Department: Biomedical Engineering ![[clear]](close-x.png "Remove this limiter")
89 matches in the database.
These are records: 1 - 30.
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1.
Algaze, Antonio.
Characterization of the Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging Response in Amblyopia.
Degree: PhD, Biomedical Engineering, 2002, Ohio State University
► Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (FMRI) was implemented…
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▼ Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (FMRI) was implemented at 1.5 Tesla to characterize visual cortex activation patterns in human amblyopia. The dissertation consists of three main components. First, the voxel-wise repeatability of visual cortex FMRI results was assessed using a mixed-effects ANOVA group analysis. Two stimuli were presented monocularly and binocularly to ten subjects in two independent scanning sessions. Visual cortex activation maps were found to be repeatable regardless of the stimulus type or eye stimulated. The second study investigated interocular differences in the level and extent of activation in amblyopic and normal subjects. Five amblyopes and six normals were recruited. Stimuli included a homogeneous flickering field (8 Hz) and counterphasing (8 Hz) vertical sinusoidal gratings at 0.5, 1 and 2 cpd. Amblyopes exhibited a larger (P<0.05) interocular activation difference compared to normals. Dominant eye stimulation was found to elicit a stronger BOLD response and larger extent of activation in the visual cortex compared to the amblyopic eye. In summary, FMRI was found to be sensitive to amblyopia-related deficits in the human visual cortex and, hence, has potential for basic amblyopia research. The third study investigated the effects of levodopa (L-dopa) on the level and extent of visual cortex activation. Six amblyopes and nine normals were recruited. A baseline FMRI session was followed by a second session 90 minutes after L-dopa. Visual stimuli included counterphased (4 Hz) vertical sinusoidal gratings at 1 and 2 cpd. The FMRI response was characterized by the total volume and the average level of activation. An interocular absolute difference (IAD) was defined in terms of said measures for between-population analysis of monocular data. After L-dopa, visual acuity improved significantly (P=0.03) in the amblyopic eye. The FMRI response to L-dopa was population-specific, as indicated by a treatment-by-population interaction for the volume of activation IAD (P=0.018), as well as for the volume (P=0.026) and level (P=0.043) of activation elicited by binocular stimulation. Furthermore, a significant (P<0.05) decrease in the volume of activation was found exclusively for the amblyopic eye after L-dopa, in spite of improvement in visual acuity.
Advisors/Committee Members: Roberts, Cynthia.
Subjects: Engineering, Biomedical
Keywords: BOLD; FMRI; AMBLYOPIA; VISUAL CORTEX; REPEATABILITY; L-DOPA
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2.
Apaydin, Elif.
Microfabrication Techniques for Printing on PDMS Elastomers for Antenna and Biomedical Applications.
Degree: PhD, Biomedical Engineering, 2009, Ohio State University
► The demand for flexible substrates in the electronics industry and medicine has…
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▼ The demand for flexible substrates in the electronics industry and medicine has highlighted the importance of applicable printing techniques on these materials. Neural prosthetics interfacing with soft tissues and tight packaging requirements in the high-frequency electronics field require application-specific fabrication methodologies for printing conductors on or embedded in flexible substrates. The purpose of this dissertation is to introduce novel fabrication techniques for printing metal patterns on silicone elastomers. In pursuing this goal, two applications in the biomedical and antennas fields are given. These applications require printing of metals on silicone elastomers and the requirements of these applications are met with application-specific microfabrication processes. The initial project involves printing microwave structures on PDMS-ceramic composites. These structures include transmission lines, a patch antenna and a feeding pattern for a GPS antenna. The second work requires the fabrication of a microelectrode array for recording neural signals from the brain cortex surface. Microfabrication techniques have been developed for the device fabrications. In the first application, a novel technique for direct printing of patterned conducting geometries on silicone-based, flexible polymer composites is presented. Specifically, micro-texturing is applied on the polymer composite surface followed by evaporation of a buffer titanium layer and a seed layer of copper. Electroplating is also applied as a final step to increase conductor layer thickness to accommodate polymer layer bending while maintaining good RF conductivity. The printed examples include 5 mm wide copper microstrip lines on polymer composite substrates. These printed microstrip lines demonstrated very low sheet resistivity of 0.1 ohm per square for frequencies up to several GHz. They were also shown to maintain low resistance during large bending deformations. To investigate RF performance, a patch antenna was also printed on a polymer-ceramic composite and shown to perform as predicted. Apart from patch antenna, a more complex patterned microwave structure that is a hybrid feeding structure of a GPS antenna has been fabricated. The performance evaluation of this hybrid feeding is in accordance with the simulated results and demonstrates the working fabrication process. In the second application, the neural microelectrode has been fabricated based on a silicone elastomer substrate with an array of three-dimensional platinum contacts as the recording sites. Platinum contacts are exposed on the elastomer surface and these recording sites are embedded in elastomer, forming a robust three-dimensional structure suitable for surface recording. This robust yet flexible device is fabricated with microfabrication techniques including evaporation, photolithography, wet etching, electroplating and welding. Cytocompatibility of the device was tested with mouse fibroblasts and mouse forebrain neurons. The cell viability results verify the cytocompatibility of the fabricated device. The electrical characteristics of the electrodes were demonstrated with impedance measurements.
