was to develop novel ultrasound-based methods for accurate quantification and easily interpretable visualization of cardiovascular function. In particular, the methods aimed to be feasible in the clinical setting with the possible potential for early detection of cardiovascular disease. The specific aims are listed below for each of the studies: 

• To develop and test a method in the clinical setting, that through the stepwise colorcoded bull’s-eye plot, allows for a quick and easily comprehensible visual analysis of the left ventricular (LV) longitudinal contraction pattern in a single image (Study I). 

• To test the feasibility of a method, visualizing cardiac mechanics through cardiac phases, by performing a clinical study including a comparison with established echocardiography methods, and by providing clinical examples demonstrating its potential use in the clinical setting (Study II). 

• To develop an ultrasound-based method to calculate the rotation axis of the LV in a three-dimensional (3D) aspect throughout the cardiac cycle and to apply it in a group of healthy individuals (Study III). • To test if deformation data assessed in the vessel wall can be used as input to a method studying the ventricular-arterial interaction through wave intensity (WI) analysis (Study IV). 

• To test the feasibility of simultaneous assessment of radial and longitudinal strain in the carotid artery with commercially available hardware using computer simulations (Study V).