Bibliography: leaves 148-166. / xi, 166 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The chicken embryo's ability to match the perfusion of its chorioallantoic membrane to regional differences in shell conductance was investigated. / Thesis (Ph.D.)--Adelaide University, Dept. of Environmental Biology, 2001

Carotid artery wall stiffness has been widely considered as an index of vascular health, and has been associated with occurrence of cardiovascular events, such as stroke. In addition, the blood flow patterns in the carotid artery can yield crucial information on atherosclerosis progression and cerebrovascular impairment. Pulse wave imaging (PWI) is a non-invasive ultrasound imaging technique that tracks the propagation of the arterial pulse wave, providing thus regional arterial wall stiffness mapping. Moreover, towards enabling accurate visualization of blood flow patterns, ultrasound-based vector flow imaging (VFI) modalities have been developed. Building upon PWI and VFI techniques, the overall goal of this dissertation is to develop ultrasound-based methodologies that can provide simultaneous imaging of the carotid artery wall mechanics and blood flow dynamics at high temporal and spatial resolutions. The developed techniques are validated through vessel phantom experiments and simulations. Furthermore, their potential to diagnose pre-clinical stages of carotid artery disease and provide additional insights in risk for stroke assessment, is demonstrated in an atherosclerotic swine study and human subjects in vivo. More specifically: A method is presented that analyzes the pattern of arterial wall motion derived by PWI, in order to detect spatial mechanical inhomogeneity across an imaged artery, and provide piecewise arterial wall stiffness estimates. The proposed technique is validated in a phantom consisting of a soft and a stiff segment, while its feasibility is demonstrated to identify inhomogeneous wall properties in atherosclerotic human carotid arteries, as well as provide atherosclerotic plaque mechanical characterization in vivo. Subsequently, PWI is integrated with VFI techniques in the same ultrasound acquisition sequence, in order to enable simultaneous and co-localized imaging of arterial wall stiffness and blood vector flow velocity. The performance of the technique is investigated through experiments and FSI simulations. Moreover, its feasibility was shown to investigate associations between carotid artery Pulse Wave Velocity and blood flow patterns, in vivo. Based on the previously developed PWI and VFI modalities, a novel ultrasound-based technique is developed that combines high frame rate vector flow imaging with a data clustering approach, in order to enable direct and robust wall shear stress measurements. The performance of the proposed method is evaluated through vessel phantom experiments and simulations, while its feasibility is shown to detect pre-clinical stages of carotid artery disease in a swine model in vivo. In addition, a pilot clinical study is presented involving application of the developed modality in normal and atherosclerotic human carotid arteries in-vivo. Moving forward, the developed imaging modalities are used to implement novel clinical biomarkers based on carotid artery arterial wall mechanics and blood flow dynamics, that can potentially assist in risk for stroke assessment. The patterns of those biomarkers are investigated in the common carotid arteries of subjects with low degree of stenosis and medical history of stroke, against subjects without history of stroke. The same biomarkers are also analyzed with respect to stroke symptomatology in atherosclerotic patients with moderate to high degree of stenosis. Moreover, the developed techniques are used to identify vulnerable plaque components in subjects with fully developed plaques, as compared with CTA scans. Finally, a deep learning-based approach for motion tracking of the arterial wall throughout the cardiac cycle is proposed. A neural network is trained to learn the motion patterns of the carotid artery and potentially improve the quality of PWI. The performance of the technique is assessed in vessel phantom experiments and its feasibility is demonstrated in healthy human carotid arteries in-vivo.

