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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 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.
ContributorsZhang, Wenjie (Author) / Frakes, David (Thesis advisor) / Meldrum, Deirdre (Thesis advisor) / Chao, Shih-hui (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2011
Description
Phase contrast magnetic resonance angiography (PCMRA) is a non-invasive imaging modality that is capable of producing quantitative vascular flow velocity information. The encoding of velocity information can significantly increase the imaging acquisition and reconstruction durations associated with this technique. The purpose of this work is to provide mechanisms for reducing the scan time of a 3D phase contrast exam, so that hemodynamic velocity data may be acquired robustly and with a high sensitivity. The methods developed in this work focus on the reduction of scan duration and reconstruction computation of a neurovascular PCMRA exam. The reductions in scan duration are made through a combination of advances in imaging and velocity encoding methods. The imaging improvements are explored using rapid 3D imaging techniques such as spiral projection imaging (SPI), Fermat looped orthogonally encoded trajectories (FLORET), stack of spirals and stack of cones trajectories. Scan durations are also shortened through the use and development of a novel parallel imaging technique called Pretty Easy Parallel Imaging (PEPI). Improvements in the computational efficiency of PEPI and in general MRI reconstruction are made in the area of sample density estimation and correction of 3D trajectories. A new method of velocity encoding is demonstrated to provide more efficient signal to noise ratio (SNR) gains than current state of the art methods. The proposed velocity encoding achieves improved SNR through the use of high gradient moments and by resolving phase aliasing through the use measurement geometry and non-linear constraints.
ContributorsZwart, Nicholas R (Author) / Frakes, David H (Thesis advisor) / Pipe, James G (Thesis advisor) / Bennett, Kevin M (Committee member) / Debbins, Josef P (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2011
Description
In this thesis I introduce a new direction to computing using nonlinear chaotic dynamics. The main idea is rich dynamics of a chaotic system enables us to (1) build better computers that have a flexible instruction set, and (2) carry out computation that conventional computers are not good at it. Here I start from the theory, explaining how one can build a computing logic block using a chaotic system, and then I introduce a new theoretical analysis for chaos computing. Specifically, I demonstrate how unstable periodic orbits and a model based on them explains and predicts how and how well a chaotic system can do computation. Furthermore, since unstable periodic orbits and their stability measures in terms of eigenvalues are extractable from experimental times series, I develop a time series technique for modeling and predicting chaos computing from a given time series of a chaotic system. After building a theoretical framework for chaos computing I proceed to architecture of these chaos-computing blocks to build a sophisticated computing system out of them. I describe how one can arrange and organize these chaos-based blocks to build a computer. I propose a brand new computer architecture using chaos computing, which shifts the limits of conventional computers by introducing flexible instruction set. Our new chaos based computer has a flexible instruction set, meaning that the user can load its desired instruction set to the computer to reconfigure the computer to be an implementation for the desired instruction set. Apart from direct application of chaos theory in generic computation, the application of chaos theory to speech processing is explained and a novel application for chaos theory in speech coding and synthesizing is introduced. More specifically it is demonstrated how a chaotic system can model the natural turbulent flow of the air in the human speech production system and how chaotic orbits can be used to excite a vocal tract model. Also as another approach to build computing system based on nonlinear system, the idea of Logical Stochastic Resonance is studied and adapted to an autoregulatory gene network in the bacteriophage λ.
ContributorsKia, Behnam (Author) / Ditto, William (Thesis advisor) / Huang, Liang (Committee member) / Lai, Ying-Cheng (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
Description
Sensitivity is a fundamental challenge for in vivo molecular magnetic resonance imaging (MRI). Here, I improve the sensitivity of metal nanoparticle contrast agents by strategically incorporating pure and doped metal oxides in the nanoparticle core, forming a soluble, monodisperse, contrast agent with adjustable T2 or T1 relaxivity (r2 or r1). I first developed a simplified technique to incorporate iron oxides in apoferritin to form "magnetoferritin" for nM-level detection with T2- and T2* weighting. I then explored whether the crystal could be chemically modified to form a particle with high r1. I first adsorbed Mn2+ ions to metal binding sites in the apoferritin pores. The strategic placement of metal ions near sites of water exchange and within the crystal oxide enhance r1, suggesting a mechanism for increasing relaxivity in porous nanoparticle agents. However, the Mn2+ addition was only possible when the particle was simultaneously filled with an iron oxide, resulting in a particle with a high r1 but also a high r2 and making them undetectable with conventional T1-weighting techniques. To solve this problem and decrease the particle r2 for more sensitive detection, I chemically doped the nanoparticles with tungsten to form a disordered W-Fe oxide composite in the apoferritin core. This configuration formed a particle with a r1 of 4,870mM-1s-1 and r2 of 9,076mM-1s-1. These relaxivities allowed the detection of concentrations ranging from 20nM - 400nM in vivo, both passively injected and targeted to the kidney glomerulus. I further developed an MRI acquisition technique to distinguish particles based on r2/r1, and show that three nanoparticles of similar size can be distinguished in vitro and in vivo with MRI. This work forms the basis for a new, highly flexible inorganic approach to design nanoparticle contrast agents for molecular MRI.
