Matching Items (15)
Filtering by

Clear all filters

150080-Thumbnail Image.png
Description
Treatment of cerebral aneurysms using non-invasive methods has existed for decades. Since the advent of modern endovascular techniques, advancements to embolic materials have largely focused on improving platinum coil technology. However, the recent development of Onyx®, a liquid-delivery precipitating polymer system, has opened the door for a new class of

Treatment of cerebral aneurysms using non-invasive methods has existed for decades. Since the advent of modern endovascular techniques, advancements to embolic materials have largely focused on improving platinum coil technology. However, the recent development of Onyx®, a liquid-delivery precipitating polymer system, has opened the door for a new class of embolic materials--liquid-fill systems. These liquid-fill materials have the potential to provide better treatment outcomes than platinum coils. Initial clinical use of Onyx has proven promising, but not without substantial drawbacks, such as co-delivery of angiotoxic compounds and an extremely technical delivery procedure. This work focuses on formulation, characterization and testing of a novel liquid-to-solid gelling polymer system, based on poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT). The PPODA-QT system bypasses difficulties associated with Onyx embolization, yet still maintains non-invasive liquid delivery--exhibiting the properties of an ideal embolic material for cerebral aneurysm embolization. To allow for material visibility during clinical delivery, an embolic material must be radio-opaque. The PPODA-QT system was formulated with commercially available contrast agents and the gelling kinetics were studied, as a complete understanding of the gelling process is vital for clinical use. These PPODA-QT formulations underwent in vitro characterization of material properties including cytotoxicity, swelling, and degradation behaviors. Formulation and characterization tests led to an optimized PPODA-QT formulation that was used in subsequent in vivo testing. PPODA-QT formulated with the liquid contrast agent ConrayTM was used in the first in vivo studies. These studies employed a swine aneurysm model to assess initial biocompatibility and test different delivery strategies of PPODA-QT. Results showed good biocompatibility and a suitable delivery strategy, providing justification for further in vivo testing. PPODA-QT was then used in a small scale pilot study to gauge long-term effectiveness of the material in a clinically-relevant aneurysm model. Results from the pilot study showed that PPODA-QT has the capability to provide successful, long-term treatment of model aneurysms as well as facilitate aneurysm healing.
ContributorsRiley, Celeste (Author) / Vernon, Brent L (Thesis advisor) / Preul, Mark C (Committee member) / Frakes, David (Committee member) / Pauken, Christine (Committee member) / Massia, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
151857-Thumbnail Image.png
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
152201-Thumbnail Image.png
Description
Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After

Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques.
ContributorsBoltz, Thomas (Author) / Frakes, David (Thesis advisor) / Towe, Bruce (Committee member) / Kodibagkar, Vikram (Committee member) / Pavlicek, William (Committee member) / Bouman, Charles (Committee member) / Arizona State University (Publisher)
Created2013
151306-Thumbnail Image.png
Description
Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of

Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of microscale sensors that are used for sensing applications, ranging from whole-body monitoring down to molecular sensing. Unfortunately, sensors are often developed without regard to how they will be integrated into biological systems. The complexities of integration are underappreciated. Integration involves more than simply making electrical connections. Interfacing microscale sensors with biological environments requires numerous considerations with respect to the creation of compatible packaging, the management of biological reagents, and the act of combining technologies with different dimensions and material properties. Recent advances in microfluidics, especially the proliferation of soft lithography manufacturing methods, have established the groundwork for creating systems that may solve many of the problems inherent to sensor-fluidic interaction. The adaptation of microelectronics manufacturing methods, such as Complementary Metal-Oxide-Semiconductor (CMOS) and Microelectromechanical Systems (MEMS) processes, allows the creation of a complete biological sensing system with integrated sensors and readout circuits. Combining these technologies is an obstacle to forming complete sensor systems. This dissertation presents new approaches for the design, fabrication, and integration of microscale sensors and microelectronics with microfluidics. The work addresses specific challenges, such as combining commercial manufacturing processes into biological systems and developing microscale sensors in these processes. This work is exemplified through a feedback-controlled microfluidic pH system to demonstrate the integration capabilities of microscale sensors for autonomous microenvironment control.
ContributorsWelch, David (Author) / Blain Christen, Jennifer (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Frakes, David (Committee member) / LaBelle, Jeffrey (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2012
150720-Thumbnail Image.png
Description
Current treatment methods for cerebral aneurysms are providing life-saving measures for patients suffering from these blood vessel wall protrusions; however, the drawbacks present unfortunate circumstances in the invasive procedure or with efficient occlusion of the aneurysms. With the advancement of medical devices, liquid-to-solid gelling materials that could be delivered endovascularly

