1.3 Organization of the Manuscript
This manuscript is structured in five parts:
• Part I provides and introduction by describing the motivation and main objectives of the present thesis (Chapter 1), the background related to the physiology and the state of the art of CO monitoring devices (Chapter 2), as well as the technical aspects of EIT (Chapter 3);
• Part II first presents the creation of a bioimpedance model of a human thorax (Chapter 4), which is used in simulations to investigate the origins of cardiac EIT signals (Chapter 5), and to study the feasibility and limitations of EIT-based SV estimation (Chapter 6); • Part III describes two clinical studies by first giving a rationale for performing measure-
ments on patients (Chapter 7), followed by presenting the two studies, one performed in the operating room (Chapter 8), and the other in the intensive care unit (Chapter 9); • Part IV starts by describing the limitations of currently available clinical EIT devices and suggesting an improved setup (Chapter 10), followed by presenting a novel approach allowing to fairly compare EIT image reconstructions from different setups (Chapter 11). Finally, the testing of the improved measurement setup in an experimental study on healthy volunteers is presented (Chapter 12);
• Part V concludes this thesis by providing a synthesis and suggestions for future work (Chapter 13).
In addition, the appendices in Part VI contain: A simulation-based study to investigate the feasibility of aortic blood pressure measurement via EIT (Appendix A); The mathematical aspects of ensemble averaging and the related signal quality estimator (Appendix B); Additi- onal figures of the clinical study in the operating room (Appendix C); Additional figures of the clinical study in the intensive care unit (Appendix D); Additional figures and tables of the experimental study on healthy volunteers (Appendix E).
2
Stroke Volume and Cardiac Output
In this chapter we first give a brief introduction into cardiovascular physiology with parti- cular focus on stroke volume (SV) and cardiac output (CO). Then we present the different technologies currently available for the measurement of CO ranging from the highly invasive gold standard reference to noninvasive approaches. After mentioning some aspects to be considered when comparing CO measurements of different devices, we list the requirements for an ideal CO monitoring device and the reasons why EIT might be an appropriate candidate.
2.1 Cardiovascular Physiology in a Nutshell
In the following, we give a brief background to cardiovascular physiology necessary to un- derstand the basic mechanisms related to SV and CO. The reader interested in more detail is referred to the books by Levick [92], Nichols et al. [107] or Westerhof et al. [159].
2.1.1 Cardiovascular System and Hemodynamic Parameters
The cardiovascular system comprises the heart, the blood and the blood vessels. Its main function is the transport of substances (including oxygen, water and nutrients) to the tissues and the washout of metabolic waste products (including carbon dioxide) from these tissues. Other functions are the distribution of hormones and the regulation of body temperature [92]. The central organ of the cardiovascular system is the heart. As shown in Figure 2.1a, it is a hollow organ consisting of specialized muscular tissue forming four chambers (two atria and two ventricles) and containing four valves (two inlet and two outlet valves) which enable an unidirectional blood flow. From an engineer’s perspective, the heart represents two synchro- nized pumps (each with one atrium, one ventricle and two valves) connected in series via the blood vessels to one circulatory system, as illustrated in Figure 2.1b. The right part of the heart – the first pump – supplies the lungs with deoxygenated blood (black) returning from the systemic circulation, whereas the left part – the second pump – collects oxygenated blood (red) from the lungs and distributes it among the different organs in the systemic circulation.
(a) (b)
Figure 2.1 – (a) Structure of the heart: pink/gray indicating oxygenated/deoxygenated blood, respectively. AoV/PuV stands for aortic/pulmonary valve. (b) Illustration of the cardiovascular system which can be separated into pulmonary and systemic circulation. The first carries deoxygenated blood (black) from the right ventricle (RV) to the lungs and returns oxygenated blood (red) to the left atrium (LA). The latter feeds all systemic organs with oxygenated blood from the left ventricle (LV) and returns deoxygenated blood back to the right atrium (RA). The figure (a) is from Fig. 1.4 in [92] and (b) from Fig. 1.5 in [92], both © 2010 JR Levick.