ContributorsClavijo Jordan, Maria Veronica (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sherry, A Dean (Committee member) / Wang, Xiao (Committee member) / Yarger, Jeffery (Committee member) / Arizona State University (Publisher)
Created2012
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The object of this study is to charac terize the effect of focused ultrasound stimulation (FUS) on the rat ce rvix which has been observed to speed its ripening during pregnancy. Ce rvical ripening is required for successful fetal delivery. Timed-pregnant Sprague-Dawley rats (n=36) were used. On day 14 of gestation, the FUS system was placed on the body surface of the rat over the cervix and ultrasound energy was applied to cervix for variable times up to 1 hour in the control group, the FUS system was placed on rats but no energy was applied. Daily measurement of cervix light-induced florescence (LIF, photon counts of collagen x-bridge fluorescence) were made on days 16 of gestation and daily until spont-aneous delivery (day22) to estimate changes in cervical ripening. We found that pulses of 680 KHz ultrasound at 25 Hertz, 1 millisecond pulse duration at 1W/cm^2 applied for as little as 30 minutes would immediately afterwards show the cervix to hav e ripened to the degree seen just before delivery on day 22. Delivery times, fetal weights and viability were unaffected in the FUS-treated animals.
ContributorsLuo, Daishen (Author) / Towe, Bruce C (Thesis advisor) / Wang, Xiao (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
Complex dynamical systems consisting interacting dynamical units are ubiquitous in nature and society. Predicting and reconstructing nonlinear dynamics of units and the complex interacting networks among them serves the base for the understanding of a variety of collective dynamical phenomena. I present a general method to address the two outstanding problems as a whole based solely on time-series measurements. The method is implemented by incorporating compressive sensing approach that enables an accurate reconstruction of complex dynamical systems in terms of both nodal equations that determines the self-dynamics of units and detailed coupling patterns among units. The representative advantages of the approach are (i) the sparse data requirement which allows for a successful reconstruction from limited measurements, and (ii) general applicability to identical and nonidentical nodal dynamics, and to networks with arbitrary interacting structure, strength and sizes. Another two challenging problem of significant interest in nonlinear dynamics: (i) predicting catastrophes in nonlinear dynamical systems in advance of their occurrences and (ii) predicting the future state for time-varying nonlinear dynamical systems, can be formulated and solved in the framework of compressive sensing using only limited measurements. Once the network structure can be inferred, the dynamics behavior on them can be investigated, for example optimize information spreading dynamics, suppress cascading dynamics and traffic congestion, enhance synchronization, game dynamics, etc. The results can yield insights to control strategies design in the real-world social and natural systems. Since 2004, there has been a tremendous amount of interest in graphene. The most amazing feature of graphene is that there exists linear energy-momentum relationship when energy is low. The quasi-particles inside the system can be treated as chiral, massless Dirac fermions obeying relativistic quantum mechanics. Therefore, the graphene provides one perfect test bed to investigate relativistic quantum phenomena, such as relativistic quantum chaotic scattering and abnormal electron paths induced by klein tunneling. This phenomenon has profound implications to the development of graphene based devices that require stable electronic properties.
ContributorsYang, Rui (Author) / Lai, Ying-Cheng (Thesis advisor) / Duman, Tolga M. (Committee member) / Akis, Richard (Committee member) / Huang, Liang (Committee member) / Arizona State University (Publisher)
Created2012
Description
What can classical chaos do to quantum systems is a fundamental issue highly relevant to a number of branches in physics. The field of quantum chaos has been active for three decades, where the focus was on non-relativistic quantumsystems described by the Schr¨odinger equation. By developing an efficient method to solve the Dirac equation in the setting where relativistic particles can tunnel between two symmetric cavities through a potential barrier, chaotic cavities are found to suppress the spread in the tunneling rate. Tunneling rate for any given energy assumes a wide range that increases with the energy for integrable classical dynamics. However, for chaotic underlying dynamics, the spread is greatly reduced. A remarkable feature, which is a consequence of Klein tunneling, arise only in relativistc quantum systems that substantial tunneling exists even for particle energy approaching zero. Similar results are found in graphene tunneling devices, implying high relevance of relativistic quantum chaos to the development of such devices. Wave propagation through random media occurs in many physical systems, where interesting phenomena such as branched, fracal-like wave patterns can arise. The generic origin of these wave structures is currently a matter of active debate. It is of fundamental interest to develop a minimal, paradigmaticmodel that can generate robust branched wave structures. In so doing, a general observation in all situations where branched structures emerge is non-Gaussian statistics of wave intensity with an algebraic tail in the probability density function. Thus, a universal algebraic wave-intensity distribution becomes the criterion for the validity of any minimal model of branched wave patterns. Coexistence of competing species in spatially extended ecosystems is key to biodiversity in nature. Understanding the dynamical mechanisms of coexistence is a fundamental problem of continuous interest not only in evolutionary biology but also in nonlinear science. A continuous model is proposed for cyclically competing species and the effect of the interplay between the interaction range and mobility on coexistence is investigated. A transition from coexistence to extinction is uncovered with a non-monotonic behavior in the coexistence probability and switches between spiral and plane-wave patterns arise. Strong mobility can either promote or hamper coexistence, while absent in lattice-based models, can be explained in terms of nonlinear partial differential equations.