Advisors/Committee Members: Hansford, Derek.
Subjects: Engineering
Keywords: Microfabrication Techniques; Flexible electronics; PDMS elastomers; Patterned Metal Printing; Microtextured Surface; Flexible Antennas; Flexible Neural Microelectrode Array; Brain Cortical Surface Recording; Pt Electroplating; Cu Electroplating
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3.
Barnes, Phillip D.
Initial Study of Anisotropic Textures for Identification of Blood Vessels in 7T MRI Brain Phase Images.
Degree: PhD, Biomedical Engineering, 2010, Ohio State University
► Within medical science, pattern recognition is the basis for computer-aided diagnosis (CAD),…
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▼ Within medical science, pattern recognition is the basis for computer-aided diagnosis (CAD), which assists doctors (in particular radiologists) in the interpretation of medical images, whose quality and usefulness are constantly evolving. Modern magnetic resonance imaging (MRI) scans can provide information about subvoxel anatomical structures (e.g. microvessels) that may not be specifically resolvable within a given image set. Hence, subvoxel anatomical structures within a given image may not be readily apparent to the observer (i.e. radiologist); nevertheless, their presence may be detected through their statistical relationship with their surrounding voxels. Such statistical relationships can be characterized by texture features. The goal of this research dissertation is to investigate the feasibility of using anisotropic texture features for the identification of blood vessels that may not be specifically resolvable in the image datasets. Such features can be used as the basis for the feature extraction component of a complete pattern recognition system for the purpose of automatically identifying blood vessels in the human brain. The approach of this project is to apply 2D statistical texture features as inputs to a classifier (such as a neural network) to analyze MRI images. The specific aims of this dissertation are: a) to provide a set of texture features extracted from 7T MRI human brain phase images that demonstrate the ability to characterize the presence of underlying microvessel structures; b) to provide a classifier, in particular a neural network architecture that makes use of the extracted features; and c) to evaluate the performance of the feature-classifier combination. The results of this research demonstrated the feature-classifier combination exhibit reasonably well generalization across the testing data, and suggest it may be possible for a computer to discriminate hidden vessels not detectable by human observers.
Advisors/Committee Members: Clymer, Bradley.
Subjects: Biomedical research
Keywords: phase images, texture analysis, anisotropy, 7T brain images, anisotropic texture features, blood vessel identification
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4.
Barnes, Phillip Deshawn.
Protein deployment onto a model field effect transistor silicon dioxide sensing surface.
