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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
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
Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge

Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge in both of the aforementioned applications is the efficient delivery of siRNA molecules, plasmids or transcription factors to primary cells such as neurons. A majority of the current non-viral techniques, including chemical transfection, bulk electroporation and sonoporation fail to deliver with adequate efficiencies and the required spatial and temporal control. In this study, a novel optically transparent biochip is presented that can (a) transfect populations of primary and secondary cells in 2D culture (b) readily scale to realize high-throughput transfections using microscale electroporation and (c) transfect targeted cells in culture with spatial and temporal control. In this study, delivery of genetic payloads of different sizes and molecular characteristics, such as GFP plasmids and siRNA molecules, to precisely targeted locations in primary hippocampal and HeLa cell cultures is demonstrated. In addition to spatio-temporally controlled transfection, the biochip also allowed simultaneous assessment of a) electrical activity of neurons, b) specific proteins using fluorescent immunohistochemistry, and c) sub-cellular structures. Functional silencing of GAPDH in HeLa cells using siRNA demonstrated a 52% reduction in the GAPDH levels. In situ assessment of actin filaments post electroporation indicated a sustained disruption in actin filaments in electroporated cells for up to two hours. Assessment of neural spike activity pre- and post-electroporation indicated a varying response to electroporation. The microarray based nature of the biochip enables multiple independent experiments on the same culture, thereby decreasing culture-to-culture variability, increasing experimental throughput and allowing cell-cell interaction studies. Further development of this technology will provide a cost-effective platform for performing high-throughput genetic screens.
ContributorsPatel, Chetan (Author) / Muthuswamy, Jitendran (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Jain, Tilak (Committee member) / Caplan, Michael (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The use of electromyography (EMG) signals to characterize muscle fatigue has been widely accepted. Initial work on characterizing muscle fatigue during isometric contractions demonstrated that its frequency decreases while its amplitude increases with the onset of fatigue. More recent work concentrated on developing techniques to characterize dynamic contractions for use

The use of electromyography (EMG) signals to characterize muscle fatigue has been widely accepted. Initial work on characterizing muscle fatigue during isometric contractions demonstrated that its frequency decreases while its amplitude increases with the onset of fatigue. More recent work concentrated on developing techniques to characterize dynamic contractions for use in clinical and training applications. Studies demonstrated that as fatigue progresses, the EMG signal undergoes a shift in frequency, and different physiological mechanisms on the possible cause of the shift were considered. Time-frequency processing, using the Wigner distribution or spectrogram, is one of the techniques used to estimate the instantaneous mean frequency and instantaneous median frequency of the EMG signal using a variety of techniques. However, these time-frequency methods suffer either from cross-term interference when processing signals with multiple components or time-frequency resolution due to the use of windowing. This study proposes the use of the matching pursuit decomposition (MPD) with a Gaussian dictionary to process EMG signals produced during both isometric and dynamic contractions. In particular, the MPD obtains unique time-frequency features that represent the EMG signal time-frequency dependence without suffering from cross-terms or loss in time-frequency resolution. As the MPD does not depend on an analysis window like the spectrogram, it is more robust in applying the timefrequency features to identify the spectral time-variation of the EGM signal.
ContributorsAustin, Hiroko (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Kovvali, Narayan (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Statistical process control (SPC) and predictive analytics have been used in industrial manufacturing and design, but up until now have not been applied to threshold data of vital sign monitoring in remote care settings. In this study of 20 elders with COPD and/or CHF, extended months of peak flow monitoring