Current treatment methods for cerebral aneurysms are providing life-saving measures for patients suffering from these blood vessel wall protrusions; however, the drawbacks present unfortunate circumstances in the invasive procedure or with efficient occlusion of the aneurysms. With the advancement of medical devices, liquid-to-solid gelling materials that could be delivered endovascularly have gained interest. The development of these systems stems from the need to circumvent surgical methods and the requirement for improved occlusion of aneurysms to prevent recanalization and potential complications. The work presented herein reports on a liquid-to-solid gelling material, which undergoes gelation via dual mechanisms. Using a temperature-responsive polymer, poly(N-isopropylacrylamide) (poly(NIPAAm), the gelling system can transition from a solution at low temperatures to a gel at body temperature (physical gelation). Additionally, by conjugating reactive functional groups onto the polymers, covalent cross-links can be formed via chemical reaction between the two moieties (chemical gelation). The advantage of this gelling system comprises of its water-based properties as well as the ability of the physical and chemical gelation to occur within physiological conditions. By developing the polymer gelling system in a ground-up approach via synthesis, its added benefit is the capability of modifying the properties of the system as needed for particular applications, in this case for embolization of cerebral aneurysms. The studies provided in this doctoral work highlight the synthesis, characterization and testing of these polymer gelling systems for occlusion of aneurysms. Conducted experiments include thermal, mechanical, structural and chemical characterization, as well as analysis of swelling, degradation, kinetics, cytotoxicity, in vitro glass models and in vivo swine study. Data on thermoresponsive poly(NIPAAm) indicated that the phase transition it undertakes comes as a result of the polymer chains associating as temperature is increased. Poly(NIPAAm) was functionalized with thiols and vinyls to provide for added chemical cross-linking. By combining both modes of gelation, physical and chemical, a gel with reduced creep flow and increased strength was developed. Being waterborne, the gels demonstrated excellent biocompatibility and were easily delivered via catheters and injected within aneurysms, without undergoing degradation. The dual gelling polymer systems demonstrated potential in use as embolic agents for cerebral aneurysm embolization.
ContributorsBearat, Hanin H (Author) / Vernon, Brent L (Thesis advisor) / Frakes, David (Committee member) / Massia, Stephen (Committee member) / Pauken, Christine (Committee member) / Preul, Mark (Committee member) / Solis, Francisco (Committee member) / Arizona State University (Publisher)
Created2012
154254-Thumbnail Image.png
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 pathologies and for planning their surgical repair. In vitro experiments

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.
ContributorsChaudhury, Rafeed Ahmed (Author) / Frakes, David (Thesis advisor) / Adrian, Ronald J (Thesis advisor) / Vernon, Brent (Committee member) / Pizziconi, Vincent (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2015
154534-Thumbnail Image.png
Description
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 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.
ContributorsNair, Priya (Author) / Frakes, David (Thesis advisor) / Vernon, Brent (Committee member) / Chong, Brian (Committee member) / Pizziconi, Vincent (Committee member) / Adrian, Ronald (Committee member) / Arizona State University (Publisher)
Created2016
154928-Thumbnail Image.png
Description
Magnetic resonance spectroscopic imaging (MRSI) is a valuable technique for assessing the in vivo spatial profiles of metabolites like N-acetylaspartate (NAA), creatine, choline, and lactate. Changes in metabolite concentrations can help identify tissue heterogeneity, providing prognostic and diagnostic information to the clinician. The increased uptake of glucose by solid tumors

