| 1. |
- Grishenkov, Dmitry, 1983-
(författare)
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Polymer-shelled Ultrasound Contrast Agents : Characterization and Application
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound-based imaging technique is probably the most used approach for rapid investigationand monitoring of anatomical and physiological conditions of internal organs and tissues.Ultrasound-based techniques do not require the use of ionizing radiation making the tests anexceptionally safe and painless. Operating in the frequency range between 1 to 15 MHz, medicalultrasound provides reliable visual and quantitative information from both superficial structuressuch as muscles and tendons, and also deeper organs such as liver and kidney. From the technicalpoint of view medical ultrasound has a good spatial and temporal resolution. Ultrasound machineis mobile or even portable, which makes it truly bedside modality. And last but not the least,ultrasound investigations are cheaper in comparison to other real time imaging techniques. Ultrasound imaging techniques can be greatly improved by the use of contrast agents to enhancethe signal from the area of interest (e.g. cardiac or liver tissues) relative to the background.Typically ultrasound contrast agent (UCA) is a suspension of the microbubbles consisting of agas core encapsulated within the solid shell. Generally these devices are injected systemically andfunction to passively enhance the ultrasound echo. In recent years, the UCAs have evolved frombeing just a visualization tool to become a new multifunctional and complex device for drug orgene therapy and targeted imaging. The overall objective of the project is to test novel polymer shelled microbubbles (MBs) as apossible new generation of ultrasound contrast agents. During the first year of the project an innovative criterion based on cross-correlation analysis toassess the pressure threshold at which ultrasonic waves fracture the polymer shell of microbubblehas been developed. In addition, acoustic properties of these microbubbles which are relevant totheir use both as contrast agents and drug carriers for localized delivery have been preliminarytested. Furthermore, in order to reconstruct viscoelastic properties of the shell the originalChurch’s model (1995) has been implemented. In collaboration with Karolinska Institutet, imagesof the microbubbles have been acquired with conventional imaging system. These imagesdemonstrate the potential of the novel polymer-shelled microbubbles to be used as contractenhancing agents. The objective of the second year was to describe the acoustic and mechanical properties ofdifferent types of microbubbles synthesised under varied conditions. This task was divided in twointerrelated parts. In the first part acoustic characterization has been completed in low intensityregion with the study of backscattered power, attenuation and phase velocity. In order torecalculate mechanical properties of the shell existing theoretical model has been furtheriimodified to accommodate the frequency dependence of viscoelastic properties andsimultaneously fit the attenuation and phase velocity data. The results concerning acoustic andmechanical properties of the microbubbles have been sent as a feedback to the manufacture inorder to optimize fabrication protocol for effective image acquisition. In the second part acousticcharacterization has been performed in high intensity region under varied parameters ofexperimental set-up. The results that illustrate the dependence of the fracture pressure thresholdon the system parameters allows us to discuss the potential role of polymer-shelled UCAs as drugcarriers and formulate the protocol for save, localized, cavitation-mediated drug delivery. For the third year the major task was to move on from the bulk volume in vitro tests towards themicrocapillary study and even further to incorporate the microcapillary into the tissue mimickingultrasound phantom. The last study has the objective to take into account the wave propagationthrough tissue. And last but not the least, the application of the polymer-shelled microbubblesfor evaluation of perfusion characteristics, i.e. capillary volume and velocity of the flow, has beenperformed. Similar tests are carried out with commercially available phospholipid-shelled UCA.Using destruction/replenishment technique it is suggested that the novel polymer-shelledmicrobubbles have a potential for a more accurate perfusion evaluation compared to that ofcommercially available phospholipid-shelled UCA. In conclusion, proposed polymer-shelled gas-core microbubbles provide a viable system to beused among the next generation of ultrasound contrast agents, which facilitate not only imageenhancement relevant to diagnostics but also localized and specific drug delivery for non-invasivetherapy even in acute conditions.
