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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
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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
Description
With the growing popularity of 3d printing in recreational, research, and commercial enterprises new techniques and processes are being developed to improve the quality of parts created. Even so, the anisotropic properties is still a major hindrance of parts manufactured in this method. The goal is to produce parts that

With the growing popularity of 3d printing in recreational, research, and commercial enterprises new techniques and processes are being developed to improve the quality of parts created. Even so, the anisotropic properties is still a major hindrance of parts manufactured in this method. The goal is to produce parts that mimic the strength characteristics of a comparable part of the same design and materials created using injection molding. In achieving this goal the production cost can be reduced by eliminating the initial investment needed for the creation of expensive tooling. This initial investment reduction will allow for a wider variant of products in smaller batch runs to be made available. This thesis implements the use of ultraviolet (UV) illumination for an in-process laser local pre-deposition heating (LLPH). By comparing samples with and without the LLPH process it is determined that applied energy that is absorbed by the polymer is converted to an increase in the interlayer temperature, and resulting in an observed increase in tensile strength over the baseline test samples. The increase in interlayer bonding thus can be considered the dominating factor over polymer degradation.
ContributorsKusel, Scott Daniel (Author) / Hsu, Keng (Thesis advisor) / Sodemann, Angela (Committee member) / Kannan, Arunachala M (Committee member) / Arizona State University (Publisher)
Created2017
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Description
The American Diabetes Association reports that diabetes costs $322 billion annually and affects 29.1 million Americans. The high out-of-pocket cost of managing diabetes can lead to noncompliance causing serious and expensive complications. There is a large market potential for a more cost-effective alternative to the current market standard of screen-printed

The American Diabetes Association reports that diabetes costs $322 billion annually and affects 29.1 million Americans. The high out-of-pocket cost of managing diabetes can lead to noncompliance causing serious and expensive complications. There is a large market potential for a more cost-effective alternative to the current market standard of screen-printed self-monitoring blood glucose (SMBG) strips. Additive manufacturing, specifically 3D printing, is a developing field that is growing in popularity and functionality. 3D printers are now being used in a variety of applications from consumer goods to medical devices. Healthcare delivery will change as the availability of 3D printers expands into patient homes, which will create alternative and more cost-effective methods of monitoring and managing diseases, such as diabetes. 3D printing technology could transform this expensive industry. A 3D printed sensor was designed to have similar dimensions and features to the SMBG strips to comply with current manufacturing standards. To make the sensor electrically active, various conductive filaments were tested and the conductive graphene filament was determined to be the best material for the sensor. Experiments were conducted to determine the optimal print settings for printing this filament onto a mylar substrate, the industry standard. The reagents used include a mixture of a ferricyanide redox mediator and flavin adenine dinucleotide dependent glucose dehydrogenase. With these materials, each sensor only costs $0.40 to print and use. Before testing the 3D printed sensor, a suitable design, voltage range, and redox probe concentration were determined. Experiments demonstrated that this novel 3D printed sensor can accurately correlate current output to glucose concentration. It was verified that the sensor can accurately detect glucose levels from 25 mg/dL to 400 mg/dL, with an R2 correlation value as high as 0.97, which was critical as it covered hypoglycemic to hyperglycemic levels. This demonstrated that a 3D-printed sensor was created that had characteristics that are suitable for clinical use. This will allow diabetics to print their own test strips at home at a much lower cost compared to SMBG strips, which will reduce noncompliance due to the high cost of testing. In the future, this technology could be applied to additional biomarkers to measure and monitor other diseases.
ContributorsAdams, Anngela (Author) / LaBelle, Jeffrey (Thesis advisor) / Pizziconi, Vincent (Committee member) / Abbas, James (Committee member) / Arizona State University (Publisher)
Created2017
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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
Description
Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) has enabled the determination of damage-free protein structures at ambient temperatures and of reaction intermediate species with time resolution on the order of hundreds of femtoseconds. However, currently available XFEL facility X-ray pulse structures waste the majority of continuously injected

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) has enabled the determination of damage-free protein structures at ambient temperatures and of reaction intermediate species with time resolution on the order of hundreds of femtoseconds. However, currently available XFEL facility X-ray pulse structures waste the majority of continuously injected crystal sample, requiring a large quantity (up to grams) of crystal sample to solve a protein structure. Furthermore, mix-and-inject serial crystallography (MISC) at XFEL facilities requires fast mixing for short (millisecond) reaction time points (𝑡"), and current sample delivery methods have complex fabrication and assembly requirements.

To reduce sample consumption during SFX, a 3D printed T-junction for generating segmented aqueous-in-oil droplets was developed. The device surface properties were characterized both with and without a surface coating for improved droplet generation stability. Additionally, the droplet generation frequency was characterized. The 3D printed device interfaced with gas dynamic virtual nozzles (GDVNs) at the Linac Coherent Light Source (LCLS), and a relationship between the aqueous phase volume and the resulting crystal hit rate was developed. Furthermore, at the European XFEL (EuXFEL) a similar quantity and quality of diffraction data was collected for segmented sample delivery using ~60% less sample volume than continuous injection, and a structure of 3-deoxy-D-manno- octulosonate 8-phosphate synthase (KDO8PS) delivered by segmented injection was solved that revealed new structural details to a resolution of 2.8 Ă….

For MISC, a 3D printed hydrodynamic focusing mixer for fast mixing by diffusion was developed to automate device fabrication and simplify device assembly. The mixer was characterized with numerical models and fluorescence microscopy. A variety of devices were developed to reach reaction intermediate time points, 𝑡", on the order of 100 – 103 ms. These devices include 3D printed mixers coupled to glass or 3D printed GDVNs and two designs of mixers with GDVNs integrated into the one device. A 3D printed mixer coupled to a glass GDVN was utilized at LCLS to study the oxidation of cytochrome c oxidase (CcO), and a structure of the CcO Pr intermediate was determined at 𝑡" = 8 s.
ContributorsEchelmeier, Austin (Author) / Ros, Alexandra (Thesis advisor) / Levitus, Marcia (Committee member) / Weierstall, Uwe (Committee member) / Arizona State University (Publisher)
Created2019