Statistical process control (SPC) and predictive analytics have been used in industrial manufacturing and design, but up until now have not been applied to threshold data of vital sign monitoring in remote care settings. In this study of 20 elders with COPD and/or CHF, extended months of peak flow monitoring (FEV1) using telemedicine are examined to determine when an earlier or later clinical intervention may have been advised. This study demonstrated that SPC may bring less than a 2.0% increase in clinician workload while providing more robust statistically-derived thresholds than clinician-derived thresholds. Using a random K-fold model, FEV1 output was predictably validated to .80 Generalized R-square, demonstrating the adequate learning of a threshold classifier. Disease severity also impacted the model. Forecasting future FEV1 data points is possible with a complex ARIMA (45, 0, 49), but variation and sources of error require tight control. Validation was above average and encouraging for clinician acceptance. These statistical algorithms provide for the patient's own data to drive reduction in variability and, potentially increase clinician efficiency, improve patient outcome, and cost burden to the health care ecosystem.
ContributorsFralick, Celeste (Author) / Muthuswamy, Jitendran (Thesis advisor) / O'Shea, Terrance (Thesis advisor) / LaBelle, Jeffrey (Committee member) / Pizziconi, Vincent (Committee member) / Shea, Kimberly (Committee member) / Arizona State University (Publisher)
Created2013
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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
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Description
Electrical neural activity detection and tracking have many applications in medical research and brain computer interface technologies. In this thesis, we focus on the development of advanced signal processing algorithms to track neural activity and on the mapping of these algorithms onto hardware to enable real-time tracking. At the heart

Electrical neural activity detection and tracking have many applications in medical research and brain computer interface technologies. In this thesis, we focus on the development of advanced signal processing algorithms to track neural activity and on the mapping of these algorithms onto hardware to enable real-time tracking. At the heart of these algorithms is particle filtering (PF), a sequential Monte Carlo technique used to estimate the unknown parameters of dynamic systems. First, we analyze the bottlenecks in existing PF algorithms, and we propose a new parallel PF (PPF) algorithm based on the independent Metropolis-Hastings (IMH) algorithm. We show that the proposed PPF-IMH algorithm improves the root mean-squared error (RMSE) estimation performance, and we demonstrate that a parallel implementation of the algorithm results in significant reduction in inter-processor communication. We apply our implementation on a Xilinx Virtex-5 field programmable gate array (FPGA) platform to demonstrate that, for a one-dimensional problem, the PPF-IMH architecture with four processing elements and 1,000 particles can process input samples at 170 kHz by using less than 5% FPGA resources. We also apply the proposed PPF-IMH to waveform-agile sensing to achieve real-time tracking of dynamic targets with high RMSE tracking performance. We next integrate the PPF-IMH algorithm to track the dynamic parameters in neural sensing when the number of neural dipole sources is known. We analyze the computational complexity of a PF based method and propose the use of multiple particle filtering (MPF) to reduce the complexity. We demonstrate the improved performance of MPF using numerical simulations with both synthetic and real data. We also propose an FPGA implementation of the MPF algorithm and show that the implementation supports real-time tracking. For the more realistic scenario of automatically estimating an unknown number of time-varying neural dipole sources, we propose a new approach based on the probability hypothesis density filtering (PHDF) algorithm. The PHDF is implemented using particle filtering (PF-PHDF), and it is applied in a closed-loop to first estimate the number of dipole sources and then their corresponding amplitude, location and orientation parameters. We demonstrate the improved tracking performance of the proposed PF-PHDF algorithm and map it onto a Xilinx Virtex-5 FPGA platform to show its real-time implementation potential. Finally, we propose the use of sensor scheduling and compressive sensing techniques to reduce the number of active sensors, and thus overall power consumption, of electroencephalography (EEG) systems. We propose an efficient sensor scheduling algorithm which adaptively configures EEG sensors at each measurement time interval to reduce the number of sensors needed for accurate tracking. We combine the sensor scheduling method with PF-PHDF and implement the system on an FPGA platform to achieve real-time tracking. We also investigate the sparsity of EEG signals and integrate compressive sensing with PF to estimate neural activity. Simulation results show that both sensor scheduling and compressive sensing based methods achieve comparable tracking performance with significantly reduced number of sensors.
ContributorsMiao, Lifeng (Author) / Chakrabarti, Chaitali (Thesis advisor) / Papandreou-Suppappola, Antonia (Thesis advisor) / Zhang, Junshan (Committee member) / Bliss, Daniel (Committee member) / Kovvali, Narayan (Committee member) / Arizona State University (Publisher)
Created2013
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Description
A cerebral aneurysm is a bulging of a blood vessel in the brain. Aneurysmal rupture affects 25,000 people each year and is associated with a 45% mortality rate. Therefore, it is critically important to treat cerebral aneurysms effectively before they rupture. Endovascular coiling is the most effective treatment for cerebral