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| 2. |
- Sturm, Dennis
(författare)
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Wireless Multi-Sensor Feedback Systems for SportsPerformance Monitoring : Design and Development
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Wireless applications have become a common part of daily life. Whether it is mobile phones, the Wi-Fi router at home, the keycard which has replaced the car key, a radio frequency identification access system to a building or a Bluetooth headset for your computer or phone, the means of modern wireless data exchange is an omnipresent technology. In sports, the market is in its infancy for wireless, technical applications or gadgets. Only heart rate monitors and GPS watches are currently used by recreational athletes. Even though most of the larger sports equipment companies regularly launch new products related to sports performance monitoring and mobile phone technology, product innovation leaps are rare.In this work the design of a wireless sports performance measurement platform is presented. Using the example of kayaking, this platform is configured as a paddle performance measuring system, the Kayak XL System, which can monitor propulsive paddle force, paddle kinematics and boat velocity, interalia. A common mobile phone platform has been chosen as the user interface for this system. The design approach focussing on user requests, demands and expectations in combination with the process of iterative technical development are unveiled in this thesis. An evaluation of the system is presented and the work is finalised with an overview of further systems which have been designed based on the developed measurement platform. The Kayak XL System is a flexible system designed to be mounted onto any standard kayak paddle and installed in any competition kayak. Versatility, unobtrusiveness and usability were major design concerns. The developed system consists of four modules plus a software which has been designed for Android mobile phones. The phone communicates with each of the four modules trough Bluetooth radio. These four modules are also referred to as nodes and have specific measurement purposes. Two nodes have been designed to measure paddle force and kinematics, one node has the purpose to measure foot stretcher force and boat motion data, and the fourth node enables a more convenient method of calibrating paddle force measurement. The fourth node is therefore only needed prior to performance data acquisition. Results show that paddle and foot stretcher force can be measured with a resolution below 1N after calibration. Installing the paddle nodes on a previously configured paddle without repeated calibration is facilitated with the compromise of a doubled error margin. The default sampling frequency is set to 100 Hz and can, like all system parameters, be configured on the mobile phone. Real-time computation of complex performance parameters is only limited by the phone CPU. The system adds twice 109 g to the paddle and approximately 850 g to the kayak, excluding the mass of the mobile phone
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| 3. |
- Elmstedt, Nina
(författare)
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Prenatal Tisse Velocity Imaging of the Heart : A new approach to assess fetal myocardial function
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis has been to evaluate color‐coded tissue velocity imaging (TVI) as an approach to developing a new, non‐invasive assessment method for fetal myocardial function. Such a method could hypothetically give early indications of fetal pathology, as myocardial dysfunction is often the consequence when the circulation tries to adapt to deteriorating situations. This would be beneficial in clinical decision making when evaluating fetal well‐being in a wide range of pregnancy associated conditions, to facilitate risk assessment and to monitor the benefit of therapeutic interventions.TVI is an ultrasound technique that enables quantification of longitudinal myocardial motion with high temporal resolution, which is essential in the identification of fetal myocardial movements of short duration. Furthermore, the longitudinal motion is mainly determined by subendocardial fibers that usually become abnormal in the very early stages of cardiac dysfunction as they are sensitive to milder degrees of hypoxia. Thus, TVI has the potential to give early indications of impaired fetal myocardial function and hypothetically facilitate the detection of intrauterine hypoxia. Hypoxia is a common phenomenon of many pathological conditions in pregnancy, from which a substantial number of children either die or acquire permanent brain injury during delivery every year.After having established optimal sampling requirements and ensured an acceptable reproducibility for TVI measurements of the fetal myocardium, normal reference values were determined feasible and sensitive enough to provide insight into maturational changes in myocardial function. This provided a foundation that should enable further investigations and was partly accomplished using the cardiac state diagram (CSD) to accurately time the myocardial events during a cardiac cycle according to the motion shifts of the atrioventricular plane.The demonstrated results are promising and the general conclusion of this thesis is that TVI contributes to increasing the knowledge and understanding of fetal myocardial function and dysfunction. Used together with CSD this technique has great potential as an assessment method. However, further testing of the clinical potential is needed in larger study populations concerning the pathological or physiological questions at issue, and additional development of the method is required to render the method simple enough to be of potential aid in clinical practice.
