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In Vitro and In Silico Study of Hemodynamics In Vascular Models: Validating Computational Fluid Dynamics for Medical Application

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This study investigates the application of Computational Fluid Dynamics (CFD) to the medical field. An overview of recent advances in computational simulation and modeling in medical applications is provided, with a particular emphasis on CFD. This study attempts to validate

This study investigates the application of Computational Fluid Dynamics (CFD) to the medical field. An overview of recent advances in computational simulation and modeling in medical applications is provided, with a particular emphasis on CFD. This study attempts to validate CFD and demonstrate the possibility for applying CFD to the clinical treatment and evaluation of atherosclerotic disease. Three different geometric configurations are investigated: one idealized bifurcation with a primary diameter of 8 mm, and two different patient-specific models of the bifurcation from the common femoral artery to the superficial and deep femoral arteries. CFD is compared against experimental measurements of steady state and pulsatile flow acquired with Particle Image Velocimetry (PIV). Steady state and pulsatile flow rates that are consistent with those observed in the femoral artery are used. In addition, pulsatile CFD simulations are analyzed in order to demonstrate meaningful clinical applications for studying and evaluating the treatment of atherosclerotic disease. CFD was successfully validated for steady state flow, with an average percent error of 6.991%. Potential for validation was also demonstrated for pulsatile flow, but methodological errors warrant further investigation to reformulate methods and analyze results. Quantities frequently associated with atherosclerotic disease and arterial bifurcations, such as large variations in wall shear stress and the presence of recirculation zones are demonstrated from the pulsatile CFD simulations. Further study is required in order to evaluate whether or not such phenomena are represented by CFD accurately. Further study must also be performed in order to evaluate the practicality and utility of CFD for the evaluation of atherosclerotic disease treatment.

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2016-05

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PIV ANALYSIS OF BASILAR TIP ANEURYSM HEMODYNAMICS, AND THE EFFECTS OF ENTERPRISE STENT TREATMENT

Description

Intracranial aneurysms, which form in the blood vessels of the brain, are particularly dangerous because of the importance and fragility of the human brain. When an intracranial aneurysm gets large it poses a significant risk of bursting and causing subarachnoid

Intracranial aneurysms, which form in the blood vessels of the brain, are particularly dangerous because of the importance and fragility of the human brain. When an intracranial aneurysm gets large it poses a significant risk of bursting and causing subarachnoid hemorrhaging (SAH), a possibly fatal condition. One possible treatment involves placing a stent in the vessel to act as a flow diverter. In this study we look at the hemodynamics of two geometries of idealized basilar tip aneurysms, at 2,3, and 4 ml/s pulsatile flow, at three different points in the cardiac cycle. The smaller model had neck and dome diameters of 2.67 mm and 4 mm respectively, while the larger aneurysm had neck and dome diameters of 3 mm and 6 mm respectively. Both diameters and the dome to neck ratio increased in the second model, representing growth over time. Flow was analyzed using stereoscopic particle image velocimetry (PIV) for both geometries in untreated models, as well as after treatment with a high porosity Enterprise stent (Codman and Shurtleff Inc.). Flow in the models was characterized by root mean square velocity in the aneurysm and neck plane, cross neck flow, max aneurysm vorticity, and total aneurysm kinetic energy. It was found that in the smaller aneurysm model (model 1), Enterprise stent treatment reduced all flow parameters substantially. The smallest reduction was in max vorticity, at 42.48%, and the largest in total kinetic energy, at 75.69%. In the larger model (model 2) there was a 52.18% reduction in cross neck flow, but a 167.28% increase in aneurysm vorticity. The other three parameters experienced little change. These results, along with observed velocity vector fields, indicate a noticeable diversion of flow away from the aneurysm in the stent treated model 1. Treatment in model 2 had a small flow diversion effect, but also altered flow in unpredictable ways, in some cases having a detrimental effect on aneurysm hemodynamics. The results of this study indicate that Enterprise stent treatment is only effective in small, relatively undeveloped aneurysm geometries, and waiting until an aneurysm has grown too large can eliminate this treatment option altogether.

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2013-05

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Particle image segmentation based on Bhattacharyya distance

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Image segmentation is of great importance and value in many applications. In computer vision, image segmentation is the tool and process of locating objects and boundaries within images. The segmentation result may provide more meaningful image data. Generally, there are

Image segmentation is of great importance and value in many applications. In computer vision, image segmentation is the tool and process of locating objects and boundaries within images. The segmentation result may provide more meaningful image data. Generally, there are two fundamental image segmentation algorithms: discontinuity and similarity. The idea behind discontinuity is locating the abrupt changes in intensity of images, as are often seen in edges or boundaries. Similarity subdivides an image into regions that fit the pre-defined criteria. The algorithm utilized in this thesis is the second category.