Degree: MS, Biomedical Engineering, 2004, Ohio State University
► Biosensors are analytical devices, which convert biological interactions into electrical signals. Biosensors…
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▼ Biosensors are analytical devices, which convert biological interactions into electrical signals. Biosensors based on field effect transistor (FET) architecture, or semiconductor biosensors, in general, are representative of the merger between molecular biology and electronics. A novel modification to existing FET biosensors, called the pH-modulation FET sensor is in its developmental stage. In common with previous FET biosensors, biological analytes bind specifically to a FET channel coated with biological affinity reagents (peptides and antibodies) and induce a local charge transfer changing the FET conductance. Our design allows extraction of additional analytical information from the bound analyte. By controlled manipulation of channel pH, multiple charge parameters determined by the analyte's primary amino acid sequence are examined. Observation and measurement of the charge transfer at various pHs is expected to result in a signature that can be compared to a reference profile for a specific analyte. In principal, the strategy should increase sensitivity and decrease error rates.There are several steps to realize the proposed sensor. This thesis focuses on one of them, the issue of optimizing conditions for protein deployment on the sensing channel of the device. For this purpose a model system was generated, which used diced silicon dioxide wafers to mimic the gate oxidation step of actual FET channel, and used streptavidin-biotin interactions as the model detection system. The first series of experiments used direct-physical absorption to deploy streptavidin onto diced silicon dioxide chips, using enzyme linked immunosorbent assay (ELISA) and fluorescence microscopy for analysis. The results indicated that little streptavidin bound to the "flat" regions of the silicon dioxide surface, but seem to preferentially bind to its edges and surface asperities.The second series of experiments used a focused ion beam to produce well-defined patterns into a silicon dioxide chip surface. This series of experiments still used direct-physical absorption for protein deposition, and atomic force microscopy and fluorescence microscopy for analysis. The results at first seemed to suggest physical texturing of the silicon dioxide surface promoted preferential protein binding, but upon further examination the findings were inclusive, and streptavidin was observed to be weakly bound to the silicon dioxide surface. The results from the first two rounds of experiments suggested that direct-physical absorption would not be a sufficient method of deploying protein for the final device.The third and final round of experiments employed a silane to "functionalize" the silicon dioxide surface, and used ELISA for analysis. The results indicated that silanized surfaces, with its covalent bonds, bound streptavidin to the silicon dioxide surface with more consistency, reliability, and stability than direct-physical absorption, thus suggest its use in the final device for protein deployment.
Advisors/Committee Members: Lee, Stephen C.
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5.
Bednarski Spiwak, Allison Joan.
Fatigue of Polymers in the Roller Head Raceway of Extracorporeal Circuits.
Degree: PhD, Biomedical Engineering, 2008, Ohio State University
► Polyvinyl chloride (PVC) is a brittle amorphous polymer, but processing the PVC…
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▼ Polyvinyl chloride (PVC) is a brittle amorphous polymer, but processing the PVC with plasticizer results in a flexible material able to form non-rigid tubing. Plasticized PVC (pPVC) is available in medical grade products for use in extracorporeal drug and fluid delivery. There are known complications including plasticizer loss, drug interactions, spallation and raceway rupture associated with this product when used in the roller pump of the cardiopulmonary bypass circuit.This is pioneering research that studies tubing fatigued by use in the roller head raceway. The hypothesis states pPVC tubing exposed to the roller head raceway in a system simulating cardiopulmonary bypass changes material properties for tensile strength, elastic modulus and elongation. An additional hypothesis states spallation is recognized continually during compression in the roller head raceway and occurs at multiple surfaces of the tubing inner lumen. Better evaluation of polymers approved and chosen for the specific medical application of extracorporeal circulation by the roller head raceway and other approved devices will be obtained through this research protocol. With this basic knowledge clinicians will better understand the product selections available and better understand how to evaluate material offered from the manufacturers for specific applications. Minimal research recognizes the basic science of spallation and catastrophic rupture that occur during cardiopulmonary bypass. Cardiopulmonary bypass material selection was made to alleviate these concerns including the switch to pPVC from other non-rigid polymers, such as silicone and natural rubber. PVC is known to have a complicated morphology unstable during the compression in the roller head raceway. The initial phase of the study will trend the change in mechanical behavior of the polymer tubing after exposure to fatigue stresses of cyclic bending and compression by the roller head contact. This includes mimicking set-up and priming techniques used to prepare the equipment for patient care. Physiological saline and lipid will be used to duplicate the blood interaction with the pPVC known to influence material chemical stability. Pump settings for occlusion and RPM will simulate clinical cardiopulmonary bypass protocols. The material takes on a more crystalline structure leading to changes in the performance of the pPVC material. This simulation will develop the knowledge to understand the changes in behavior experienced during a typical cardiac surgical procedure.
Advisors/Committee Members: Hansford, Derek.
Subjects: Engineering
Keywords: plasticized poly(vinyl chloride); cardiopulmonary bypass; extracorporeal circulation; fatigue; roller head raceway
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6.
Bluestein, Katharine T.
Inversion Recovery Sequences for the Detection of Cortical Lesions in Multiple Sclerosis Using a 7 Tesla MR Imaging System.
