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

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

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to support future improvements in scan time and resolution. SNR efficiency is improved by sampling data for a larger proportion of

Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to support future improvements in scan time and resolution. SNR efficiency is improved by sampling data for a larger proportion of total imaging time. This is challenging as these acquisitions are typically subject to artifacts such as blurring and distortions. The current work proposes a set of tools to help with the creation of different types of SNR efficient scans. An SNR efficient pulse sequence providing diffusion imaging data with full brain coverage and minimal distortion is first introduced. The proposed method acquires single-shot, low resolution image slabs which are then combined to reconstruct the full volume. An iterative deblurring algorithm allowing the lengthening of spiral SPoiled GRadient echo (SPGR) acquisition windows in the presence of rapidly varying off-resonance fields is then presented. Finally, an efficient and practical way of collecting 3D reformatted data is proposed. This method constitutes a good tradeoff between 2D and 3D neuroimaging in terms of scan time and data presentation. These schemes increased the SNR efficiency of currently existing methods and constitute key enablers for the development of SNR efficient MRI.
ContributorsAboussouan, Eric (Author) / Frakes, David (Thesis advisor) / Pipe, James (Thesis advisor) / Debbins, Joseph (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Image segmentation is of great importance and value in many applications. In computer vision, image segmentation is the tool and process of locating objects and boundaries within images. The segmentation result may provide more meaningful image data. Generally, there are two fundamental image segmentation algorithms: discontinuity and similarity. The idea

Image segmentation is of great importance and value in many applications. In computer vision, image segmentation is the tool and process of locating objects and boundaries within images. The segmentation result may provide more meaningful image data. Generally, there are two fundamental image segmentation algorithms: discontinuity and similarity. The idea behind discontinuity is locating the abrupt changes in intensity of images, as are often seen in edges or boundaries. Similarity subdivides an image into regions that fit the pre-defined criteria. The algorithm utilized in this thesis is the second category.

This study addresses the problem of particle image segmentation by measuring the similarity between a sampled region and an adjacent region, based on Bhattacharyya distance and an image feature extraction technique that uses distribution of local binary patterns and pattern contrasts. A boundary smoothing process is developed to improve the accuracy of the segmentation. The novel particle image segmentation algorithm is tested using four different cases of particle image velocimetry (PIV) images. The obtained experimental results of segmentations provide partitioning of the objects within 10 percent error rate. Ground-truth segmentation data, which are manually segmented image from each case, are used to calculate the error rate of the segmentations.
ContributorsHan, Dongmin (Author) / Frakes, David (Thesis advisor) / Adrian, Ronald (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2015
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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