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| 4. |
- Manouras, Aristomenis, 1974-
(författare)
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Tissue Doppler in Spectral and Color ModeMethodological ConsiderationsNon-invasive Estimation of Left Ventricular Filling Pressures using the E/Em index
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Tissue Doppler (TD) in spectral mode (spectral TD) and color TD are the two modalities available today in tissue velocity echocardiography (TVE). Measurements of left ventricular (LV) myocardial velocities and displacement may yield different results depending on the employed sonographic modality and the subjective adjustments during data analysis. The ratio of transmitral early diastolic velocity (E) to early diastolic myocardial velocity (Em) has been suggested as a non-invasive estimate of LV filling pressures. The present studies aimed to evaluate the compatibility between the two TD modalities and the effect of temporal filtering and offline gain on velocity and displacement measurements obtained using these two methods. The validity of E/Em in identifying elevated LV filling pressures after acute reductions in hemodynamic LV loading was assessed. Methods and Results: In 57 patients, longitudinal myocardial velocity profiles were acquired from the basal LV segments, using spectral and color TD. Peak systolic (Sm) and early diastolic (Em) myocardial velocities and the myocardial displacement during the ejection phase were measured offline. Spectral TD measurements were performed using three different gain settings (0%-, 50%- 100% offline gain). Color TD analysis were performed before and after the application of temporal filtering at 30, 50 and 70 ms filter width. The E/Em ratio was calculated at the different settings. The correlation between spectral- and color TD measurements was good. Changes in offline gain and filter width resulted in significant alterations on spectral and color TD derived measurements, respectively. Sm and Em were significantly higher (p < 0.001) whereas the E/Em was significantly lower (p < 0.001) for measurements performed with spectral TD compared to color TD and the discrepancy among the measurements increased at increasing filter width and gain level. In Study II the results of spectral- and color TD derived displacement were compared to anatomic M-mode. Spectral TD at different gain settings significantly overestimated M-mode derived displacement measurements, whereas the concordance between color TD and M-mode was considerably better. In Study III, LV longitudinal systolic myocardial velocities and displacement during ejection period were quantified at the basal septal and lateral wall in 24 healthy individuals using spectral TD, color TD and M-mode. Mean spectral TD systolic velocity and displacement values were obtained from the outer and inner borders of the spectral velocity signal. The estimated mean spectral TD systolic myocardial velocities were highly concordant with corresponding color TD measurements (mean difference 0.1 ± 0.6 cm/s, septal wall; 0.1 ± 1.0 cm/s, lateral wall). Similarly, myocardial displacement obtained by integration over time of mean spectral TD velocities was in good agreement with color TD (mean difference 0.2 ± 0.7 mm, septal wall; 0.02 ± 0.86 mm, lateral wall) as well as with the corresponding M-mode measurements. In Study IV, simultaneous LV catheterization and echocardiographic examination was performed in 68 consecutive patients referred for coronary angiography. Doppler signals of the transmitral flow and spectral TD signals at the level of mitral annulus were obtained and the E/Em was then calculated. All examinations were repeated after nitroglycerin (NTG) infusion. At baseline, the predictive ability of E/Em in identifying elevated LVDP was modest at best (area under curve [AUC] ± SE = 0.71 ± 0.08, p < 0.01). The index was more strongly associated with LVDP in patients with reduced ejection fraction (EF) < 55% (r = 0.68; p < 0.01) compared to patients with EF ≥ 55%(r = 0.4; p < 0.05). Following NTG administration, the diagnostic ability of E/Em in detecting elevated LVDP was significantly reduced (area under curve [AUC] ± SE =0.6 ± 0.08, p > 0.05). Changes in LVDP were not reliably tracked using E/Em (p > 0.05). Conclusions: Spectral TD yields significantly higher myocardial velocity and displacement values and lower E/Em compared to color TD modality. Increasing gain and temporal smoothing significantly alters the obtained velocity and displacement information and yield greater disparity between measurements derived using the two TD methods. Spectral TD significantly overestimates myocardial displacement obtained using M-mode. On the other hand, the agreement between color TD and anatomic M-mode is considerably better. Measurements based on mean spectral TD velocities were highly concordant with those provided by color TD and M-mode. However, unfavorable limits of agreement discourage the interchangeable use of these modalities. The diagnostic ability of E/Em was poor and declined significantly following acute reduction in LV hemodynamic loading. Changes in LVDP were not predicted by alterations in E/Em. Our findings imply that E/Em might not be sufficiently robust to be employed as a single non-invasive estimate for tailoring medical therapy in patients with elevated LVDP.