Degree: PhD, Biomedical Engineering, 2012, Ohio State University
► Although white matter lesions have been the target of a majority of…
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▼ Although white matter lesions have been the target of a majority of research in multiple sclerosis imaging, they have been shown to have little correlation to the symptoms that multiple sclerosis patients experience as the disease progresses. Due to their small size and low tissue contrast in images, cortical lesions have only recently been implicated in the disease process and have been shown to be numerous in the later stages of disease. This work uses ultrahigh field 7 Tesla MRI capable of high image resolution and greater tissue contrast to develop an imaging protocol for cortical lesion detection in vivo. Using an inversion recovery turbo field echo sequence, white matter attenuation is shown to provide good cortical lesion and excellent white matter lesion detection. Other inversion recovery contrast options are explored as well. Related topics are discussed, such as the contributions to the logistic regression model for lesion detection, the process for training new readers in cortical lesion detection, and finally, a novel use of the gray matter attenuated inversion recovery contrast option is shown to potentially provide insight on the severity of tissue destruction in white matter lesions. With these project components, inversion recovery is optimized for cortical lesion detecion at 7 Tesla to improve disease diagnostics and treatment monitoring.
Advisors/Committee Members: Schmalbrock, Petra.
Subjects: Radiology
Keywords: multiple sclerosis, cortical lesions, white matter lesions, MRI, 7 Tesla
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7.
Bolte, John Henry IV.
Injury and impact response of the shoulder due to lateral and oblique loading.
Degree: PhD, Biomedical Engineering, 2004, Ohio State University
► It has been shown in side impact automobile accidents that the shoulder…
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▼ It has been shown in side impact automobile accidents that the shoulder is the point of first contact with the intruding door, causing large forces to be carried by the shoulder complex and, upon failure, into the thorax of the occupant. Shoulder kinematics and the distribution of load through the shoulder girdle are well documented for every day functions; however, the response of the shoulder to impact and the transmission of load to the thorax under high-energy impact are not well understood. The mechanical response, or stiffness properties, of the shoulder that would be helpful in future dummy development is also not known. The shoulder response under the oblique loading that occurs when the intruding door does not strike in a purely lateral manner is unknown. The response of the shoulder to impact and the protective relationship between the shoulder girdle and the thorax is critical to understanding human response to lateral impact and to developing countermeasures to prevent and mitigate thoracic, as well as shoulder, trauma. The purpose of this study was to define injury criteria for the shoulder, define the stiffness of the shoulder in response to both lateral and oblique loading, and investigate the protective relationship between the shoulder girdle and the thorax. This study was conducted in two separate phases. Phase I of the research was comprised of 24 lateral shoulder impacts. Phase II included 14 lateral and oblique shoulder impacts. Of the 14 tests, four of them were conducted lateral to the shoulder along the subject’s y-axis, four of them were conducted 15° anterior to this axis, and six were conducted 30° anterior to the subject’s y-axis. All of the testing utilized a pneumatic ram to impact the shoulders of post-mortem human subjects (PMHSs) at the level of the glenohumeral joint. The first thoracic vertebrae and both shoulders of the subject were instrumented with tri-axial linear accelerometers on the sternum, clavicle, acromion process, and inferior angle of the scapula. The impacting mass was instrumented with an accelerometer and displacement transducer. In addition to this instrumentation, the tests were documented by high-speed digital imagery. Radiographs (x-rays), magnetic resonance images (MRIs), and autopsies were used to document injury to the subjects. The results from the two phases of testing revealed differences between the stiffness of the shoulder when loaded laterally to that when it is loaded obliquely. The shoulder was found to deflect more medially when loaded obliquely then when it is loaded laterally. This can be attributed to the ability of the scapula to slide posteriorly around the thoracic cage. The ability of the shoulder to displace medially while simultaneously deflecting posteriorly in oblique impact is important to replicate in the ATDs because it results in the load being transmitted to the upper thoracic cage.
Advisors/Committee Members: Litsky, Alan.
Subjects: Engineering, Biomedical
Keywords: Shoulder, Biomechanics, Lateral, Oblique, Impacts, Cadaver, Injury Criteria, Stiffness Corridor
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8.
Brush, Ursula Jane.
Design and Validation of an Intensity-Based POF Bend Sensor Applications in Measuring Three-Dimensional Trunk Motion.
