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Description
Objective: Examine cardiovascular response to OMT via central and peripheral measurements. Methods: Central and peripheral cardiovascular signals of asymptomatic human subjects were monitored during a procedure with alternating rest and active phases. Active phases included systemic perturbations and application of controlled vertebral pressure (OMT) by an experienced osteopathic physician. Pulse plethysmograph and laser Doppler flow sensors measured peripheral flow from index and middle fingers bilaterally. A three-lead EKG monitored cardiac activity. The biosignals were recorded continuously, in real time, and analyzed in time and frequency domains. Results from the control group (n=11), without OMT, and active group (n=16), with OMT, were compared. Peripheral (n=5) and central responders (n=6), subsets of the active group showing stronger peripheral or central response, were examined. In an additional effort, a modified clinical device recorded spectral Doppler ultrasound signals of the radial and dorsalis pedis arteries of clinically asymptomatic human subjects. Controlled physiologic provocations (limb occlusion and elevation), were performed. Time domain and spectral analyses were completed. Results: In the human subject study, the time wave characteristics and spectral analysis resulted in similar trends. Peripheral blood flow attenuated in the control group over time, while it was maintained in the active group, and increased specifically during OMT in the responder groups. Heart rate remained around 65 BPM in the control group, fluctuated between 64-68 BPM in the active group, and dropped 4 and 3 BPM in the peripheral and central responder groups, respectively. The effect in the OMT group was statistically significant compared to no-OMT, however, was not statistically significant within-groups. For the preliminary spectral ultrasound Doppler study, segmental flow was successfully monitored. A prototype "Quick Assessment" tool was developed, providing instant post-processing results for clinical use. Conclusions: OMT along the vertebral column may influence autonomic processes that regulate heart rate and peripheral vascular flow.
ContributorsPedapati, Chandhana (Author) / Muthuswamy, Jitendra (Thesis advisor) / Makin, Inder (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Stroke is a leading cause of disability with varying effects across stroke survivors necessitating comprehensive approaches to rehabilitation. Interactive neurorehabilitation (INR) systems represent promising technological solutions that can provide an array of sensing, feedback and analysis tools which hold the potential to maximize clinical therapy as well as extend therapy to the home. Currently, there are a variety of approaches to INR design, which coupled with minimal large-scale clinical data, has led to a lack of cohesion in INR design. INR design presents an inherently complex space as these systems have multiple users including stroke survivors, therapists and designers, each with their own user experience needs. This dissertation proposes that comprehensive INR design, which can address this complex user space, requires and benefits from the application of interdisciplinary research that spans motor learning and interactive learning. A methodology for integrated and iterative design approaches to INR task experience, assessment, hardware, software and interactive training protocol design is proposed within the comprehensive example of design and implementation of a mixed reality rehabilitation system for minimally supervised environments. This system was tested with eight stroke survivors who showed promising results in both functional and movement quality improvement. The results of testing the system with stroke survivors as well as observing user experiences will be presented along with suggested improvements to the proposed design methodology. This integrative design methodology is proposed to have benefit for not only comprehensive INR design but also complex interactive system design in general.
ContributorsBaran, Michael (Author) / Rikakis, Thanassis (Thesis advisor) / Olson, Loren (Thesis advisor) / Wolf, Steven L. (Committee member) / Ingalls, Todd (Committee member) / Arizona State University (Publisher)
Created2014
Description
Alzheimer's disease (AD) is the most common form of dementia leading to cognitive dysfunction and memory loss as well as emotional and behavioral disorders. It is the 6th leading cause of death in United States, and the only one among top 10 death causes that cannot be prevented, cured or slowed. An estimated 5.4 million Americans live with AD, and this number is expected to triple by year 2050 as the baby boomers age. The cost of care for AD in the US is about $200 billion each year. Unfortunately, in addition to the lack of an effective treatment or AD, there is also a lack of an effective diagnosis, particularly an early diagnosis which would enable treatment to begin before significant neuronal damage has occurred.