This study addresses the problem of particle image segmentation by measuring the similarity between a sampled region and an adjacent region, based on Bhattacharyya distance and an image feature extraction technique that uses distribution of local binary patterns and pattern contrasts. A boundary smoothing process is developed to improve the accuracy of the segmentation. The novel particle image segmentation algorithm is tested using four different cases of particle image velocimetry (PIV) images. The obtained experimental results of segmentations provide partitioning of the objects within 10 percent error rate. Ground-truth segmentation data, which are manually segmented image from each case, are used to calculate the error rate of the segmentations.

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2015

Optimizing micro-vortex chamber for living single cell rotation

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Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study

Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system can be used to diagnose fatal diseases, such as cancer, at an early stage. One proven method, CellCT, accomplishes 3D imaging by rotating a single cell around a fixed axis. However, some existing cell rotating mechanisms require either intricate microfabrication, and some fail to provide a suitable environment for living cells. This thesis develops a microvorterx chamber that allows living cells to be rotated by hydrodynamic alone while facilitating imaging access. In this thesis work, 1) the new chamber design was developed through numerical simulation. Simulations revealed that in order to form a microvortex in the side chamber, the ratio of the chamber opening to the channel width must be smaller than one. After comparing different chamber designs, the trapezoidal side chamber was selected because it demonstrated controllable circulation and met the imaging requirements. Microvortex properties were not sensitive to the chambers with interface angles ranging from 0.32 to 0.64. A similar trend was observed when chamber heights were larger than chamber opening. 2) Micro-particle image velocimetry was used to characterize microvortices and validate simulation results. Agreement between experimentation and simulation confirmed that numerical simulation was an effective method for chamber design. 3) Finally, cell rotation experiments were performed in the trapezoidal side chamber. The experimental results demonstrated cell rotational rates ranging from 12 to 29 rpm for regular cells. With a volumetric flow rate of 0.5 µL/s, an irregular cell rotated at a mean rate of 97 ± 3 rpm. Rotational rates can be changed by altering inlet flow rates.

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2011

Volumetric particle velocimetry for microscale flows

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Microfluidics is the study of fluid flow at very small scales (micro -- one millionth of a meter) and is prevalent in many areas of science and engineering. Typical applications include lab-on-a-chip devices, microfluidic fuel cells, and DNA separation technologies.

Microfluidics is the study of fluid flow at very small scales (micro -- one millionth of a meter) and is prevalent in many areas of science and engineering. Typical applications include lab-on-a-chip devices, microfluidic fuel cells, and DNA separation technologies. Many of these microfluidic devices rely on micron-resolution velocimetry measurements to improve microchannel design and characterize existing devices. Methods such as micro particle imaging velocimetry (microPIV) and micro particle tracking velocimetry (microPTV) are mature and established methods for characterization of steady 2D flow fields. Increasingly complex microdevices require techniques that measure unsteady and/or three dimensional velocity fields. This dissertation presents a method for three-dimensional velocimetry of unsteady microflows based on spinning disk confocal microscopy and depth scanning of a microvolume. High-speed 2D unsteady velocity fields are resolved by acquiring images of particle motion using a high-speed CMOS camera and confocal microscope. The confocal microscope spatially filters out of focus light using a rotating disk of pinholes placed in the imaging path, improving the ability of the system to resolve unsteady microPIV measurements by improving the image and correlation signal to noise ratio. For 3D3C measurements, a piezo-actuated objective positioner quickly scans the depth of the microvolume and collects 2D image slices, which are stacked into 3D images. Super resolution microPIV interrogates these 3D images using microPIV as a predictor field for tracking individual particles with microPTV. The 3D3C diagnostic is demonstrated by measuring a pressure driven flow in a three-dimensional expanding microchannel. The experimental velocimetry data acquired at 30 Hz with instantaneous spatial resolution of 4.5 by 4.5 by 4.5 microns agrees well with a computational model of the flow field. The technique allows for isosurface visualization of time resolved 3D3C particle motion and high spatial resolution velocity measurements without requiring a calibration step or reconstruction algorithms. Several applications are investigated, including 3D quantitative fluorescence imaging of isotachophoresis plugs advecting through a microchannel and the dynamics of reaction induced colloidal crystal deposition.

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2011

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Modeling cardiac function with particle image velocimetry

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The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses

The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses on the application of particle image velocimetry (PIV) to the study of intracardiac hemodynamics. This is accomplished primarily though the use of ultrasound based PIV, which allows for in vivo visualization of intracardiac flow without the requirement for optical access, as is required with traditional camera-based PIV methods.

