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Item 3D simulation of a viscous flow past a compliant model of arteriovenous-graft annastomosis(Elsevier, 2019-03) Bai, Zengding; Zhu, Luoding; Mathematical Sciences, School of ScienceHemodialysis is a common treatment for end-stage renal-disease patients to manage their renal failure while awaiting kidney transplant. Arteriovenous graft (AVG) is a major vascular access for hemodialysis but often fails due to the thrombosis near the vein-graft anastomosis. Almost all of the existing computational studies involving AVG assume that the vein and graft are rigid. As a first step to include vein/graft flexibility, we consider an ideal vein-AVG anastomosis model and apply the lattice Boltzmann-immersed boundary (LB-IB) framework for fluid-structure-interaction. The framework is extended to the case of non-uniform Lagrangian mesh for complex structure. After verification and validation of the numerical method and its implementation, many simulations are performed to simulate a viscous incompressible flow past the anastomosis model under pulsatile flow condition using various levels of vein elasticity. Our simulation results indicate that vein compliance may lessen flow disturbance and a more compliant vein experiences less wall shear stress (WSS).Item Blood circulation and aqueous humor flow in the eye : multi-scale modeling and clinical applications(2016-06-14) Cassani, Simone; Guidoboni, Giovanna; Arciero, Julia Concetta; Harris, AlonGlaucoma is a multi-factorial ocular disease associated with death of retinal ganglion cells and irreversible vision loss. Many risk factors contribute to glaucomatous damage, including elevated intraocular pressure (IOP), age, genetics, and other diseases such as diabetes and systemic hypertension. Interestingly, alterations in retinal hemodynamics have also been associated with glaucoma. A better understanding of the factors that contribute to these hemodynamic alterations could lead to improved and more appropriate clinical approaches to manage and hopefully treat glaucoma patients. In this thesis, we develop several mathematical models aimed at describing ocular hemodynamics and oxygenation in health and disease. Precisely we describe: (i) a time-dependent mathematical model for the retinal circulation that includes macrocirculation, microcirculation, phenomenological vascular regulation, and the mechanical effect of IOP on the retinal vasculature; (ii) a steady-state mathematical model for the retinal circulation that includes macrocirculation, microcirculation, mechanistic vascular regulation, the effect of IOP on the central retinal artery and central retinal vein, and the transport of oxygen in the retinal tissue using a Krogh cylinder type model; (iii) a steady-state mathematical model for the transport of oxygen in the retinal microcirculation and tissue based on a realistic retinal anatomy; and (iv) a steady-state mathematical model for the production and drainage of aqueous humor (AH). The main objective of this work is to study the relationship between IOP, systemic blood pressure, and the functionality of vascular autoregulation; the transport and exchange of oxygen in the retinal vasculature and tissue; and the production and drainage of AH, that contributes to the level of IOP. The models developed in this thesis predict that (i) the autoregulation plateau occurs for different values of IOP in hypertensive and normotensive patients. Thus, the level of blood pressure and functionality of autoregulation affect the changes in retinal hemodynamics caused by IOP and might explain the inconsistent outcomes of clinical studies; (ii) the metabolic and carbon dioxide mechanisms play a major role in the vascular regulation of the retina. Thus, the impairment of either of these mechanisms could cause ischemic damage to the retinal tissue; (iii) the multi-layer description of transport of oxygen in the retinal tissue accounts for the effect of the inner and outer retina, thereby improving the predictive ability of the model; (iv) a greater reduction in IOP is obtained if topical medications target AH production rather that AH drainage and if IOP-lowering medications are administrated to patients that exhibit a high initial level of IOP. Thus, the effectiveness of IOP-lowering medications depend on a patient’s value of IOP. In conclusion, the results of this thesis demonstrate that the insight provided by mathematical modeling alongside clinical studies can improve the understanding of diseases and potentially contribute to