Degree: MS, Biomedical Engineering, 2010, Ohio State University
► Many efforts have been put forth to better understand proper trunk posture…
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▼ Many efforts have been put forth to better understand proper trunk posture while in motion. Such efforts include wearable devices such as the Lumbar Motion Monitor that track the three dimensional motion of the trunk over time.37 Often these devices are prohibitively expensive, heavy, and cumbersome for subjects attempting to move naturally for sports or biomechanics research. Recent developments in plastic optical fiber (POF) quality have made it possible to build an inexpensive bend sensor for applications in measuring trunk motion on the job.6 An intensity-based POF bend sensor is not only lightweight, noninvasive, and simple to build, but provides a signal with almost no processing requirements. The purpose of this thesis is to fabricate an inexpensive, wearable POF bend sensor suitable for dynamic motion and to test its use for recording the three-dimensional motion of the trunk. The fabrication of a POF bend sensor vest is described as well as its validation with a Vicon passive optical motion capture system. Overall, the lateral and sagittal vest data correlated with the Vicon system to within ±3.8° of average curvature or 11.5% or less of the total range of motion for each dimension. While jogging RMS error increased to ±6.7° when compared to the Vicon system, the average range of motion captured from the vest correlated to within ±2.2° of the Vicon range of motion data. Preliminary work was also accomplished for twisting motion with an average percent RMS error of 13.2% for range of motion trials. Considering the low-cost and non-invasive nature of the POF bend sensor, these results show promise for using this sensor in a variety of applications. These applications include feedback monitoring of motion for injury prevention or sports performance or for assessment of lifting techniques in the workplace. Future work would involve characterizing the reliability of the sensor over long periods of time as well as capturing all three dimensions of motion simultaneously.
Advisors/Committee Members: Chaudhari, Ajit.
Subjects: Biomedical research; Engineering
Keywords: motion capture; biomechanics; posture; plastic optical fiber
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9.
Burgess, Richard Ely.
Magnetic resonance imaging at ultra high field: implications for human neuroimaging.
Degree: PhD, Biomedical Engineering, 2004, Ohio State University
► Even before the development of magnetic resonance imaging, scientists and engineers repeatedly…
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▼ Even before the development of magnetic resonance imaging, scientists and engineers repeatedly predicted that, despite the theoretical potential of high field, physical and engineering challenges would prevent the practical realization of gains in signal to noise. Many of the arguments used to disparage high field MRI can be divided into issues of uniform excitation, image distortion, and patient safety. In the former category lies challenges such as RF penetration limitations, dielectric resonances, coil self-resonance, coil-sample interactions, and RF power requirements, which may prevent uniform B1 can best be studied with numerical modeling techniques. Within the second category are effects such as chemical shift artifact, susceptibility distortions, and contrast convergence that can be well studied through analytic techniques and methodical manipulation of imaging parameters. In the category of safety belong RF power deposition and magnetohydrodynamic effects. In this thesis, issues of static field safety will be exhaustively explored and investigation of image contrast and quality will be undertaken to assess the potential of the 8 Tesla system for human neuroimaging. This thesis will specifically examine the theoretical risk of cardiac arrhythmia from induced currents and demonstrate the negligible cardiac, cognitive, and physiological bioeffects through animal and human studies. The extent of signal to noise ratio enhancement possible at 8 Tesla will be assessed and harnessed to obtain high resolution whole brain images. In the end, experimental results and analysis show that, despite the presence of artifact, high resolution images of the human brain with unique contrast can be safely obtained at 8 Tesla.
Advisors/Committee Members: Robitaille, Pierre-Marie Luc.
Keywords: magnetic resonance; magnetic resonance imaging; MRI; high field; 8 tesla; high resolution
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10.
Butt, Omar Iqbal.
Regulation of biomechanical properties of cells in circulation by angiotensin II.