The fundamentals of ultrasound PIV are introduced, including experimental methods for its implementation as well as a discussion on estimating and mitigating measurement error. Ultrasound PIV is then compared to optical PIV; this is a highly developed technique with proven accuracy; through rigorous examination it has become the “gold standard” of two-dimensional flow visualization. Results show good agreement between the two methods.

Using a mechanical left heart model, a multi-plane ultrasound PIV technique is introduced and applied to quantify a complex, three-dimensional flow that is analogous to the left intraventricular flow. Changes in ventricular flow dynamics due to the rotational orientation of mechanical heart valves are studied; the results demonstrate the importance of multi-plane imaging techniques when trying to assess the strongly three-dimensional intraventricular flow.

The potential use of ultrasound PIV as an early diagnosis technique is demonstrated through the development of a novel elasticity estimation technique. A finite element analysis routine is couple with an ensemble Kalman filter to allow for the estimation of material elasticity using forcing and displacement data derived from PIV. Results demonstrate that it is possible to estimate elasticity using forcing data derived from a PIV vector field, provided vector density is sufficient.

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2015

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Experimental study of the flow field in a model rotor-stator disk cavity using particle image velocimetry

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Modern day gas turbine designers face the problem of hot mainstream gas ingestion into rotor-stator disk cavities. To counter this ingestion, seals are installed on the rotor and stator disk rims and purge air, bled off from the compressor, is

Modern day gas turbine designers face the problem of hot mainstream gas ingestion into rotor-stator disk cavities. To counter this ingestion, seals are installed on the rotor and stator disk rims and purge air, bled off from the compressor, is injected into the cavities. It is desirable to reduce the supply of purge air as this decreases the net power output as well as efficiency of the gas turbine. Since the purge air influences the disk cavity flow field and effectively the amount of ingestion, the aim of this work was to study the cavity velocity field experimentally using Particle Image Velocimetry (PIV). Experiments were carried out in a model single-stage axial flow turbine set-up that featured blades as well as vanes, with purge air supplied at the hub of the rotor-stator disk cavity. Along with the rotor and stator rim seals, an inner labyrinth seal was provided which split the disk cavity into a rim cavity and an inner cavity. First, static gage pressure distribution was measured to ensure that nominally steady flow conditions had been achieved. The PIV experiments were then performed to map the velocity field on the radial-tangential plane within the rim cavity at four axial locations. Instantaneous velocity maps obtained by PIV were analyzed sector-by-sector to understand the rim cavity flow field. It was observed that the tangential velocity dominated the cavity flow at low purge air flow rate, its dominance decreasing with increase in the purge air flow rate. Radially inboard of the rim cavity, negative radial velocity near the stator surface and positive radial velocity near the rotor surface indicated the presence of a recirculation region in the cavity whose radial extent increased with increase in the purge air flow rate. Qualitative flow streamline patterns are plotted within the rim cavity for different experimental conditions by combining the PIV map information with ingestion measurements within the cavity as reported in Thiagarajan (2013).

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2013

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Characterization of the effects of cerebral aneurysm geometry on hemodynamics and endovascular treatment outcomes

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Cerebral aneurysms are pathological balloonings of blood vessels in the brain, commonly found in the arterial network at the base of the brain. Cerebral aneurysm rupture can lead to a dangerous medical condition, subarachnoid hemorrhage, that is associated with high

Cerebral aneurysms are pathological balloonings of blood vessels in the brain, commonly found in the arterial network at the base of the brain. Cerebral aneurysm rupture can lead to a dangerous medical condition, subarachnoid hemorrhage, that is associated with high rates of morbidity and mortality. Effective evaluation and management of cerebral aneurysms is therefore essential to public health. The goal of treating an aneurysm is to isolate the aneurysm from its surrounding circulation, thereby preventing further growth and rupture. Endovascular treatment for cerebral aneurysms has gained popularity over traditional surgical techniques due to its minimally invasive nature and shorter associated recovery time. The hemodynamic modifications that the treatment effects can promote thrombus formation within the aneurysm leading to eventual isolation. However, different treatment devices can effect very different hemodynamic outcomes in aneurysms with different geometries.

Currently, cerebral aneurysm risk evaluation and treatment planning in clinical practice is largely based on geometric features of the aneurysm including the dome size, dome-to-neck ratio, and parent vessel geometry. Hemodynamics, on the other hand, although known to be deeply involved in cerebral aneurysm initiation and progression, are considered to a lesser degree. Previous work in the field of biofluid mechanics has demonstrated that geometry is a driving factor behind aneurysmal hemodynamics.