This dissertation develops uncertainty quantification methodologies for modeling, response analysis and optimization of diverse dynamical systems. Two distinct application platforms are considered pertaining to engineering dynamics and precision medicine. First, the recently developed Wiener path integral (WPI) technique for determining, accurately and in a computationally efficient manner, the stochastic response of diverse dynamical systems is employed for solving a high-dimensional, nonlinear system of stochastic differential equations governing the dynamics of a representative model of electrostatically coupled micromechanical oscillators. Compared to alternative modeling and solution treatments in the literature, the current development exhibits the following novelties: a) typically adopted linear, or higher-order polynomial, approximations of the nonlinear electrostatic forces are circumvented; and b) stochastic modeling is employed, for the first time, by considering a random excitation component representing the effect of diverse noise sources on the system dynamics. Further, the WPI technique is enhanced and extended based on a Bayesian compressive sampling (CS) treatment. Specifically, sparse expansions for the system response joint PDF are utilized. Next, exploiting the localization capabilities of the WPI technique for direct evaluation of specific PDF points leads to an underdetermined linear system of equations for the expansion coefficients. Furthermore, relying on a Bayesian CS solution formulation yields a posterior distribution for the expansion coefficient vector. In this regard, a significant advantage of the herein-developed methodology relates to the fact that the uncertainty of the response PDF estimates obtained by the WPI technique is quantified. Also, an adaptive scheme is proposed based on the quantified uncertainty of the estimates for the optimal selection of PDF sample points. This yields considerably fewer boundary value problems to be solved as part of the WPI technique, and thus, the associated computational cost is significantly reduced. Second, modeling and analysis of the physiological mechanism of dynamic cerebral autoregulation (DCA) is pursued based on the concept of diffusion maps. Specifically, a state-space description of DCA dynamics is considered based on arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. The reliability of the technique is assessed by considering healthy individuals and patients with unilateral carotid artery stenosis or occlusion. It is shown that the proposed ratio of eigenvalues can be used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function. Further, an alternative joint time-frequency analysis methodology based on generalized harmonic wavelets is utilized for assessing DCA performance in patients with preeclampsia within one week postpartum, which is associated with an increased risk for postpartum maternal cerebrovascular complications. The results are compared with normotensive postpartum individuals and healthy non-pregnant female volunteers and suggest a faster, but less effective response of the cerebral autoregulatory mechanism in the first week postpartum, regardless of preeclampsia diagnosis.

La mesure et le contrôle du pouls et du flux sanguin en continu sont d'importants paramètres pour l'évaluation de signes essentiels physiologiques sur la condition de santé d'un individu. Les dispositifs commerciaux existants, ainsi que les méthodes de recherche ou utilisées dans le milieu médical exigent un bon contact électrique ou optique pour obtenir cette mesure en continu. Pendant ces travaux de recherche, une méthode originale non invasive de mesure du rythme cardiaque fondée sur la perturbation localisée d'un champ magnétique au passage du flux sanguin a été développée, permettant l'acquisition des signaux à travers les vêtements, la transpiration, les salissures ou autres polluants dans l'environnement proche du capteur. Cette méthode est appelée la Signature Sanguine par Modulation Magnétique (MMSB) et les mesures ont été accomplies sur de multiples individus. Le système a été modélisé mathématiquement et simulé dans un environnement multiphysique, puis validé par l'utilisation des données expérimentales. Les résultats de mesure, en utilisant la méthode MMSB, pour le pouls et le flux sanguin ont été comparés et se trouvent bien corrélés, avec les résultats obtenus grâce à d'autres instruments. De plus, deux dispositifs ont été développés et sont en cours de commercialisation, pour des applications de vie quotidienne / Continuous pulse rate, blood pressure and blood flow monitoring are important for the assessment of physiological vital signs as these are able to provide continuous feedback on the health condition of an individual. Existing commercial, medical and research methods to continuously acquire such these physiological vital signs require good electrical or optical contact. During this research, a magnetic based sensing method, at room temperature, for blood pulse, flow and pressure is developed to achieve data acquisition through fabric, environmental contaminants and body-fluids. This method is named Modulated Magnetic Signature of Blood (MMSB) and physical measurements were conducted on multiple subjects, mathematically modelled and simulated in a multi-physics environment with verification through use of measurement data. Measurement results, using MMSB, for blood pressure and blood flow were compared, and found to be well correlated, with lifestyle device and medical research instruments respectively. In addition, two devices are developed, and are in the midst of commercialization, to support lifestyle applications

Peng Zhiyong. / "December 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 146-175) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