Magnetic resonance spectroscopic imaging (MRSI) is a valuable technique for assessing the in vivo spatial profiles of metabolites like N-acetylaspartate (NAA), creatine, choline, and lactate. Changes in metabolite concentrations can help identify tissue heterogeneity, providing prognostic and diagnostic information to the clinician. The increased uptake of glucose by solid tumors as compared to normal tissues and its conversion to lactate can be exploited for tumor diagnostics, anti-cancer therapy, and in the detection of metastasis. Lactate levels in cancer cells are suggestive of altered metabolism, tumor recurrence, and poor outcome. A dedicated technique like MRSI could contribute to an improved assessment of metabolic abnormalities in the clinical setting, and introduce the possibility of employing non-invasive lactate imaging as a powerful prognostic marker.

However, the long acquisition time in MRSI is a deterrent to its inclusion in clinical protocols due to associated costs, patient discomfort (especially in pediatric patients under anesthesia), and higher susceptibility to motion artifacts. Acceleration strategies like compressed sensing (CS) permit faithful reconstructions even when the k-space is undersampled well below the Nyquist limit. CS is apt for MRSI as spectroscopic data are inherently sparse in multiple dimensions of space and frequency in an appropriate transform domain, for e.g. the wavelet domain. The objective of this research was three-fold: firstly on the preclinical front, to prospectively speed-up spectrally-edited MRSI using CS for rapid mapping of lactate and capture associated changes in response to therapy. Secondly, to retrospectively evaluate CS-MRSI in pediatric patients scanned for various brain-related concerns. Thirdly, to implement prospective CS-MRSI acquisitions on a clinical magnetic resonance imaging (MRI) scanner for fast spectroscopic imaging studies. Both phantom and in vivo results demonstrated a reduction in the scan time by up to 80%, with the accelerated CS-MRSI reconstructions maintaining high spectral fidelity and statistically insignificant errors as compared to the fully sampled reference dataset. Optimization of CS parameters involved identifying an optimal sampling mask for CS-MRSI at each acceleration factor. It is envisioned that time-efficient MRSI realized with optimized CS acceleration would facilitate the clinical acceptance of routine MRSI exams for a quantitative mapping of important biomarkers.
ContributorsVidya Shankar, Rohini (Author) / Kodibagkar, Vikram D (Thesis advisor) / Pipe, James (Committee member) / Chang, John (Committee member) / Sadleir, Rosalind (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2016
153276-Thumbnail Image.png
Description
Cigarette smoking remains a major global public health issue. This is partially due to the chronic and relapsing nature of tobacco use, which contributes to the approximately 90% quit attempt failure rate. The recent rise in mobile technologies has led to an increased ability to frequently measure smoking behaviors and