Increasing evidence implicates soluble oligomeric forms of beta-amyloid and tau in the onset and progression of AD. While many studies have focused on beta-amyloid, soluble oligomeric tau species may also play an important role in AD pathogenesis. Antibodies that selectively identify and target specific oligomeric tau variants would be valuable tools for both diagnostic and therapeutic applications and also to study the etiology of AD and other neurodegenerative diseases.
Recombinant human tau (rhTau) in monomeric, dimeric, trimeric and fibrillar forms were synthesized and purified to perform LDH assay on human neuroblastoma cells, so that trimeric but not monomeric or dimeric rhTau was identified as extracellularly neurotoxic to neuronal cells. A novel biopanning protocol was designed based on phage display technique and atomic force microscopy (AFM), and used to isolate single chain antibody variable domain fragments (scFvs) that selectively recognize the toxic tau oligomers. These scFvs selectively bind tau variants in brain tissue of human AD patients and AD-related tau transgenic rodent models and have potential value as early diagnostic biomarkers for AD and as potential therapeutics to selectively target toxic tau aggregates.
Increasing evidence implicates soluble oligomeric forms of beta-amyloid and tau in the onset and progression of AD. While many studies have focused on beta-amyloid, soluble oligomeric tau species may also play an important role in AD pathogenesis. Antibodies that selectively identify and target specific oligomeric tau variants would be valuable tools for both diagnostic and therapeutic applications and also to study the etiology of AD and other neurodegenerative diseases.
Recombinant human tau (rhTau) in monomeric, dimeric, trimeric and fibrillar forms were synthesized and purified to perform LDH assay on human neuroblastoma cells, so that trimeric but not monomeric or dimeric rhTau was identified as extracellularly neurotoxic to neuronal cells. A novel biopanning protocol was designed based on phage display technique and atomic force microscopy (AFM), and used to isolate single chain antibody variable domain fragments (scFvs) that selectively recognize the toxic tau oligomers. These scFvs selectively bind tau variants in brain tissue of human AD patients and AD-related tau transgenic rodent models and have potential value as early diagnostic biomarkers for AD and as potential therapeutics to selectively target toxic tau aggregates.
ContributorsTian, Huilai (Author) / Sierks, Michael R (Thesis advisor) / Dai, Lenore (Committee member) / Tillery, Stephen H (Committee member) / Nielsen, David R (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2014
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 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
Description
In this work, a novel method is developed for making nano- and micro- fibrous hydrogels capable of preventing the rejection of implanted materials. This is achieved by either (1) mimicking the native cellular environment, to exert fine control over the cellular response or (2) acting as a protective barrier, to camouflage the foreign nature of a material and evade recognition by the immune system. Comprehensive characterization and in vitro studies described here provide a foundation for developing substrates for use in clinical applications. Hydrogel dextran and poly(acrylic acid) (PAA) fibers are formed via electrospinning, in sizes ranging from nanometers to microns in diameter. While "as-electrospun" fibers are continuous in length, sonication is used to fragment fibers into short fiber "bristles" and generate nano- and micro- fibrous surface coatings over a wide range of topographies. Dex-PAA fibrous surfaces are chemically modified, and then optimized and characterized for non-fouling and ECM-mimetic properties. The non-fouling nature of fibers is verified, and cell culture studies show differential responses dependent upon chemical, topographical and mechanical properties. Dex-PAA fibers are advantageously unique in that (1) a fine degree of control is possible over three significant parameters critical for modifying cellular response: topography, chemistry and mechanical properties, over a range emulating that of native cellular environments, (2) the innate nature of the material is non-fouling, providing an inert background for adding back specific bioactive functionality, and (3) the fibers can be applied as a surface coating or comprise the scaffold itself. This is the first reported work of dex-PAA hydrogel fibers formed via electrospinning and thermal cross-linking, and unique to this method, no toxic solvents or cross-linking agents are needed to create hydrogels or for surface attachment. This is also the first reported work of using sonication to fragment electrospun hydrogel fibers, and in which surface coatings were made via simple electrostatic interaction and dehydration. These versatile features enable fibrous surface coatings to be applied to virtually any material. Results of this research broadly impact the design of biomaterials which contact cells in the body by directing the consequent cell-material interaction.
