Three-dimensional echocardiography in coronary artery disease

Two-dimensional echocardiography has proven to be a very useful tool in the evaluation of global and regional left ventricular function in patients with coronary artcry disease. It has also been used in recognizing viable versus non-viable myocardium, combined with exercise or pharmacological stress. Recent development in transpulmonary ultrasound contrast agents inspired new interest in the cardiologists in myocardial perfusion imaging. Though most agents have proven helpful in (a few agents, including Optison and Leovist , have been approved for clinical application in several continents) left ventricular border delineation, their roles in myocardial perfusion imaging has not been studied extensively. The ability of two-dimensional methods in accurate assessment of the site and extent of wall motion and perfusion abnormalities is limited to the use of a few selected cross-sectional views of the left ventricle and employment of geometric assumptions of the ventricular cavity and walls. This leads to source of errors in quantitative studies of non-symmetric ventricles such as those undergone myocardial infarction and geometric remodeling. Twodimensional echocardiography is also limited in the evaluation of the mechanism of and in quantifying the severity of mitral regurgitation in patients with ischemic heart diseasc. Other complications of ischemic heart disease such as intracardiac thrombus can be diagnosed by two-dimensional echocardiography, but a more reproducible technique, such as three-dimensional echocardiography, may provide more reliable data on the therapeutic results in serial follow-up studies. Imaging of the blood vessels inc1uding coronary and carotid arteries has been relied mainly on invasive techniques. Two-dimensional ultrasound has shown limited promises in vascular imaging. Both the heart and the blood vessels are three-dimensional structures. An ideal approach in accurate and comprehensive examination of the heart and blood vessels is one that can collect volumetric information of the heart or vessels and is able to display them in three dimensions. Threedimensional echocardiography has demonstrated its superiority over two-dimensional methods in quantification of chamber volumes and function and in display of congenital or valvular abnormalities. Its role in the evaluation of coronary artery disease has not been fully explored. The purpose of this thesis was to examine the potential of three-dimensional echocardiography in qualitative and quantitative evaluation of coronary artery disease and related abnormalities

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world

Role of Computational Fluid Dynamics in the Analysis of Haemodynamic and Morphological Characteristics of Intracranial Aneurysms

Aneurysmal subarachnoid hemorrhage (SAH) carries a high morbidity and mortality. The current protocols used to treat the unruptured Intracranial Aneurysms (IAs) are inadequate underscoring the need of finding new descriptors. As demonstrated by the studies performed in this manuscript, haemodynamics plays an important role in the aetiopathogenesis of IAs. An evaluation of haemodynamic indices can provide a useful alternative to predict the behavior of an unruptured IA at an early stage. Studies performed by me demonstrate that Computational Fluid Dynamics (CFD) can be used successfully to predict haemodynamic indices where detailed in vivo measurement of haemodynamic flow variables is not possible owing to technical limitations. European Commission funded Project @neurIST was the first project of it’s kind that brought together a number of multidisciplinary professionals from 32 European institutions and made possible development of state-of-the-art tools for personalised risk assessment and treatment IAs using CFD. These tools have been constantly improved and amended in the light of feedback gathered from their controlled exposures conducted world over, as described in the manuscript. However, need of a well-designed Randomized Controlled Trial in this context cannot be overemphasized, before these tools can be accepted by clinicians and patients. In my study on the validation of different concepts used in CFD, I demonstrated that there is no added advantage of complex Womersley-flow-profile over the much simpler plug-flow profile. One of my studies on initiation and rupture of IAs showed that the haemodynamic patterns of IAs during these two phases are significantly different with values of supra-physiological Wall Shear Stress (WSS) being higher in initiation while lower in rupture phase. I also investigated the effects of pharmacological agents on the aetiopathogenesis of IAs and found that heparin induces significant derangements in the haemodynamics of both, pre-aneurysmal as well as ruptured IA. I propose that heparin (and its derivatives) can, on the one hand may facilitate the rupture of existing IAs, on the other hand they may suppress the formation of new IAs. I have also found significant differences in the results using patient-specific vs. Modeled Boundary Conditions and showed that the 1D circulation model adopted by @neurIST performs better than other approaches found in the literature. I also proposed a novel mechanism of increase in Blood Viscosity leading to high WSS as one of the important underlying mechanisms responsible for the increased incidence of IA formation in smokers and hypertensive patients. In my study on patients with pre-existing Coarctation of Aorta (CoA) and Intracranial Aneurysms, I demonstrated that the cerebral flow-rates in CoA patients were significantly higher when compared to average flow-rates in healthy population. It was also seen that the values and the area affected by supraphysiological WSS (>15Pa) were exponentially higher in patients with CoA indicating the possible role of increased haemodynamic WSS secondary to the increased flow-rates playing an important role in the pathogenesis and rupture of IAs in CoA patients

Doctor of Philosophy

dissertationIn this dissertation, the surface coating method/characteristics and a novel synthesis method for perfluorocarbon (PFC) emulsions were studied. These materials have relevance in a wide range of industrial and biomedical areas. Electrostatic coating of emulsions with poly-L-lysine (PLL) and chitosan (CS) was used to enhance the stability of the emulsions against phase separation. The ionic surfactant, 1,2-dioleoyl-sn-glycero-3-phosphate, DOPA, was used as an additive to the nonionic surfactant lecithin in order to increase the surface charge of the emulsion surface and facilitate accumulation of coating materials on the emulsion surface. Analysis of zeta potential versus pH was used to establish the best conditions for the coating process. The particle size and zeta potential was used to follow the coating progress. To characterize the final product, colorimetric determination was used to measure the bound/unbound fraction of PLL and CS and this was compared with a model-based analysis of zeta potential as a function of coating. Through this comparison and accounting for experimental error, a discrepancy in the effective particle number was revealed that was interpreted in terms of the compression and expansion of coating molecules on the surface as it assembles. Fluorescence quenching measurements using pyrene and fluorescein-doped emulsions supported the compression/expansion concept, resulting in more quenching when expansion of the coating took place. Thermodynamic analysis also supported these conformation changes and indicated a lowering of surface free energy for expanded coating. The second part of the dissertation reports a novel cosolvent method to synthesize PFOB emulsion with high yield production, in contrast to traditional extrusion methods that generate a large amount of water-filled liposomes as a side product. It was found that the selection of best cosolvent is related to its polarity relative to that of perfluorooctyl bromide (PFOB). Fourier transform infrared spectroscopy (FTIR) analyses were used to measure the retention of PFOB and revealed that nonpolar hexane has the best PFOB retention ability compared to methanol, ethanol, and chloroform. Moreover, phase transition temperatures (PTT) of the hexane/PFOB/lecithin system were observed at 13~19 °C and 22~24 °C by monitoring both the change in transparency by UV-Vis spectrophotometry and PFOB retention by FTIR. If emulsions are produced above the PTT (at 30 oC), PFOB is not retained. Quantitative measurement using FTIR for the best conditions gave 72% PFOB retention using the cosolvent method. Fluorescent and density analysis by centrifugation indicated that the traditional method for emulsion synthesis (directly emulsified) produced significantly more low-density water-filled liposomes than the cosolvent method. Higher density PFOB emulsion made with the cosolvent method can be easily separated and concentrated by centrifugation. The image of emulsions made by the traditional and cosolvent method could be viewed by cryogenic transmission electron microscopy