Cigarette smoking remains a major global public health issue. This is partially due to the chronic and relapsing nature of tobacco use, which contributes to the approximately 90% quit attempt failure rate. The recent rise in mobile technologies has led to an increased ability to frequently measure smoking behaviors and related constructs over time, i.e., obtain intensive longitudinal data (ILD). Dynamical systems modeling and system identification methods from engineering offer a means to leverage ILD in order to better model dynamic smoking behaviors. In this dissertation, two sets of dynamical systems models are estimated using ILD from a smoking cessation clinical trial: one set describes cessation as a craving-mediated process; a second set was reverse-engineered and describes a psychological self-regulation process in which smoking activity regulates craving levels. The estimated expressions suggest that self-regulation more accurately describes cessation behavior change, and that the psychological self-regulator resembles a proportional-with-filter controller. In contrast to current clinical practice, adaptive smoking cessation interventions seek to personalize cessation treatment over time. An intervention of this nature generally reflects a control system with feedback and feedforward components, suggesting its design could benefit from a control systems engineering perspective. An adaptive intervention is designed in this dissertation in the form of a Hybrid Model Predictive Control (HMPC) decision algorithm. This algorithm assigns counseling, bupropion, and nicotine lozenges each day to promote tracking of target smoking and craving levels. Demonstrated through a diverse series of simulations, this HMPC-based intervention can aid a successful cessation attempt. Objective function weights and three-degree-of-freedom tuning parameters can be sensibly selected to achieve intervention performance goals despite strict clinical and operational constraints. Such tuning largely affects the rate at which peak bupropion and lozenge dosages are assigned; total post-quit smoking levels, craving offset, and other performance metrics are consequently affected. Overall, the interconnected nature of the smoking and craving controlled variables facilitate the controller's robust decision-making capabilities, even despite the presence of noise or plant-model mismatch. Altogether, this dissertation lays the conceptual and computational groundwork for future efforts to utilize engineering concepts to further study smoking behaviors and to optimize smoking cessation interventions.
ContributorsTimms, Kevin Patrick (Author) / Rivera, Daniel E (Thesis advisor) / Frakes, David (Committee member) / Nielsen, David R (Committee member) / Arizona State University (Publisher)
Created2014
153581-Thumbnail Image.png
Description
The advent of medical imaging has enabled significant advances in pre-procedural planning, allowing cardiovascular anatomy to be visualized noninvasively before a procedure. However, absolute scale and tactile information are not conveyed in traditional pre-procedural planning based on images alone. This information deficit fails to completely prepare clinicians for complex heart

The advent of medical imaging has enabled significant advances in pre-procedural planning, allowing cardiovascular anatomy to be visualized noninvasively before a procedure. However, absolute scale and tactile information are not conveyed in traditional pre-procedural planning based on images alone. This information deficit fails to completely prepare clinicians for complex heart repair, where surgeons must consider the varied presentations of cardiac morphology and malformations. Three-dimensional (3D) visualization and 3D printing provide a mechanism to construct patient-specific, scale models of cardiovascular anatomy that surgeons and interventionalists can examine prior to a procedure. In addition, the same patient-specific models provide a valuable resource for educating future medical professionals. Instead of looking at idealized images on a computer screen or pages from medical textbooks, medical students can review a life-like model of patient anatomy.



In cases where surgical repair is insufficient to return the heart to normal function, a patient may proceed to advanced heart failure, and a heart transplant may be required. Unfortunately, a finite number of available donor hearts are available. A mechanical circulatory support (MCS) device can be used to bridge the time between heart failure and reception of a donor heart. These MCS devices are typically constructed for the adult population. Accordingly, the size associated to the device is a limiting factor for small adults or pediatric patients who often have smaller thoracic measurements. While current eligibility criteria are based on correlative measurements, the aforementioned 3D visualization capabilities can be leveraged to accomplish patient-specific fit analysis.

The main objectives of the work presented in this dissertation were 1) to develop and evaluate an optimized process for 3D printing cardiovascular anatomy for surgical planning and medical education and 2) to develop and evaluate computational tools to assess MCS device fit in specific patients. The evaluations for objectives 1 and 2 were completed with a collection of qualitative and quantitative validations. These validations include case studies to illustrate meaningful, qualitative results as well as quantitative results from surgical outcomes. The latter results present the first quantitative supporting evidence, beyond anecdotal case studies, regarding the efficacy of 3D printing for pre-procedural planning; this data is suitable as pilot data for clinical trials. The products of this work were used to plan 200 cardiovascular procedures (including 79 cardiothoracic surgeries at Phoenix Children's Hospital), via 3D printed heart models and assess MCS device fit in 29 patients across 6 countries.
ContributorsRyan, Justin Robert (Author) / Frakes, David (Thesis advisor) / Collins, Daniel (Committee member) / LaBelle, Jeffrey (Committee member) / Pizziconi, Vincent (Committee member) / Pophal, Stephen (Committee member) / Arizona State University (Publisher)
Created2015