ContributorsLouie, Katherine BoYook (Author) / Massia, Stephen P (Thesis advisor) / Bennett, Kevin (Committee member) / Garcia, Antonio (Committee member) / Pauken, Christine (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2011
Description
In this thesis, I present a lab-on-a-chip (LOC) that can separate and detect Escherichia Coli (E. coli) in simulated urine samples for Urinary Tract Infection (UTI) diagnosis. The LOC consists of two (concentration and sensing) chambers connected in series and an integrated impedance detector. The two-chamber approach is designed to reduce the non-specific absorption of proteins, e.g. albumin, that potentially co-exist with E. coli in urine. I directly separate E. coli K-12 from a urine cocktail in a concentration chamber containing micro-sized magnetic beads (5 µm in diameter) conjugated with anti-E. coli antibodies. The immobilized E. coli are transferred to a sensing chamber for the impedance measurement. The measurement at the concentration chamber suffers from non-specific absorption of albumin on the gold electrode, which may lead to a false positive response. By contrast, the measured impedance at the sensing chamber shows ~60 kÙ impedance change between 6.4x104 and 6.4x105 CFU/mL, covering the threshold of UTI (105 CFU/mL). The sensitivity of the LOC for detecting E. coli is characterized to be at least 3.4x104 CFU/mL. I also characterized the LOC for different age groups and white blood cell spiked samples. These preliminary data show promising potential for application in portable LOC devices for UTI detection.
ContributorsKim, Sangpyeong (Author) / Chae, Junseok (Thesis advisor) / Phillips, Stephen M. (Committee member) / Blain Christen, Jennifer M. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Biological membranes are critical to cell sustainability by selectively permeating polar molecules into the intracellular space and providing protection to the interior organelles. Biomimetic membranes (model cell membranes) are often used to fundamentally study the lipid bilayer backbone structure of the biological membrane. Lipid bilayer membranes are often supported using inorganic materials in an effort to improve membrane stability and for application to novel biosensing platforms. Published literature has shown that a variety of dense inorganic materials with various surface properties have been investigated for the study of biomimetic membranes. However, literature does not adequately address the effect of porous materials or supports with varying macroscopic geometries on lipid bilayer membrane behavior. The objective of this dissertation is to present a fundamental study on the synthesis of lipid bilayer membranes supported by novel inorganic supports in an effort to expand the number of available supports for biosensing technology. There are two fundamental areas covered including: (1) synthesis of lipid bilayer membranes on porous inorganic materials and (2) synthesis and characterization of cylindrically supported lipid bilayer membranes. The lipid bilayer membrane formation behavior on various porous supports was studied via direct mass adsorption using a quartz crystal microbalance. Experimental results demonstrate significantly different membrane formation behaviors on the porous inorganic supports. A lipid bilayer membrane structure was formed only on SiO2 based surfaces (dense SiO2 and silicalite, basic conditions) and gamma-alumina (acidic conditions). Vesicle monolayer adsorption was observed on gamma-alumina (basic conditions), and yttria stabilized zirconia (YSZ) of varying roughness. Parameters such as buffer pH, surface chemistry and surface roughness were found to have a significant impact on the vesicle adsorption kinetics. Experimental and modeling work was conducted to study formation and characterization of cylindrically supported lipid bilayer membranes. A novel sensing technique (long-period fiber grating refractometry) was utilized to measure the formation mechanism of lipid bilayer membranes on an optical fiber. It was found that the membrane formation kinetics on the fiber was similar to its planar SiO2 counterpart. Fluorescence measurements verified membrane transport behavior and found that characterization artifacts affected the measured transport behavior.