Degree: PhD, Biomedical Engineering, 2006, Ohio State University
► Angiotensin II (ATII) is an important growth factor for many cell types…
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▼ Angiotensin II (ATII) is an important growth factor for many cell types including endothelial, muscular and renal cells and also acts as a key promoter of certain cardiovascular diseases. Recently, ATII has also been shown to regulate angiogenesis and vasculogenesis. Its signaling mechanism includes formation of reactive oxygen species (ROS), which are the turning plate of many cellular processes, including the regulation of cell volume. This study looks at the acute effects of ATII treatment on biomechanical properties of cells in circulation including monocytes and endothelial progenitor cells (EPC). Since these biomechanical factors are crucial in the onset of disease and vasculogenesis, we look at how ATII regulates properties such as volume, filterability and adherence. Methods - This research involved the use of human THP-1 cells, an embryonic mouse pulmonary endothelial progenitor cell line, MFLM4, and a primary cell line of endothelial progenitors, CD117 positive cells, and their acute biomechanical response to ATII. Various techniques were used to measure volume, filterability, and adherence of these cells. Results - The treatment with ATII induced an increase in the pulmonary EPC volume up to about 10%. Time course indicated an acute increase in the volume, with a maximum at 10 µM ATII and at 20 minutes, and then a slow decrease back towards the original cell volume. The process was blocked by the ATII receptor type 1 inhibitor losartan, indicating an involvement of the AT1 receptor subtype in the process. ATII induced the formation of ROS, and a redistribution of F-actin from an intracellular to a cortical pool. MnTMPyP, a superoxide dismutase inhibitor, blocked the increase in volume of the cells. A similar effect was seen with NADPH oxidase inhibitor diphenyleneiodonium (DPI). The combination of the SOD mimetic and DPI indicated NAD(P)H oxidase-derived ROS mediated cell volume regulation. Conclusion - We detected a novel effect of angiotensin II on the biomechanics (volume, surface features, and filterability) of cells in circulation, mainly monocytes and endothelial progenitor cells, which is cell-, factor-, and ROS-dependent. These data predict an in vivo behavior of EPC in angiogenic settings that depends on their phenotypes
Advisors/Committee Members: Moldovan, Nicanor I.
Subjects: Biology, Cell
Keywords: Angiotensin II (ATII); cell volume; filterability; reactive oxygen species
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11.
Casal, Patricia.
Detection of Protein Analytes in Physiologic Environments via Planar ImmunoHFET.
Degree: PhD, Biomedical Engineering, 2012, Ohio State University
► Electrochemical detection of protein binding in physiological salt concentration environments by planar…
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▼ Electrochemical detection of protein binding in physiological salt concentration environments by planar field effect transistor (FET) platforms has not previously been convincingly presented. Historically, the use of immunologically modified FET sensors (immunoFETs) for in vivo detection of proteins has been dismissed as infeasible due to assumptions about charge shielding and Debye length constraints. These assumptions, and others, are misconceptions and do not accurately represent what is known immunologically about proteins and antibodies. In this work, the flaws of the classical analysis, approaches for addressing this model and demonstrating feasibility of immunoFET sensing in physiologic environments are discussed and proposed. Successful detection of multiple, distinct analytes by an AlGaN heterojunction immunoFET are then reported and discussed. Approached for improving sensitivity of the device are also discussed. A key parameter in device sensitivity and function is the overall distance between bound analyte and the semiconductor. Consequently, differential properties of surface polymers and surface receptors are design parameters for FET sensors. Thickness, adhesion and wear of silane polymer layers bound to surface Al2O3 oxides are compared. These properties of the film after additional deposition of biotin and streptavidin are further compared. Consistent differences in thickness and wear resistance of silane films that can be correlated to film chemistry and deposition procedures are reported and discussed. Improved interfacial properties of immunoHFETs and incorporation of a control gate into AlGaN device architecture result in improved immunoHFET sensitivity. Genuine immunoFETs which detect binding of multiple, distinct analytes (huCXCL9, muCXCL9, CXCL10, CCL5 and streptavidin) in physiologic buffer containing high levels of salt (150mM NaCl) are reported. Additionally detection of huCXCL9 and huCXCL10 in murine serum is presented using the immunoHFET platform. The immunoHFETs reported are functionalized with polyclonal intact anti-analyte IgG antibodies. These results provide unequivocal proof of the feasibility of immunoHFETs operating in physiological environments, in direct contradiction of the classical assessment of immunoFET feasibility. This demonstrates the need for critical reconsideration of the classical assessment, but also the need and desirability of developing immunoFETs for clinical applications.
Advisors/Committee Members: Lee, Stephen.
Subjects: Biomedical Engineering; Engineering; Immunology
Keywords: immunoFET; protein sensor; biosensor; transplant rejection; field effect transistor
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12.
Chakrapani, Aravind.
Processing and characterization of polymer microparticles for controlled drug delivery systems.