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Wall shear stress (WSS) has long been identified as a factor in the development of atherosclerotic lesions. Autopsy studies have revealed a strong tendency for lesion development at arterial branch sites and along the inner walls of curvature areas that, in theory, should experience low WSS. Calculations of coronary artery WSS have typically been based upon average models of coronary artery geometry with average flow conditions and then compared to average lesion distributions. With all the averaging involved, a more detailed knowledge of the correlation between WSS and atherosclerotic lesion development might be obscured. Recent advancements in hemodynamic modeling now enable the calculation of WSS in individual subjects. An image-based approach for patient-specific calculation of in vivo WSS using computational fluid dynamics (CFD) would allow a more direct study of this correlation. New state-of-the-art technologies in multi-detector computed tomography (CT) and 3.0 Tesla magnetic resonance imaging (MRI) offer potential improvements for the measurement of coronary artery geometry and blood flow. The overall objective of this research was to evaluate the quantitative accuracy of multi-detector CT and 3.0 Tesla MRI and incorporate those imaging modalities into a patient-specific CFD model of coronary artery WSS. Using a series of vessel motion phantoms, it has been shown that 64-detector CT can provide accurate measurements of coronary artery geometry for heart rates below 70 beats per minute. A flow phantom was used to validate the use of navigator-echo gated, phase contrast MRI at 3.0 Tesla to measure velocity of coronary blood flow. Patient-specific, time-resolved CFD models of coronary WSS were created for two subjects. Furthermore, it was determined that population-average velocity curves or steady state velocities can predict locations of high or low WSS with high degrees of accuracy compared to the use of patient-specific blood flow velocity measurements as CFD boundary conditions. This work is significant because it constitutes the first technique to non-invasively calculate in vivo coronary artery WSS using image-based, patient-specific modeling.

Indiana University-Purdue University Indianapolis (IUPUI) / Atherosclerotic lesions of human beings are common diagnosed in regions of arte- rial branching and curvature. The prevalence of atherosclerosis is usually associated with hardening and ballooning of aortic wall surfaces because of narrowing of flow path by the deposition of fatty materials, platelets and influx of plasma through in- timal wall of Aorta. High Wall Shear Stress (WSS) is proved to be the main cause behind all these aortic diseases by physicians and researchers. Due to the fact that the atherosclerotic regions are associated with complex blood flow patterns, it has believed that hemodynamics and fluid-structure interaction play important roles in regulating atherogenesis. As one of the most complex flow situations found in cardio- vascular system due to the strong curvature effects, irregular geometry, tapering and branching, and twisting, theoretical prediction and in vivo quantitative experimental data regarding to the complex blood flow dynamics are substantial paucity. In recent years, computational fluid dynamics (CFD) has emerged as a popular research tool to study the characteristics of aortic flow and aim to enhance the understanding of the underlying physics behind arteriosclerosis. In this research, we study the hemo- dynamics and flow-vessel interaction in patient specific normal (healthy) and dilated (diseased) aortas using Ansys-Fluent and Ansys-Workbench. The computation con- sists of three parts: segmentation of arterial geometry for the CFD simulation from computed tomography (CT) scanning data using MIMICS; finite volume simulation of hemodynamics of steady and pulsatile flow using Ansys-Fluent; an attempt to perform the Fluid Structure Simulation of the normal aorta using Ansys-Workbench. Instead of neglecting the branching or smoothing out the wall for simplification as a lot of similar computation in literature, we use the exact aortic geometry. Segmen- tation from real time CT images from two patients, one young and another old to represent healthy and diseased aorta respectively, is on MIMICS. The MIMICS seg- mentation operation includes: first cropping the required part of aorta from CT dicom data of the whole chest, masking of the aorta from coronal, axial and saggital views of the same to extract the exact 3D geometry of the aorta. Next step was to perform surface improvement using MIMICS 3-matic module to repair for holes, noise shells and overlapping triangles to create a good quality surface of the geometry. A hexahe- dral volume mesh was created in T-Grid. Since T-grid cannot recognize the geometry format created by MIMICS 3-matic; the required step geometry file was created in Pro-Engineer. After the meshing operation is performed, the mesh is exported to Ansys Fluent to perform the required fluid simulation imposing adequate boundary conditions accordingly. Two types of study are performed for hemodynamics. First is a steady flow driven by specified parabolic velocity at inlet. We captured the flow feature such as skewness of velocity around the aortic arch regions and vortices pairs, which are in good agreement with open data in literature. Second is a pulsatile flow. Two pulsatile velocity profiles are imposed at the inlet of healthy and diseased aorta respectively. The pulsatile analysis was accomplished for peak systolic, mid systolic and diastolic phase of the entire cardiac cycle. During peak systole and mid-systole, high WSS was found at the aortic branch roots and arch regions and diastole resulted in flow reversals and low WSS values due to small aortic inflow. In brief, areas of sudden geometry change, i.e. the branch roots and irregular surfaces of the geom- etry experience more WSS. Also it was found that dilated aorta has more sporadic nature of WSS in different regions than normal aorta which displays a more uniform WSS distribution all over the aorta surface. Fluid-Structure Interaction simulation is performed on Ansys-WorkBench through the coupling of fluid dynamics and solid mechanics. Focus is on the maximum displacement and equivalent stress to find out the future failure regions for the peak velocity of the cardiac cycle.