the clinical development of new treatments.Item Change in arteriole diameter of retina with visual simulation(Office of the Vice Chancellor for Research, 2016-04-08) Tellapragada, Neelima; Burns, Steven; De Castro Arribas, Alberto; Sawides, Lucie; Othman, HindNeural activity and blood flow in the brain are tightly coupled. This coupling allows the brain to respond to periods of increased neural activity with increased blood flow. This coupling is known as neurovascular coupling. Many vascular based imaging techniques such as Functional MRI scans provide maps of signals of brain activity but they are limited by the resolution of fMRI to a few mm. The fMRI signal is indirect because the scanner is not tracking the neural activity directly but are measuring the changes in the blood oxygen levels. Since the retina and optic tract are part of the central nerves system and they can be measured optically it should be possible to make precise measurements of the retinal vasculature of the human retina and its response to changing stimulation levels. In this study we used an adaptive optics scanning laser ophthalmoscope (AOSLO) with multiply scattered light to measure the change in arteriolar diameter when the retina was stimulated with flickering light. We hypothesized that we could use this technique to measure both arterial dilation and time course. We used information from the reflectance of the vessel to Change in arteriole diameter of retina with visual simulation measure total vessel diameter. Images were acquired at approximately 30 Hz and averaged over 3.3 second periods. Retinal arteries were measured in five observers before, during, and after presentation of a large flickering stimulus. There was a 6-10% dilation of the blood vessels during the flicker. The Vascular dilation occurred within seconds of flickering onset and constricted again following the end of flicker stimulation. This work shows that with modern retinal imaging methods it is possible to make precise measures of vascular constriction and its time course in response to changing tissue demand.Item Contribution of K+ Channels to Coronary Dysfunction in Metabolic Syndrome(2009-06-24T12:58:39Z) Watanabe, Reina; Tune, Johnathan D.Coronary microvascular function is markedly impaired by the onset of the metabolic syndrome and may be an important contributor to the increased cardiovascular events associated with this mutlifactorial disorder. Despite increasing appreciation for the role of coronary K+ channels in regulation of coronary microvascular function, the contribution of K+ channels to the deleterious influence of metabolic syndrome has not been determined. Accordingly, the overall goal of this investigation was to delineate the mechanistic contribution of K+ channels to coronary microvascular dysfunction in metabolic syndrome. Experiments were performed on Ossabaw miniature swine fed a normal maintenance diet or an excess calorie atherogenic diet that induces the classical clinical features of metabolic syndrome including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and atherosclerosis. Experiments involved in vivo studies of coronary blood flow in open-chest anesthetized swine as well as conscious, chronically instrumented swine and in vitro studies in isolated coronary arteries, arterioles, and vascular smooth muscle cells. We found that coronary microvascular dysfunction in the metabolic syndrome significantly impairs coronary vasodilation in response to metabolic as well as ischemic stimuli. This impairment was directly related to decreased membrane trafficking and functional expression of BKCa channels in vascular smooth muscle cells that was accompanied by augmented L-type Ca2+ channel activity and increased intracellular Ca2+ concentration. In addition, we discovered that impairment of coronary vasodilation in the metabolic syndrome is mediated by reductions in the functional contribution of voltage-dependent K+ channels to the dilator response. Taken together, findings from this investigation demonstrate that the metabolic syndrome markedly attenuates coronary microvascular function via the diminished contribution of K+ channels to the overall control of coronary blood flow. Our data implicate impaired functional expression of coronary K+ channels as a critical mechanism underlying the increased incidence of cardiac arrhythmias, infarction and sudden cardiac death in obese patients with the metabolic syndrome.Item Experimental Measurement of Blood Pressure in 3-D Printed Human Vessels(2022-05) Talamantes, John, Jr.; Yu, Huidan (Whitney); Chen, Jie; Zhu, LikunA pulsatile flow loop can be suitable for measurement of in vitro blood pressure. The pressure data collected from such a system can be used for evaluating stenosis in human arteries, a condition in which the arterial lumen size is reduced. The objective of this work is to develop an experimental system to simulate blood flow in the human arterial system. This system will measure the in vitro hemodynamics using 3-D prints of vessels extracted from patient CT images. Images are segmented and processed to produce 3-D prints of vessel geometry, which are mounted in the loop. Control of flow and pressure is made possible by the use of components such as a pulsatile heart pump, resistance, and compliance elements. Output data is evaluated by comparison with CFD and invasive measurement. The system is capable of measurement of the pressures such as proximal, Pa, and distal, Pd, pressures to evaluate in vivo conditions and to assess the severity of stenosis. This is determined by use of parameters such as fractional flow reserve (FFR=Pd/Pa) or trans-stenotic pressure gradient (TSPG=Pa-Pd). This can be done on a non-invasive, patient specific basis, to avoid the risk and high cost of invasive measurement. In its operation, the preliminary measurement of blood pressures demonstrates agreement with the invasive measurement as well as the CFD results. These preliminary results are encouraging and can be improved upon by continuing development of the experimental system. A working pulsatile loop has been reached, an initial step taken for continued development. This loop is capable of measuring the flow and pressure from in a 3-D printed artery. Future works will include more life-like material for the artery prints, as well as cadaver vessels.Item The isolation and culture of endothelial colony forming cells from human and rat lungs(Nature, 2015-11) Alphonse, Rajesh S.; Vadivel, Arul; Zhong, Shumei; McConaghy, Suzanne; Ohls, Robin; Yoder, Mervin C.; Thébaud, Bernard; Department of Pediatrics, IU School of MedicineBlood vessels are crucial for the normal development, lifelong repair and homeostasis of tissues. Recently, vascular progenitor cell–driven 'postnatal vasculogenesis' has been suggested as an important mechanism that contributes to new blood vessel formation and organ repair. Among several described progenitor cell types that contribute to blood vessel formation, endothelial colony-forming cells (ECFCs) have received widespread attention as lineage-specific 'true' vascular progenitors. Here we describe a protocol for the isolation of pulmonary microvascular ECFCs from human and rat lung tissue. Our technique takes advantage of an earlier protocol for the isolation of circulating ECFCs from the mononuclear cellular fraction of peripheral blood. We adapted the earlier protocol to isolate resident ECFCs from the distal lung tissue. After enzymatic dispersion of rat or human lung samples into a cellular suspension, CD31-expressing cells are positively selected using magnetic-activated cell sorting and plated in endothelial-specific growth conditions. The colonies arising after 1–2 weeks in culture are carefully separated and expanded to yield pure ECFC cultures after a further 2–3 weeks. The resulting cells demonstrate the defining characteristics of ECFCs such as (i) 'cobblestone' morphology of cultured cell monolayers; (ii) acetylated low-density lipoprotein uptake and Ulex europaeus lectin binding; (iii) tube-like network formation in Matrigel; (iv) expression of endothelial cell–specific surface markers and the absence of hematopoietic or myeloid surface antigens; (v) self-renewal potential displayed by the most proliferative cells; and (vi) contribution to de novo vessel formation in an in vivo mouse implant model. Assuming typical initial cell adhesion and proliferation rates, the entire procedure can be completed within 4 weeks. Isolation and culture of lung vascular ECFCs will allow assessment of the functional state of these cells in experimental and human lung diseases, providing newer insights into their pathophysiological mechanisms.Item Mathematical methods for modeling the microcirculation(AIMS, 2017) Arciero, Julia C.; Causin, Paola; Malgaroli, Francesca; Mathematical Sciences, School of ScienceThe microcirculation plays a major role in maintaining homeostasis in the body. Alterations or dysfunctions of the microcirculation can lead to several types of serious diseases. It is not surprising, then, that the microcirculation has been an object of intense theoretical