| 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. |
- Frånberg, Oskar, 1976-
(författare)
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Oxygen content in semi-closed rebreathing apparatuses for underwater use : Measurements and modeling
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present series of unmanned hyperbaric tests were conducted in order to investigate the oxygen fraction variability in semi-closed underwater rebreathing apparatuses. The tested rebreathers were RB80 (Halcyon dive systems, High springs, FL, USA), IS-Mix (Interspiro AB, Stockholm, Sweden), CRABE (Aqua Lung, Carros Cedex, France), and Viper+ (Cobham plc, Davenport, IA, USA). The tests were conducted using a catalytically based propene combusting metabolic simulator. The metabolic simulator connected to a breathing simulator, both placed inside a hyperbaric pressure chamber, was first tested to demonstrate its usefulness to simulate human respiration in a hyperbaric situation. Following this the metabolic simulator was shown to be a useful tool in accident investigations as well as to assess the impact of different engineering designs and physiological variables on the oxygen content in the gas delivered to the diver by the rebreathing apparatuses. A multi-compartment model of the oxygen fractions was developed and compared to the previously published single-compartment models. The root mean squared error (RMSE) of the multi-compartment model was smaller than the RMSE for the single-compartment model, showing its usefulness to estimate the impact of different designs and physiological variables on the inspired oxygen fraction.
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| 5. |
- Kothapalli, Satya V.V.N. 1985-
(författare)
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Nano-Engineered Contrast Agents : Toward Multimodal Imaging and Acoustophoresis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diagnostic ultrasound (US) is safer, quicker and cheaper than other diagnostic imaging modalities. Over the past two decades, the applications of US imaging has been widened due to the development of injectable, compressible and encapsulated microbubbles (MBs) that provide an opportunity to improve conventional echocardiographic imaging, blood flow assessment and molecular imaging. The encapsulating material is manufactured by different biocompatible materials such as proteins, lipids or polymers. In current research, researchers modify the encapsulated shell with the help of advanced molecular chemistry techniques to load them with dyes (for fluorescent imaging), nanoparticles and radioisotopes (for multimodal imaging) or functional ligands or therapeutic gases (for local drug delivery). The echogenicity and the radial oscillation of MBs is the result of their compressibility, which undoubtedly varies with the encapsulated shell characteristics such as rigidity or elasticity.In this thesis, we present acoustic properties of novel type of polyvinyl alcohol (PVA)-shelled microbubble (PVA-MB) that was further modified with superparamagnetic iron oxide nanoparticles (SPIONs) to work as a dual-modal contrast agent for magnetic resonance (MR) imaging along with US imaging. Apparently, the shell modification changes their mechanical characteristics, which affects their acoustic properties. The overall objective of the thesis is to investigate the acoustic properties of modified and unmodified PVA-MBs at different ultrasound parameters.The acoustic and mechanical characterization of SPIONs modified PVA-MBs revealed that the acoustical response depends on the SPION inclusion strategy. However they retain the same structural characteristics after the modification. The modified MBs with SPIONs included on the surface of the PVA shell exhibit a soft-shelled behavior and produce a higher echogenicity than the MBs with the SPIONs inside the PVA shell. The fracturing mechanism of the unmodified PVA-MBs was identified to be different from the other fracturing mechanisms of conventional MBs. With the interaction of high-pressure bursts, the air gas core is squeezed out through small punctures in the PVA shell. During the fracturing, the PVA-MBs exhibit asymmetric (other modes) oscillations, resulting in sub- and ultra-harmonic generation. Exploiting the US imaging at the other modes of the oscillation of the PVA-MBs would provide an opportunity to visualize very low concentrations of (down to single) PVA-MBs. We further introduced the PVA-MBs along with particles mimicking red blood cells in an acoustic standing-wave field to observe the acoustic radiation force effect. We observed that the compressible PVA-MBs drawn toward pressure antinode while the solid blood phantoms moved toward the pressure node. This acoustic separation method (acoustophoresis) could be an efficient tool for studying the bioclearance of the PVA-MBs in the body, either by collecting blood samples (in-vitro) or by using the extracorporeal medical procedure (ex-vivo) at different organs.Overall, this work contributes significant feedback for chemists (to optimize the nanoparticle inclusion) and imaging groups (to develop new imaging sequences), and the positive findings pave new paths and provide triggers to engage in further research.
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| 6. |
- Larsson, Matilda, 1981-
(författare)
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Quantification and Visualization of Cardiovascular Function using Ultrasound
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Bjällmark, Anna, 1980-
(författare)
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New ultrasonographic approaches to monitoring cardiac and vascular function
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerotic cardiovascular disease is the leading cause of death worldwide. To decrease mortality and morbidity in cardiovascular disease, the development of accurate, non-invasive methods for early diagnosis of atherosclerotic cardiac and vascular engagement is of considerable clinical interest. Cardiovascular ultrasound imaging is today the cornerstone in the routine evaluation of cardiovascular function and recent development has resulted in two new techniques, tissue velocity imaging (TVI) and speckle tracking, which allow objective quantification of cardiovascular function. TVI and speckle tracking are the basis for three new approaches to cardiac and vascular monitoring presented in this thesis: wave intensity wall analysis (WIWA), two-dimensional strain imaging in the common carotid artery, and the state diagram of the heart. WIWA uses longitudinal and radial strain rate as input for calculations of wave intensity in the arterial wall. In this thesis, WIWA was validated against a commercially available wave intensity system, showing that speckle tracking-derived strain variables can be useful in wave intensity analysis. WIWA was further tested in patients with end stage renal disease and documented high mortality in cardiovascular disease. The latter study evaluated the effects of a single session of hemodialysis using WIWA and TVI variables and showed improved systolic function after hemodialysis. The results also indicated that preload-adjusted early systolic wave intensity obtained by the WIWA system may contribute in the assessment of left ventricular contractility in this patient category. Two-dimensional strain imaging in the common carotid artery is a new approach showing great potential to detect age-dependent differences in mechanical properties of the common carotid artery. Among the measured strain variables, global circumferential strain had the best discriminating performance and appeared to be superior to conventional measures of arterial stiffness such as elastic modulus and β stiffness index. The state diagram is a visualisation tool that provides a quantitative overview of the temporal interrelationship of mechanical events in the left and right ventricles. Case examples and a small clinical study showed that state diagrams clearly visualize cardiac function and can be useful in the detection of non ST-elevation myocardial infarction (NSTEMI). Even though WIWA, two-dimensional strain imaging in the common carotid artery and the state diagram show potential to be useful in the evaluation of cardiovascular function, there still remains a considerable amount of work to be done before they can be used in the daily clinical practice.
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| 10. |
- 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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