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Description
Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery is performed to visualize and quantify the time resolved distribution of MRI contrast agents. I find it is possible to visualize contrast agent distributions in near real time from local delivery vehicles using MRI. Three dimensional T1 maps are processed to produce in vivo concentration maps of contrast agent for individual animal models. The method for obtaining concentration maps is analyzed to estimate errors introduced at various steps in the process. The method is used to evaluate different controlled release vehicles, vehicle placement, and type of surgical wound in rabbits as a model for antimicrobial delivery to orthopaedic infection sites. I are able to see differences between all these factors; however, all images show that contrast agent remains fairly local to the wound site and do not distribute to tissues far from the implant in therapeutic concentrations. I also produce a mathematical model that investigates important mechanisms in the transport of antimicrobials in a wound environment. It is determined from both the images and the mathematical model that antimicrobial distribution in an orthopaedic wounds is dependent on both diffusive and convective mechanisms. Furthermore, I began development of MRI visible therapeutic agents to examine active drug distributions. I hypothesize that this work can be developed into a non-invasive, patient specific, clinical tool to evaluate the success of interventional procedures using local drug delivery vehicles.
ContributorsGiers, Morgan (Author) / Caplan, Michael R (Thesis advisor) / Massia, Stephen P (Committee member) / Frakes, David (Committee member) / McLaren, Alex C. (Committee member) / Vernon, Brent L (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013
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Description
A cerebral aneurysm is a bulging of a blood vessel in the brain. Aneurysmal rupture affects 25,000 people each year and is associated with a 45% mortality rate. Therefore, it is critically important to treat cerebral aneurysms effectively before they rupture. Endovascular coiling is the most effective treatment for cerebral

A cerebral aneurysm is a bulging of a blood vessel in the brain. Aneurysmal rupture affects 25,000 people each year and is associated with a 45% mortality rate. Therefore, it is critically important to treat cerebral aneurysms effectively before they rupture. Endovascular coiling is the most effective treatment for cerebral aneurysms. During coiling process, series of metallic coils are deployed into the aneurysmal sack with the intent of reaching a sufficient packing density (PD). Coils packing can facilitate thrombus formation and help seal off the aneurysm from circulation over time. While coiling is effective, high rates of treatment failure have been associated with basilar tip aneurysms (BTAs). Treatment failure may be related to geometrical features of the aneurysm. The purpose of this study was to investigate the influence of dome size, parent vessel (PV) angle, and PD on post-treatment aneurysmal hemodynamics using both computational fluid dynamics (CFD) and particle image velocimetry (PIV). Flows in four idealized BTA models with a combination of dome sizes and two different PV angles were simulated using CFD and then validated against PIV data. Percent reductions in post-treatment aneurysmal velocity and cross-neck (CN) flow as well as percent coverage of low wall shear stress (WSS) area were analyzed. In all models, aneurysmal velocity and CN flow decreased after coiling, while low WSS area increased. However, with increasing PD, further reductions were observed in aneurysmal velocity and CN flow, but minimal changes were observed in low WSS area. Overall, coil PD had the greatest impact while dome size has greater impact than PV angle on aneurysmal hemodynamics. These findings lead to a conclusion that combinations of treatment goals and geometric factor may play key roles in coil embolization treatment outcomes, and support that different treatment timing may be a critical factor in treatment optimization.
ContributorsIndahlastari, Aprinda (Author) / Frakes, David (Thesis advisor) / Chong, Brian (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to support future improvements in scan time and resolution. SNR efficiency is improved by sampling data for a larger proportion of

Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to support future improvements in scan time and resolution. SNR efficiency is improved by sampling data for a larger proportion of total imaging time. This is challenging as these acquisitions are typically subject to artifacts such as blurring and distortions. The current work proposes a set of tools to help with the creation of different types of SNR efficient scans. An SNR efficient pulse sequence providing diffusion imaging data with full brain coverage and minimal distortion is first introduced. The proposed method acquires single-shot, low resolution image slabs which are then combined to reconstruct the full volume. An iterative deblurring algorithm allowing the lengthening of spiral SPoiled GRadient echo (SPGR) acquisition windows in the presence of rapidly varying off-resonance fields is then presented. Finally, an efficient and practical way of collecting 3D reformatted data is proposed. This method constitutes a good tradeoff between 2D and 3D neuroimaging in terms of scan time and data presentation. These schemes increased the SNR efficiency of currently existing methods and constitute key enablers for the development of SNR efficient MRI.
ContributorsAboussouan, Eric (Author) / Frakes, David (Thesis advisor) / Pipe, James (Thesis advisor) / Debbins, Joseph (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2011
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Description
A specific type of Congenital Heart Defect (CHD) known as Coarctation (narrowing) of the Aorta (CoA) prevails in 10% of all CHD patients resulting in life-threatening conditions. Treatments involve limited medical therapy (i.e PGE1 therapy), but in majority of CoA cases, planned surgical treatments are very common. The surgical approach