The performance, and thus the health of the cardiovascular system, can be assessed via so- called hemodynamic parameters. One such parameter already introduced in the previous chapter is the CO, i.e. the amount of blood volume pumped by the heart through the circulation in one minute. CO is the product of heart rate (HR) and stroke volume (SV): CO=HR·SV. SV is the amount of blood ejected per contraction by one ventricle during the cardiac phase called
systole. In contrast, during the second phase calleddiastole, the ventricles relax and are being refilled partly due to atrial contraction. As a result of this alternation between diastole and systole the blood pressure in the arteries is pulsatile, i.e. typical systemic pressure values vary from a minimum (diastolic value) of 80 mmHg to a maximum (systolic value) of 120 mmHg [92]. The gradient of mean blood pressure (∆P) between the aorta (PAO) and the vena cava
(PVC) is the driving force for blood flow through the systemic circulation:
CO=Q˙=∆P
RT =
PAO−PVC
RT
, (2.1)
2.1. Cardiovascular Physiology in a Nutshell
Factors Affecting Heart Rate Factors Affecting Stroke Volume
Cardiac Output (CO) = HR ⋅ SV
Heart Rate (HR) Stroke Volume (SV) = EDV - ESV Afterload Contractility
End Systolic Volume (ESV) End Diastolic Volume (EDV) Sympathetic and Parasympathetic Activity Hormones Preload
Figure 2.2 – Main factors affecting heart rate and stroke volume and thus cardiac output. Adapted and simplified from [16, Figure 19.35].
PAOis in the range of 100 mmHg,PVCis close to zero. Thus, the total vascular resistance of the
systemic circulation is in the order ofRT ≈20 mmHg·min/L (=100 mmHg/(5 L/min)) [92]. In
contrast, the total vascular resistance of the pulmonary circulation is much smaller because pulmonary blood vessels are much shorter and wider. This explains why the blood pressure in the lungs is about seven-fold lower than systemic blood pressure [92]. Further particularities of the pulmonary circulation can also be found in the thesis of Proença [118].
2.1.2 Factors Affecting Stroke Volume and Cardiac Output
The main factors affecting CO are illustrated in Figure 2.2. On the one hand, CO is proportional to the HR which in turn is decreased by parasympathetic activity, increased by sympathetic activity and further influenced by various hormones [92, 16]. On the other hand, CO is propor- tional to the SV which is mainly influenced by the three factors listed in the following:
1. Contractility(orinotropy) is the force of contraction of the heart muscle. It is mainly controlled by activity of the sympathetic nervous system and hormones. An increase in contractility leads to a more forceful contraction, which in turn leads to a higher SV through a decrease in end systolic volume (ESV).
2. Afterloadis defined as the load against which the ventricles have to contract to eject blood. It is closely linked to the total vascular resistanceRT and the mean arterial
pressure (MAP), i.e. an increase inRT leads to an increase in MAP which opposes
ventricular ejection and thus results in a reduced SV because of a higher ESV.
3. Preloadis an equivalent term for end diastolic volume (EDV). It determines to what extent the cardiac muscle is stretched prior to contraction. As stated by the law of
Frank-Starling: the higher this stretch the more powerful the contraction (increased contractility) and thus the higher the SV (until an optimal point is reached). Preload is influenced by venous return (i.e. venous blood flowing back to the heart) which in turn
is influenced by various factors such as the volume of circulating blood, respiration- induced changes in pressure or gravity.
Based on these mechanisms CO is regulated primarily to meet the metabolic demand of the different tissues in the body. For example, during exercise CO can rise five-fold of the baseline level to adequately supply the muscles with oxygen and other substances [92, 16]. In contrast, in patients suffering fromheart failure, CO is impaired which results in insufficient perfusion. Thiscardiac insufficiencyis due to damage or overloading of the heart which can be caused by diverse pathological conditions, of which two examples are given hereafter. First, in
cardiac ischemiathe blood supply of the heart muscle (myocardium) is restricted which results in decreased contractility. This is usually caused by obstructed blood flow in the coronary arteries (atherosclerosis) [16]. Second, elevated blood pressure (in the systemic or pulmonary circulation) leads to an increased afterload and thus impairs ventricular ejection. To cope with this situation the heart wall thickens (concentric hypertrophy) and eventually the affected ventricle begins to fail [92].
While the two abovementioned examples alter the CO usually over a longer period of time, there are situations in which the CO can be deteriorated within a short period. An example are patients who undergo high-risk surgical procedures. In this type of patients, the continuous monitoring and early optimization of their hemodynamic condition (including CO) after surgery has been shown to be very important as it results in significantly reduced mortality [89, 116]. These findings encourage the development of measurement devices which enable the continuous measurement of CO and do not necessitate invasive procedures such as right-heart catheterization (presented in the next section).