ContributorsEggen, Carrie (Author) / Lin, Jerry Y.S. (Thesis advisor) / Dai, Lenore (Committee member) / Rege, Kaushal (Committee member) / Thornton, Trevor (Committee member) / Vogt, Bryan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Interictal spikes, together with seizures, have been recognized as the two hallmarks of epilepsy, a brain disorder that 1% of the world's population suffers from. Even though the presence of spikes in brain's electromagnetic activity has diagnostic value, their dynamics are still elusive. It was an objective of this dissertation to formulate a mathematical framework within which the dynamics of interictal spikes could be thoroughly investigated. A new epileptic spike detection algorithm was developed by employing data adaptive morphological filters. The performance of the spike detection algorithm was favorably compared with others in the literature. A novel spike spatial synchronization measure was developed and tested on coupled spiking neuron models. Application of this measure to individual epileptic spikes in EEG from patients with temporal lobe epilepsy revealed long-term trends of increase in synchronization between pairs of brain sites before seizures and desynchronization after seizures, in the same patient as well as across patients, thus supporting the hypothesis that seizures may occur to break (reset) the abnormal spike synchronization in the brain network. Furthermore, based on these results, a separate spatial analysis of spike rates was conducted that shed light onto conflicting results in the literature about variability of spike rate before and after seizure. The ability to automatically classify seizures into clinical and subclinical was a result of the above findings. A novel method for epileptogenic focus localization from interictal periods based on spike occurrences was also devised, combining concepts from graph theory, like eigenvector centrality, and the developed spike synchronization measure, and tested very favorably against the utilized gold rule in clinical practice for focus localization from seizures onset. Finally, in another application of resetting of brain dynamics at seizures, it was shown that it is possible to differentiate with a high accuracy between patients with epileptic seizures (ES) and patients with psychogenic nonepileptic seizures (PNES). The above studies of spike dynamics have elucidated many unknown aspects of ictogenesis and it is expected to significantly contribute to further understanding of the basic mechanisms that lead to seizures, the diagnosis and treatment of epilepsy.
ContributorsKrishnan, Balu (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Kostantinos (Committee member) / Spanias, Andreas (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2012
Description
There is a tremendous need for wireless biological signals acquisition for the microelectrode-based neural interface to reduce the mechanical impacts introduced by wire-interconnects system. Long wire connections impede the ability to continuously record the neural signal for chronic application from the rodent's brain. Furthermore, connecting and/or disconnecting Omnetics interconnects often introduces mechanical stress which causes blood vessel to rupture and leads to trauma to the brain tissue. Following the initial implantation trauma, glial tissue formation around the microelectrode and may possibly lead to the microelectrode signal degradation. The aim of this project is to design, develop, and test a compact and power efficient integrated system (IS) that is able to (a) wirelessly transmit triggering signal from the computer to the signal generator which supplies voltage waveforms that move the MEMS microelectrodes, (b) wirelessly transmit neural data from the brain to the external computer, and (c) provide an electrical interface for a closed loop control to continuously move the microelectrode till a proper quality of neural signal is achieved. One of the main challenges of this project is the limited data transmission rate of the commercially available wireless system to transmit 400 kbps of digitized neural signals/electrode, which include spikes, local field potential (LFP), and noise. A commercially available Bluetooth module is only capable to transmit at a total of 115 kbps data transfer rate. The approach to this challenge is to digitize the analog neural signal with a lower accuracy ADC to lower the data rate, so that is reasonable to wirelessly transfer neural data of one channel. In addition, due to the limited space and weight bearing capability to the rodent's head, a compact and power efficient integrated system is needed to reduce the packaged volume and power consumption. 3D SoP technology has been used to stack the PCBs in a 3D form-factor, proper routing designs and techniques are implemented to reduce the electrical routing resistances and the parasitic RC delay. It is expected that this 3D design will reduce the power consumption significantly in comparison to the 2D one. The progress of this project is divided into three different phases, which can be outlined as follow: a) Design, develop, and test Bluetooth wireless system to transmit the triggering signal from the computer to the signal generator. The system is designed for three moveable microelectrodes. b) Design, develop, and test Bluetooth wireless system to wirelessly transmit an amplified (200 gain) neural signal from one single electrode to an external computer. c) Design, develop, and test a closed loop control system that continuously moves a microelectrode in searching of an acceptable quality of neural spikes. The outcome of this project can be used not only for the need of neural application but also for a wider and general applications that requires customized signal generations and wireless data transmission.
ContributorsZhou, Li (Author) / Muthuswamy, Jitendran (Thesis advisor) / Sutanto, Jemmy (Thesis advisor) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2012
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