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| 5. |
- A'roch, Roman, 1959-
(författare)
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Left ventricular function's relation to load, experimental studies in a porcine model
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Loading conditions are recognized to influence ventricular function according to the Starling relationship for length/stretch and force. Many modern echocardiographic parameters which have been announced as describing ventricular function and contractile status, may be confounded by uncontrolled and unmeasured load. These studies aimed to measure the relation between four different types of assessments of ventricular dysfunction and degrees of load. Study examined the ‘myocardial performance index’ (MPI). Study II examined long axis segmental mechanical dyssynchrony. Study III examined tissue velocities, and Study IV examined ventricular twist. All studies aimed to describe the relation of these parameters both to load and to inotropic changes. Methods: In anesthetized juvenile pigs, left ventricular (LV) pressure and volume were measured continuously and their relationship (LVPVR) was analysed. Preload alterations were brought about by inflation of a balloon tipped catheter in the inferior vena cava (IVCBO). Inotropic interventions were brought about by either an overdose of anesthetic (combine intravenous pentobarbital and inhaled isoflurane, Study I), or beta blocker and calcium channel blocker given in combination (Studies III and IV). In one study (II), global myocardial injury and dysfunction was induced by endotoxin infusion. MPI measurements were derived from LVPVR heart cycle intervals for isovolumic contraction and relaxation as well as ejection time. Long axis segmental dyssynchrony was derived by analyzing for internal flow and time with segmental dyssynchronous segment volume change during systole, hourly before and during 3 hours of endotoxin infusion. Myocardial tissue velocities were measured during IVCBO at control, during positive and then later negative inotropic interventions. The same for apical and base circumferential rotational velocities by speckle tracking. Load markers (including end-diastolic volume) were identified for each beat, and the test parameters were analysed together with load for a relation. The test parameters were also tested during single apneic beats for a relation to inotropic interventions. Results: MPI demonstrated a strong and linear relationship to both preload and after-load, and this was due to changes in ejection time, and not the isovolumic intervals. Long axis segmental dyssynchrony increased during each hour of endotoxin infusion and global myocardial injury. This dysynchrony parameter was independent of load when tested by IVCBO. Peak systolic velocities were strongly load-independent, though not in all the inotropic situations and by all measurement axes. Peak systolic strain was load-dependent, and not strongly related to inotropic conditions. Peak systolic LV twist and untwist were strongly load-dependent. Conclusions: MPI is strongly load-dependent, and can vary widely in value for the same contractile status if the load is varied. Mechanical dyssynchrony measures are load-independen in health and also in early global endotoxin myocardial injury and dysfunction. Peak sytole velocities are a clinically robust parameter of LV regional and global performance under changing load, though peak systolic strain seems to be load-dependent. Left ventricular twist and untwist are load-dependent in this pig model.