and experimental study over the past few decades. Mathematical approaches offer a valuable method for quantifying the relationships between various mechanical, hemodynamic, and regulatory factors of the microcirculation and the pathophysiology of numerous diseases. This work provides an overview of several mathematical models that describe and investigate the many different aspects of the microcirculation, including geometry of the vascular bed, blood flow in the vascular networks, solute transport and delivery to the surrounding tissue, and vessel wall mechanics under passive and active stimuli. Representing relevant phenomena across multiple spatial scales remains a major challenge in modeling the microcirculation. Nevertheless, the depth and breadth of mathematical modeling with applications in the microcirculation is demonstrated in this work. A special emphasis is placed on models of the retinal circulation, including models that predict the influence of ocular hemodynamic alterations with the progression of ocular diseases such as glaucoma.Item Thermotherapy reduces blood pressure and circulating endothelin-1 concentration and enhances leg blood flow in patients with symptomatic peripheral artery disease(APS Journals, 2016-08-01) Neff, Dustin; Kuhlenhoelter, Alisha M.; Lin, Chen; Wong, Brett J.; Motaganahalli, Raghu L.; Roseguini, Bruno T.; Radiology and Imaging Sciences, School of MedicineLeg thermotherapy (TT) application reduces blood pressure (BP) and increases both limb blood flow and circulating levels of anti-inflammatory mediators in healthy, young humans and animals. The purpose of the present study was to determine the impact of TT application using a water-circulating garment on leg and systemic hemodynamics and on the concentrations of circulating cytokines and vasoactive mediators in patients with symptomatic peripheral artery disease (PAD). Sixteen patients with PAD and intermittent claudication (age: 63 ± 9 yr) completed three experimental sessions in a randomized order: TT, control intervention, and one exercise testing session. The garment was perfused with 48°C water for 90 min in the TT session and with 33°C water in the control intervention. A subset of 10 patients also underwent a protocol for the measurement of blood flow in the popliteal artery during 90 min of TT using phase-contrast MRI. Compared with the control intervention, TT promoted a significant reduction in systolic (∼11 mmHg) and diastolic (∼6 mmHg) BP (P < 0.05) that persisted for nearly 2 h after the end of the treatment. The serum concentration of endothelin-1 (ET-1) was significantly lower 30 min after exposure to TT (Control: 2.3 ± 0.1 vs. TT: 1.9 ± 0.09 pg/ml, P = 0.026). In addition, TT induced a marked increase in peak blood flow velocity (∼68%), average velocity (∼76%), and average blood flow (∼102%) in the popliteal artery (P < 0.01). These findings indicate that TT is a practical and effective strategy to reduce BP and circulating ET-1 concentration and enhance leg blood flow in patients with PAD.Item VOLUMETRIC LATTICE BOLTZMANN SIMULATION FOR BLOOD FLOW IN AORTA ARTERY PUMPED THROUGH AORTIC HEART VALVE(Office of the Vice Chancellor for Research, 2012-04-13) Deep, Debanjan; Yu, HuidanComplicated moving boundaries pose a major challenge in compu-tational fluid dynamics for complex flows, especially in the biomechan-ics of both blood flow in the cardiovascular system and air flow in the respiratory system where the compliant nature of the vessels can have significant effects on the flow rate and wall shear stress. We develop an innovative approach to treat arbitrarily moving boundaries in Lat-tice Boltzmann Method (LBM) using a volumetric lattice Boltzmann representation, which distributes particles in fluid lattice cells. A volu-metric bounce-back procedure is applied in the streaming step while momentum exchange between the fluid and moving solid boundary are accounted for in the collision step. Additional boundary-induced migra-tion is introduced to conserve fluid mass as the boundary moves across fluid cells. We use the volumetric LBM to simulate blood flow in aorta pumped from heart focusing on the flow rate, flow structure, pressure distribution within the aorta for different heart pumping con-ditions. For validation, the volumetric LBM is compared with Navier-Stokes computation and good agreements are achieved. We study the flow dynamics within the aorta in the cardiac cycle (systole and diasto-le) through alternatively opening and closing the inlet boundary to mimic the heart pumping mechanism.