The goal of this research is to develop a more combined geometric/hemodynamic basis for informing clinical decisions. Geometric main effects were analyzed to quantify contributions made by geometric factors that describe cerebral aneurysms (i.e., dome size, dome-to-neck ratio, and inflow angle) to clinically relevant hemodynamic responses (i.e., wall shear stress, root mean square velocity magnitude and cross-neck flow). Computational templates of idealized bifurcation and sidewall aneurysms were created to satisfy a two-level full factorial design, and examined using computational fluid dynamics. A subset of the computational bifurcation templates was also translated into physical models for experimental validation using particle image velocimetry. The effects of geometry on treatment were analyzed by virtually treating the aneurysm templates with endovascular devices. The statistical relationships between geometry, treatment, and flow that emerged have the potential to play a valuable role in clinical practice.

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2016

Fundamentals and Applications of N-pulse Particle Image Velocimetry-accelerometry: Towards Advanced Measurements of Complex Flows and Turbulence

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Over the past three decades, particle image velocimetry (PIV) has been continuously growing to become an informative and robust experimental tool for fluid mechanics research. Compared to the early stage of PIV development, the dynamic range of PIV has been

Over the past three decades, particle image velocimetry (PIV) has been continuously growing to become an informative and robust experimental tool for fluid mechanics research. Compared to the early stage of PIV development, the dynamic range of PIV has been improved by about an order of magnitude (Adrian, 2005; Westerweel et al., 2013). Further improvement requires a breakthrough innovation, which constitutes the main motivation of this dissertation. N-pulse particle image velocimetry-accelerometry (N-pulse PIVA, where N>=3) is a promising technique to this regard. It employs bursts of N pulses to gain advantages in both spatial and temporal resolution. The performance improvement by N-pulse PIVA is studied using particle tracking (i.e. N-pulse PTVA), and it is shown that an enhancement of at least another order of magnitude is achievable. Furthermore, the capability of N-pulse PIVA to measure unsteady acceleration and force is demonstrated in the context of an oscillating cylinder interacting with surrounding fluid. The cylinder motion, the fluid velocity and acceleration, and the fluid force exerted on the cylinder are successfully measured. On the other hand, a key issue of multi-camera registration for the implementation of N-pulse PIVA is addressed with an accuracy of 0.001 pixel. Subsequently, two applications of N-pulse PTVA to complex flows and turbulence are presented. A novel 8-pulse PTVA analysis was developed and validated to accurately resolve particle unsteady drag in post-shock flows. It is found that the particle drag is substantially elevated from the standard drag due to flow unsteadiness, and a new drag correlation incorporating particle Reynolds number and unsteadiness is desired upon removal of the uncertainty arising from non-uniform particle size. Next, the estimation of turbulence statistics utilizes the ensemble average of 4-pulse PTV data within a small domain of an optimally determined size. The estimation of mean velocity, mean velocity gradient and isotropic dissipation rate are presented and discussed by means of synthetic turbulence, as well as a tomographic measurement of turbulent boundary layer. The results indicate the superior capability of the N-pulse PTV based method to extract high-spatial-resolution high-accuracy turbulence statistics.

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2018

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Improved techniques for cardiovascular flow experiments

Description

Aortic pathologies such as coarctation, dissection, and aneurysm represent a

particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these

Aortic pathologies such as coarctation, dissection, and aneurysm represent a

particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies and for planning their surgical repair. In vitro experiments are required to validate these simulations against real world data, and a pulsatile flow pump system can provide physiologic flow conditions characteristic of the aorta.

This dissertation presents improved experimental techniques for in vitro aortic blood flow and the increasingly larger parts of the human cardiovascular system. Specifically, this work develops new flow management and measurement techniques for cardiovascular flow experiments with the aim to improve clinical evaluation and treatment planning of aortic diseases.

The hypothesis of this research is that transient flow driven by a step change in volume flux in a piston-based pulsatile flow pump system behaves differently from transient flow driven by a step change in pressure gradient, the development time being substantially reduced in the former. Due to this difference in behavior, the response to a piston-driven pump can be predicted in order to establish inlet velocity and flow waveforms at a downstream phantom model.

The main objectives of this dissertation were: 1) to design, construct, and validate a piston-based flow pump system for aortic flow experiments, 2) to characterize temporal and spatial development of start-up flows driven by a piston pump that produces a step change from zero flow to a constant volume flux in realistic (finite) tube geometries for physiologic Reynolds numbers, and 3) to develop a method to predict downstream velocity and flow waveforms at the inlet of an aortic phantom model and determine the input waveform needed to achieve the intended waveform at the test section. Application of these newly improved flow management tools and measurement techniques were then demonstrated through in vitro experiments in patient-specific coarctation of aorta flow phantom models manufactured in-house and compared to computational simulations to inform and execute future experiments and simulations.

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2015