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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

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
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Description
Computed tomography (CT) is one of the essential imaging modalities for medical diagnosis. Since its introduction in 1972, CT technology has been improved dramatically, especially in terms of its acquisition speed. However, the main principle of CT which consists in acquiring only density information has not changed at all

Computed tomography (CT) is one of the essential imaging modalities for medical diagnosis. Since its introduction in 1972, CT technology has been improved dramatically, especially in terms of its acquisition speed. However, the main principle of CT which consists in acquiring only density information has not changed at all until recently. Different materials may have the same CT number, which may lead to uncertainty or misdiagnosis. Dual-energy CT (DECT) was reintroduced recently to solve this problem by using the additional spectral information of X-ray attenuation and aims for accurate density measurement and material differentiation. However, the spectral information lies in the difference between two low and high energy images or measurements, so that it is difficult to acquire the accurate spectral information due to amplification of high pixel noise in the resulting difference image. In this work, a new model and an image enhancement technique for DECT are proposed, based on the fact that the attenuation of a high density material decreases more rapidly as X-ray energy increases. This fact has been previously ignored in most of DECT image enhancement techniques. The proposed technique consists of offset correction, spectral error correction, and adaptive noise suppression. It reduced noise, improved contrast effectively and showed better material differentiation in real patient images as well as phantom studies.
ContributorsPark, Kyung Kook (Author) / Metin, Akay (Thesis advisor) / Pavlicek, William (Committee member) / Akay, Yasemin (Committee member) / Towe, Bruce (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2011
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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

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
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Description
Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of gri

Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of grip and load force rates during the period between initial contact with the object and object lift. However, this has not been validated in tasks that do not constrain digit placement. The purposes of this thesis were (1) to validate the hypothesis that force rate profiles are indicative of the control strategy used for object manipulation and (2) to test this hypothesis by comparing manipulation tasks performed with and without digit placement constraints. The first objective comprised two studies. In the first study an additional light or heavy mass was added to the base of the object. In the second study a mass was added, altering the object's center of mass (CM) location. In each experiment digit force rates were calculated between the times of initial digit contact and object lift. Digit force rates were fit to a Gaussian bell curve and the goodness of fit was compared across predictable and unpredictable mass and CM conditions. For both experiments, a predictable object mass and CM elicited bell shaped force rate profiles, indicative of feedforward control. For the second objective, a comparison of performance between subjects who performed the grasp task with either constrained or unconstrained digit contact locations was conducted. When digit location was unconstrained and CM was predictable, force rates were well fit to a bell shaped curve. However, the goodness of fit of the force rate profiles to the bell shaped curve was weaker for the constrained than the unconstrained digit placement condition. These findings seem to indicate that brain can generate an appropriate feedforward control strategy even when digit placement is unconstrained and an infinite combination of digit placement and force solutions exists to lift the object successfully. Future work is needed that investigates the role digit positioning and tactile feedback has on anticipatory control of object manipulation.
ContributorsCooperhouse, Michael A (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2011
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Description
A noninvasive optical method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm that is a peak absorbance of hemoglobin. As the glucose concentration in the blood decreases, its

A noninvasive optical method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm that is a peak absorbance of hemoglobin. As the glucose concentration in the blood decreases, its osmolarity also decreases and the RBCs swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds. The changes in size of the RBC cells in response to glucose concentration changes were confirmed using a cell counter and also visually under microscope. This method does not allow measuring the glucose concentration with an absolute concentration calibration. It is directed towards development of a device to monitor the changes in glucose concentration as an aid to diabetic management. This method might be improvised for precision and resolution and be developed as a ring or an earring that patients can wear.
ContributorsRajan, Shiny Amala Priya (Author) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Image resolution limits the extent to which zooming enhances clarity, restricts the size digital photographs can be printed at, and, in the context of medical images, can prevent a diagnosis. Interpolation is the supplementing of known data with estimated values based on a function or model involving some or all

Image resolution limits the extent to which zooming enhances clarity, restricts the size digital photographs can be printed at, and, in the context of medical images, can prevent a diagnosis. Interpolation is the supplementing of known data with estimated values based on a function or model involving some or all of the known samples. The selection of the contributing data points and the specifics of how they are used to define the interpolated values influences how effectively the interpolation algorithm is able to estimate the underlying, continuous signal. The main contributions of this dissertation are three fold: 1) Reframing edge-directed interpolation of a single image as an intensity-based registration problem. 2) Providing an analytical framework for intensity-based registration using control grid constraints. 3) Quantitative assessment of the new, single-image enlargement algorithm based on analytical intensity-based registration. In addition to single image resizing, the new methods and analytical approaches were extended to address a wide range of applications including volumetric (multi-slice) image interpolation, video deinterlacing, motion detection, and atmospheric distortion correction. Overall, the new approaches generate results that more accurately reflect the underlying signals than less computationally demanding approaches and with lower processing requirements and fewer restrictions than methods with comparable accuracy.
ContributorsZwart, Christine M. (Author) / Frakes, David H (Thesis advisor) / Karam, Lina (Committee member) / Kodibagkar, Vikram (Committee member) / Spanias, Andreas (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2013
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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
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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).

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
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Description
Millions of Americans live with motor impairments resulting from a stroke and the best way to administer rehabilitative therapy to achieve recovery is not well understood. Adaptive mixed reality rehabilitation (AMRR) is a novel integration of motion capture technology and high-level media computing that provides precise kinematic measurements and engaging

Millions of Americans live with motor impairments resulting from a stroke and the best way to administer rehabilitative therapy to achieve recovery is not well understood. Adaptive mixed reality rehabilitation (AMRR) is a novel integration of motion capture technology and high-level media computing that provides precise kinematic measurements and engaging multimodal feedback for self-assessment during a therapeutic task. The AMRR system was evaluated in a small (N=3) cohort of stroke survivors to determine best practices for administering adaptive, media-based therapy. A proof of concept study followed, examining changes in clinical scale and kinematic performances among a group of stroke survivors who received either a month of AMRR therapy (N = 11) or matched dosing of traditional repetitive task therapy (N = 10). Both groups demonstrated statistically significant improvements in Wolf Motor Function Test and upper-extremity Fugl-Meyer Assessment scores, indicating increased function after the therapy. However, only participants who received AMRR therapy showed a consistent improvement in their kinematic measurements, including those measured in the trained reaching task (reaching to grasp a cone) and in an untrained reaching task (reaching to push a lighted button). These results suggest that that the AMRR system can be used as a therapy tool to enhance both functionality and reaching kinematics that quantify movement quality. Additionally, the AMRR concepts are currently being transitioned to a home-based training application. An inexpensive, easy-to-use, toolkit of tangible objects has been developed to sense, assess and provide feedback on hand function during different functional activities. These objects have been shown to accurately and consistently track hand function in people with unimpaired movements and will be tested with stroke survivors in the future.
ContributorsDuff, Margaret Rose (Author) / Rikakis, Thanassis (Thesis advisor) / He, Jiping (Thesis advisor) / Herman, Richard (Committee member) / Kleim, Jeffrey (Committee member) / Santos, Veronica (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions

Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013