A cerebral aneurysm is a bulging of a blood vessel in the brain. Aneurysmal rupture affects 25,000 people each year and is associated with a 45% mortality rate. Therefore, it is critically important to treat cerebral aneurysms effectively before they rupture. Endovascular coiling is the most effective treatment for cerebral aneurysms. During coiling process, series of metallic coils are deployed into the aneurysmal sack with the intent of reaching a sufficient packing density (PD). Coils packing can facilitate thrombus formation and help seal off the aneurysm from circulation over time. While coiling is effective, high rates of treatment failure have been associated with basilar tip aneurysms (BTAs). Treatment failure may be related to geometrical features of the aneurysm. The purpose of this study was to investigate the influence of dome size, parent vessel (PV) angle, and PD on post-treatment aneurysmal hemodynamics using both computational fluid dynamics (CFD) and particle image velocimetry (PIV). Flows in four idealized BTA models with a combination of dome sizes and two different PV angles were simulated using CFD and then validated against PIV data. Percent reductions in post-treatment aneurysmal velocity and cross-neck (CN) flow as well as percent coverage of low wall shear stress (WSS) area were analyzed. In all models, aneurysmal velocity and CN flow decreased after coiling, while low WSS area increased. However, with increasing PD, further reductions were observed in aneurysmal velocity and CN flow, but minimal changes were observed in low WSS area. Overall, coil PD had the greatest impact while dome size has greater impact than PV angle on aneurysmal hemodynamics. These findings lead to a conclusion that combinations of treatment goals and geometric factor may play key roles in coil embolization treatment outcomes, and support that different treatment timing may be a critical factor in treatment optimization.
ContributorsIndahlastari, Aprinda (Author) / Frakes, David (Thesis advisor) / Chong, Brian (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the

Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Research on developing new algorithms to improve information on brain functionality and structure is ongoing. Studying neural activity through dipole source localization with electroencephalography (EEG) and magnetoencephalography (MEG) sensor measurements can lead to diagnosis and treatment of a brain disorder and can also identify the area of the brain from

Research on developing new algorithms to improve information on brain functionality and structure is ongoing. Studying neural activity through dipole source localization with electroencephalography (EEG) and magnetoencephalography (MEG) sensor measurements can lead to diagnosis and treatment of a brain disorder and can also identify the area of the brain from where the disorder has originated. Designing advanced localization algorithms that can adapt to environmental changes is considered a significant shift from manual diagnosis which is based on the knowledge and observation of the doctor, to an adaptive and improved brain disorder diagnosis as these algorithms can track activities that might not be noticed by the human eye. An important consideration of these localization algorithms, however, is to try and minimize the overall power consumption in order to improve the study and treatment of brain disorders. This thesis considers the problem of estimating dynamic parameters of neural dipole sources while minimizing the system's overall power consumption; this is achieved by minimizing the number of EEG/MEG measurements sensors without a loss in estimation performance accuracy. As the EEG/MEG measurements models are related non-linearity to the dipole source locations and moments, these dynamic parameters can be estimated using sequential Monte Carlo methods such as particle filtering. Due to the large number of sensors required to record EEG/MEG Measurements for use in the particle filter, over long period recordings, a large amounts of power is required for storage and transmission. In order to reduce the overall power consumption, two methods are proposed. The first method used the predicted mean square estimation error as the performance metric under the constraint of a maximum power consumption. The performance metric of the second method uses the distance between the location of the sensors and the location estimate of the dipole source at the previous time step; this sensor scheduling scheme results in maximizing the overall signal-to-noise ratio. The performance of both methods is demonstrated using simulated data, and both methods show that they can provide good estimation results with significant reduction in the number of activated sensors at each time step.
ContributorsMichael, Stefanos (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Kovvali, Narayan (Committee member) / Arizona State University (Publisher)
Created2012