Indiana University-Purdue University Indianapolis (IUPUI) / Recent advancements in the management of systemic glucose regulation in obesity/T2DM include drug therapies designed to utilize components of the incretin system specifically related to glucagon-like peptide 1 (GLP-1). More recently, GLP-1 has been investigated for potential cardioprotective effects. Several investigations have revealed that acute/sub-acute intravenous administration of GLP-1 significantly reduces myocardial infarct size following ischemia/reperfusion injury and improves cardiac contractile function in the settings of coronary artery disease, myocardial ischemia/reperfusion injury, and heart failure. Despite an abundance of data indicating that intravenous infusion of GLP-1 is cardioprotective, information has been lacking on the cardiac effects of iv GLP-1 in the MetS or T2DM population. Some important questions this study aimed to address are 1) what are the direct, dose-dependent cardiac effects of GLP-1 in-vivo 2) are the cardiac effects influenced by cardiac demand (MVO2) and/or ischemia, 3) does GLP-1 effect myocardial blood flow, glucose uptake or total oxidative metabolism in human subjects, and 4) are the cardiac effects of GLP-1 treatment impaired in the settings of obesity/MetS and T2DM. Initial studies conducted in canines demonstrated that GLP-1 had no direct effect on coronary blood flow in-vivo or vasomotor tone in-vitro, but preferentially increased myocardial glucose uptake in ischemic myocardium independent of effects on cardiac contractile function or coronary blood flow. Parallel translational studies conducted in the humans and Ossabaw swine demonstrate that iv GLP-1 significantly increases myocardial glucose uptake at rest and in response to increases in cardiac demand (MVO2) in lean subjects, but not in the settings of obesity/MetS and T2DM. Further investigation in isolated cardiac tissue from lean and obese/MetS swine indicate that this impairment in GLP-1 responsiveness is related to attenuated activation of p38-MAPK, independent of alterations in GLP-1 receptor expression or PKA-dependent signaling. Our results indicate that the affects of GLP-1 to reduce cardiac damage and increase left ventricular performance may be impaired by obesity/MetS and T2DM.

Indiana University-Purdue University Indianapolis (IUPUI) / Peripheral arterial disease is caused by plaque buildup in the peripheral arteries. Standard treatments are available when the blockage is proximal and focal, however when distal and diffuse the same type of the treatment options are not beneficial due to the diseased locations. Restoration of blood flow and further salvaging of the limb in these patients can occur in a retrograde manner through the venous system, called retroperfusion or arteriovenous reversal. Retroperfusion has been explored over the last century, where early side to side artery to venous connections had issues with valve competency prohibiting distal flows, edema buildup, and heart failure. However, more recent clinical studies create a bypass to a foot vein to ensure distal flows, and though the results have been promising, it requires a lengthy invasive procedure. It is our belief that the concerns of both retroperfusion approaches can be overcome in a minimally invasive/catheter based approach in which the catheter is engineered to a specific resistance that avoids edema and the perfusion location allows for valves to be passable and flow to reach distally. In this approach, the pressure flow relations were characterized in the retroperfused venous system in ex-vivo canine legs to locate the optimal perfusion location followed by in-vivo validation of canines. Six canines were acutely injured for 1-3 hours by surgical ligation of the terminal aorta and both external iliac arteries. Retroperfusion was successfully performed on five of the dogs at the venous popliteal bifurcation for approximately one hour, where flow rates at peak pressures reached near half of forward flow (37±3 vs. 84±27ml/min) and from which the slope of the P/F curves displayed a retro venous vasculature resistance that was used to calculate the optimal catheter resistance. To assess differences in regional perfusion, microspheres were passed during retroperfusion and compared to baseline microspheres passed arterially prior to occlusion in which the ratio of retroperfusion and forward perfusion levels were near the ratio of reversed and forward venous flow (0.44) throughout the limb. Decreases in critical metabolites during injury trended towards normal levels post-retroperfusion. By identifying the popliteal bifurication as a perfusion site to restore blood flow in the entirety of the distal ischemic limb, showing reversal of injury, and knowing what catheter resistances to target for further chronic studies, steps towards controlled retroperfusion and thus more efficient treatment options can be made for severe PAD patients.