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| 6. |
- Kothapalli, VeeraVenkata Satyanarayana, 1985-
(författare)
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Ultrasound Contrast Agents Loaded with Magnetic Nanoparticles : Acoustic and Mechanical Characterization
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The current methodologies in body scanning diagnostic uses different simultaneous imaging modalities like Ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPECT) and positron emission tomography (PET). The field requires combination of different modalities for effective use in clinical diagnostics. Such incorporation of different modalities has already been achieved. For example, PET-CT hybrid scanner is designed to acquire align functional and anatomical images and recently US-MRI scanner has successfully shown to improve diagnosis of prostate cancer. The non ionizing radiation hybrid US-MRI is of great interest in health care industry. Further these US and MRI modalities uses different contrast agents like micro-sized gas bubbles (MBs) encapsulated by surfactant for US and superparamagnetic nanoparticles for MRI imaging modalities to further enables new diagnostic opportunities and therapeutic applications. Recently in our 3MiCRON project, we have developed the multimodal contrast agent that could be supported for both US and MRI. This was achieved by coating the magnetic nanoparticles to the poly vinyl alcohol (PVA) surfactant shelled MBs. The nanoparticles in the shell effect the structure can alter the MBs performance as an ultrasound contrast agent. The present thesis is conducted to examine the acoustic and mechanical properties of such multimodal contrast agents.These multimodal contrast agents were prepared by coating the surface of PVA-shelled MBs by two following strategies: (1) The superparamagnetic iron oxide (Fe3O4) nano-particles (SPIONs) were chemically anchored to the surface of poly vinyl alcohol (PVA) shelled MBs namely MBs-chem and (2) in the second strategy the SPIONs were physical entrapped into the PVA shell while formation of PVA surface on the gas bubble were named as MBs-phys. To understand the scattering efficiency and viscoelastic properties of these modified agents, we investigated the backscattering power, attenuation coefficient and phase velocity measurements. Our acoustic experimental results indicate that both the modified MBs and non-modified plain PVA-shelled ultrasound contrast agents have the same echogenic response. The investigation of mechanical properties of modified MBs revealed that the attached SPIONs on the PVA shell has reduced the stiffness of MBs-chem shell, while, the SPIONs inside the shell has increased MBs-phys stiffness. As a result, MBs-chem exhibits soft shell behavior under ultrasound exposure than both MBs-phys. Finally, the images were obtained through the MRI investigations at the department of Radiology, Karolinksa Institute, has demonstrated that both MB types have enough magnetic susceptibility that further provides good detectability in vitro and in vivo. As an outlook, the modified magnetic gas bubbles, i.e. both MBs-chem and MBs-phys can be proposed as a potential contrast agent for both US and MR imaging and can be further utilized in potential therapeutic applications.
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| 7. |
- Lindberg, Frida, 1982-
(författare)
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Ultrasonic Quantification of Skeletal Muscle Dynamics : Feasibility and Limitations
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pain and disorders of the human skeletal muscles are one of the most common reasons for medical consultations in the western countries today and there is a great need to improve both the understanding and treatment of several different muscular conditions.Techniques describing the muscle function in vivo are often limited by either their invasiveness or lack of spatial resolution. Electromyography (EMG) is the most common approach to assess the skeletal muscle function in vivo, providing information on the neurological input. However, the spatial resolution is in general limited and there are difficulties reaching deep musculature without using invasive needles. Moreover, it does not provide any information about muscle structure or mechanical aspects.Quantitative ultrasound techniques have gained interest in the area of skeletal muscles and enables non-invasive and in-vivo insight to the intramuscular activity, through the mechanical response of the activation. However, these techniques are developed and evaluated for cardiovascular applications and there are important considerations to be made when applying these methods in the musculoskeletal field. This thesis is based on the work from four papers with the main focus to investigate and describe some of these considerations in combination with the development of processing and analyzing methods that can be used to describe the physiological characteristics of active muscle tissue.In the first paper the accuracy of the Doppler based technique Tissue Velocity Imaging (TVI) was evaluated in a phantom study for very low tissue velocities and the effect of the pulse repetition frequency was considered. The second paper presents a biomechanical model to describe the TVI strain’s dependency on the muscle fiber pennation angle. In the third and fourth papers the intramuscular activity pattern was assessed through the regional tissue deformation by motion mode (M-mode) strain imaging. The activity patterns were analyzed during force regulation and for the effects of fatigue.The work of this thesis show promising results for the application of these methods on skeletal muscles and indicate high clinical potential where quantitative ultrasound may be a valuable tool to reach a more multifaceted and comprehensive insight in the musculoskeletal function. However, the methodological considerations are highly important for the optimized application and further evaluation and development of analyzing strategies are needed.