ContributorsNi, Xuan (Author) / Lai, Ying-Cheng (Thesis advisor) / Huang, Liang (Committee member) / Yu, Hongbin (Committee member) / Akis, Richard (Committee member) / Arizona State University (Publisher)
Created2012
Description
The goal of the works presented in this volume is to develop a magnetic resonance imaging (MRI) probe for non-invasive detection of extracellular matrix (ECM) underlying fenestrated endothelia. The ECM is the scaffold that supports tissue structure in all organs. In fenestrated structures the such as the kidney glomerulus and the hepatic sinusoid the ECM serves a unique role in blood filtration and is directly exposed to blood plasma. An assessment of the ECM in fenestrated organs such as the kidney and liver reports on the organ's ability to filter blood - a process critical to maintaining homeostasis. Unfortunately, clinical assessment of the ECM in most organs requires biopsy, which is focal and invasive. This work will focus on visualizing the ECM underlying fenestrated endothelia with natural nanoparticles and MRI. The superparamagnetic ferritin protein has been proposed as a useful naturally-derived, MRI-detectable nanoparticle due to its biocompatibility, ease of functionalization, and modifiable metallic core. We will show that cationized ferritin (CF) specifically binds to the anionic proteoglycans of the ECM underlying fenestrated endothelia and that its accumulation is MRI-detectable. We will then demonstrate the use of CF and MRI in identifying and measuring all glomeruli in the kidney. We will also explore the toxicity of intravenously injected CF and consider other avenues for its application, including detection of microstructural changes in the liver due to chronic liver disease. This work will show that CF is useful in detected fenestrated microstructures in small animals and humans alike, indicating that CF may find broad application in detecting and monitoring disease in both preclinical and clinical settings.
ContributorsBeeman, Scott (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram D (Committee member) / Fayad, Zahi A (Committee member) / Pizziconi, Vincent B (Committee member) / Pipe, James G (Committee member) / Arizona State University (Publisher)
Created2012
Description
The aim of this study was to investigate the microstructural sensitivity of the statistical distribution and diffusion kurtosis (DKI) models of non-monoexponential signal attenuation in the brain using diffusion-weighted MRI (DWI). We first developed a simulation of 2-D water diffusion inside simulated tissue consisting of semi-permeable cells and a variable cell size. We simulated a DWI acquisition using a pulsed gradient spin echo (PGSE) pulse sequence, and fitted the models to the simulated DWI signals using b-values up to 2500 s/mm2. For comparison, we calculated the apparent diffusion coefficient (ADC) of the monoexponential model (b-value = 1000 s/mm2). In separate experiments, we varied the cell size (5-10-15 μ), cell volume fraction (0.50-0.65-0.80), and membrane permeability (0.001-0.01-0.1 mm/s) to study how the fitted parameters tracked simulated microstructural changes. The ADC was sensitive to all the simulated microstructural changes except the decrease in membrane permeability. The σstat of the statistical distribution model increased exclusively with a decrease in cell volume fraction. The Kapp of the DKI model increased exclusively with decreased cell size and decreased with increasing membrane permeability. These results suggest that the non-monoexponential models have different, specific microstructural sensitivity, and a combination of the models may give insights into the microstructural underpinning of tissue pathology. Faster PROPELLER DWI acquisitions, such as Turboprop and X-prop, remain subject to phase errors inherent to a gradient echo readout, which ultimately limits the applied turbo factor and thus scan time reductions. This study introduces a new phase correction to Turboprop, called Turboprop+. This technique employs calibration blades, which generate 2-D phase error maps and are rotated in accordance with the data blades, to correct phase errors arising from off-resonance and system imperfections. The results demonstrate that with a small increase in scan time for collecting calibration blades, Turboprop+ had a superior immunity to the off-resonance related artifacts when compared to standard Turboprop and recently proposed X-prop with the high turbo factor (turbo factor = 7). Thus, low specific absorption rate (SAR) and short scan time can be achieved in Turboprop+ using a high turbo factor, while off-resonance related artifacts are minimized.
ContributorsLee, Chu-Yu (Author) / Debbins, Josef P (Thesis advisor) / Bennett, Kevin M (Thesis advisor) / Karam, Lina (Committee member) / Pipe, James G (Committee member) / Arizona State University (Publisher)
Created2012