A specific type of Congenital Heart Defect (CHD) known as Coarctation (narrowing) of the Aorta (CoA) prevails in 10% of all CHD patients resulting in life-threatening conditions. Treatments involve limited medical therapy (i.e PGE1 therapy), but in majority of CoA cases, planned surgical treatments are very common. The surgical approach is dictated by the severity of the coarctation, by which the method of treatments is divided between minimally invasive and extensive invasive procedures. Modern diagnostic procedures allude to many disadvantages making it difficult for clinical practices to properly deliver an optimal form of care. Computational Fluid Dynamics (CFD) technique addresses these issues by providing new forms of diagnostic measures that is non-invasive, inexpensive, and more accurate compared to other evaluative devices. To explore further using the CFD based alternative diagnostic measure, this project aims to validate CFD techniques through in vitro studies that capture the fluid flow in anatomically accurate aortic structures. These studies combine particle image velocimetry and catheterization experimental techniques in order to provide a significant knowledge towards validation of fluid flow simulations.
ContributorsPathangey, Girish (Co-author) / Matheny, Chris (Co-author) / Frakes, David (Thesis director) / Pophal, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Intracranial aneurysms are blood \u2014filled sacs along the blood vessels in the brain. These aneurysms can be particularly dangerous due to difficulty in detection and potential lifethreatening outcome. When these aneurysms are detected, there are few treatment options to prevent rupture, one of which is endovascular stents. By placing a

Intracranial aneurysms are blood \u2014filled sacs along the blood vessels in the brain. These aneurysms can be particularly dangerous due to difficulty in detection and potential lifethreatening outcome. When these aneurysms are detected, there are few treatment options to prevent rupture, one of which is endovascular stents. By placing a stent across the parent vessel, blood flow can be diverted from the aneurysm. Reduced flow reduces the chance of rupture and promotes clotting within the aneurysm. In this study, hemodynamics in idealized basilar tip aneurysm models were investigated at three flow rates using particle imaging velocimetry (PIV). Two models were created with increasing dome size (4mm vs 6mm), and constant dome-to-neck ratio (3:2) and parent vessel contact angle to represent growing aneurysm. With the pulsatile flow, data is acquired at three separate points in the cardiac cycle. Both of the models were studied untreated, treated with Enterprise stent and treated with Pipeline stent. Enterprise stent was developed mainly for structural support while the Pipeline stent was developed as a flow diverter. Due to target functions of the stents, Enterprise stent is more porous than the Pipeline stent. Hemodynamics were studied using a stereo particle image velocimetry technique. The flow in models was characterized by neck and aneurysmal RMS velocity, neck and aneurysm kinetic energy, cross neck flow. It was found that both of the stents are capable diverting flow. Enterprise reduced aneurysmal RMS velocity in model 1 by 38.7% and in model 2 by 76.2%. Pipeline stent reduced aneurysmal RMS velocity in model 1 by 71.4% and in model 2 by 88.1%. Both reductions are data for 3ml/s at peak systole pulsatile flow. Data shows that the Pipeline stent is better than Enterprise stent at reducing flow to the aneurysm.
ContributorsChung, Hanseung (Author) / Frakes, David (Thesis director) / Caplan, Michael (Committee member) / Babiker, Haithem (Committee member) / Barrett, The Honors College (Contributor) / Economics Program in CLAS (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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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 hemorrhaging (SAH), a possibly fatal condition. One possible treatment involves

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.
ContributorsLindsay, James Bryan (Author) / Frakes, David (Thesis director) / LaBelle, Jeffrey (Committee member) / Nair, Priya (Committee member) / Barrett, The Honors College (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor)
Created2013-05