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| 8. |
- Mårtensson, Mattias
(författare)
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Evaluation of Errors and Limitations in Ultrasound Imaging Systems
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are binding regulations requiring safety and efficacy aspects of medical devices. The requirements ask for documentation that the devices are safe and effective for their intended use, i.e. if a device has a measuring function it must be correct. In addition to this there are demands for quality systems describing development, manufacturing, labelling, and manufacturing of a device. The requirements are established to guarantee that non-defective medical devices are used in the routine clinical practice. The fast rates in which the imaging modalities have evolved during the last decades have resulted in numerous new diagnostic tools, such as velocity and deformation imaging in ultrasound imaging. However, it seems as if the development of evaluation methods and test routines has not been able to keep up the same pace. Two of the studies in this thesis, Study I and IV, showed that computed tomography-based and ultrasound based volume measurements can yield very disparate measurements, and that tissue Doppler imaging-based ultrasound measurements can be unreliable. Furthermore, the new ultrasound modalities impose higher demands on the ultrasound transducers. Transducers are known to be fragile, but defective transducers were less of a problem earlier when the ultrasound systems to a lesser extent were used for measurements. The two other studies, Study II and III, showed that serious transducer errors are very common, and that annual testing of the transducers is not sufficient to guarantee an error free function. The studies in the thesis indicate that the system with Notified Bodies, in accordance with the EU’s Medical Device Directive, checking the function and manufacturing of medical devices does not work entirely satisfactory. They also show that the evaluation of new methods have led to the undesirable situation, where new measuring tools, such as volume rendering from imaging systems, and tissue Doppler-based velocity and deformation imaging in echocardiography are available for clinicians without proven knowledge about their accuracy.
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| 9. |
- Shahgaldi, Kambiz, 1978-
(författare)
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Assessment of Left Ventricular Function and Hemodynamics Using Three-dimensional Echocardiography
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Left ventricular (LV) volumes and ejection fraction (EF) are important predictors of cardiac morbidity and mortality. LV volumes provide valuable prognostic information which isparticularly useful in the selection of therapy or determination of the optimal time for surgery. Two-dimensional (2D) echocardiography is the most widely used non-invasive method forassessment of cardiac function, 2D echocardiography has however several limitations inmeasuring LV volumes and EF since the formulas for quantifications are based on geometricalassumptions. Three-dimensional (3D) echocardiography has been available for almost twodecades, although the use of this modality has not gained wide spread acceptance. 3D echocardiography can overcome the above mentioned limitation in LV volume and EF evaluation since it is not based on geometrical assumption. 3D echocardiography has been shownin several studies to be more accurate and reproducible with low inter- and intraobservervariability in comparison to 2D echocardiography regarding the measurements of LV volumesand EF. The overall aim of the thesis was to evaluate the feasibility and accuracy of 3D echocardiography based-methods in the clinical context. In Study I the feasibility of 3D echocardiography was investigated for determination of LV volumes and EF using parasternal, apical and subcostal approaches. The study demonstrated that the apical 3D echocardiography view offers superior visualization. Study II tested the possibility of creating flow-volume loops to differentiate patients with valvular abnormalities from normal subjects. There were significant differences in the pattern from flow-volume loops clearly separating the groups. In Study III the visual estimation, “eyeballing” of EF was evaluated with two- and tri-plane echocardiography in comparison to quantitative 3D echocardiography. The study confirmed that an experienced echocardiographer can, with a high level of agreement estimate EF both with two- and tri-plane echocardiography. Study IV exposed the high accuracy of stroke volume and cardiac output determination using a3D biplane technique by planimetrically tracing the left ventricular outflow tract and indicating that an assumption of circular left ventricular outflow tract is not reliable. In Study V, two 3D echocardiography modalities, single-beat and four-beat ECG-gated 3D echocardiography were evaluated in patients having sinus rhythm and atrial fibrillation. Thesingle-beat technique showed significantly lower inter-and intraobserver variability in LV volumes and EF measurements in patients having atrial fibrillation in comparison to four-beat ECG-gated acquisition due to absence of stitching artifact. All studies demonstrated good results suggesting 3D echocardiography to be a feasible andaccurate method in daily clinical settings.
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