Degree: PhD, Biomedical Engineering, 2006, Ohio State University
► We report a novel soft lithography based technique to fabricate non-spherical biodegradable…
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▼ We report a novel soft lithography based technique to fabricate non-spherical biodegradable polymeric microparticles of different sizes and shapes as drug delivery systems. Geometrical control over the shape and size of these microparticles renders them different aerodynamic and fluidic dynamic properties when compared to conventional spherical microparticles and may prove to be beneficial in certain drug delivery strategies, such as pulmonary and intravenous routes. The surface morphology of the particles was studied using a scanning electron microscope and size distribution of the particles was determined using a Coulter counter. The process is reproducible and millions of uniform biodegradable particles of various sizes and shapes with dimensions ranging from 2-30 µm have been fabricated and were collected by a simple vacuum filtration apparatus. In addition, we demonstrated encapsulation of a model drug (FITC), and FITC distributions within the particles were studied by confocal microscopy. Particle size is a critical parameter for several aspects of controlled drug delivery including control of drug-release kinetics, passive targeting to specific cell or tissue types, biodistribution upon administration and available routes of administration. In conclusion, the uniform, biodegradable polymeric microparticles produced have potential to be used in a variety of drug delivery applications and polymer-based microfabrication technology holds promise to produce sophisticated, multi-functional drug delivery devices.
Advisors/Committee Members: Hansford, Derek.
Keywords: Polymer microparticles, drug delivery
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13.
Colon-Jimenez, Lisandra.
Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts.
Degree: MS, Biomedical Engineering, 2010, Ohio State University
► Therapeutic administration of bone marrow derived progenitor cells (BMPC) to infarcted hearts…
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▼ Therapeutic administration of bone marrow derived progenitor cells (BMPC) to infarcted hearts produced promising yet inconsistent results. The goal of this study was to understand the factors limiting cell therapy with BMPC from both, a biochemical and biomechanical perspective. First, we evaluated the effect of oxygen on survival of isolated mouse CD117/c-Kit+ BMPC using the annexin V-propidium iodide assay in flow cytometry. The data showed an intrinsic resistance of these cells to hypoxic conditions, even at longer incubation times. Direct exposure of isolated c-Kit+ BMPC to peroxynitrite (PxN) induced their apoptosis in a time- and concentration- dependent manner, possibly due to a protein modification. One-dimensional western blotting showed a nitrotyrosine-containing band of approximately 83 kDa in cells exposed to the PxN donor, SIN-1, for 20 min and maintained in ambient oxygen. Two-dimensional western blotting revealed a major nitrated band, as well as few satellites. These findings suggest that even though many proteins have tyrosine residues, only few are sensitive to the deleterious modifications induced by PxN. Finally, we studied the effect of size on an ex vivo model of beads perfused within a rat heart in Langendorff mode. The results showed increased retention of large beads (10µm) in the heart after coronary vasodilatation induced by sodium nitroprusside. Nevertheless, increasing elution in successive fractions was observed. In conclusion, ROS-derived nitration is a novel factor potentially limiting the survival of BMPC spontaneously recruited or isolated for administration into ischemic hearts. Geometrical factors, such as relative cell/microvessels size could play a key role in the retention of perfused progenitor cells. These results suggest that nitric oxide could become toxic for stem cells after an infarct when combining with the overly produced ROS. Although it could be beneficial to mediate blood vessel accessibility to circulating progenitor cells through its vasodilatation effect. Altogether, these observations proposed that a ROS-scavenging treatment (i.e. antioxidants) could improve the efficiency of BMPC therapy in patients with myocardial infarction.
Advisors/Committee Members: Moldovan, Nicanor.
Subjects: Biology; Biomedical research; Chemical engineering; Engineering
Keywords: cell therapy; bone marrow stem cells; redox stress; nitrotyrosine
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16.
Dupps, William J. Jr.
Chemo-mechanical modification of the corneal response to photokeratectomy.
Degree: PhD, Biomedical Engineering, 1998, Ohio State University
► Unintended anterior corneal flattening is a poorly understood complication of excimer laser…
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▼ Unintended anterior corneal flattening is a poorly understood complication of excimer laser phototherapeutic keratectomy (PTK) that pervades clinical practice despite efforts to remove a geometrically neutral lenticule of tissue during ablation. This document describes investigations into a model of keratectomy-induced curvature change in which intraoperative thickening of the stroma peripheral to the ablation zone is implicated as a mechanical stimulus for flattening of the central cornea. A paired-control human donor eye study was conducted to assess the efficacy of preoperative topical glutaraldehyde (GTA) treatment as a technique for inhibiting PTK-induced peripheral stromal thickening and, secondarily, for attenuating the acute corneal flattening response.Twenty whole globes acquired in same-donor pairs were individually mounted in a custom holder, inflated to normal intraocular pressure (15 mmHg) and deepithelialized. According to a crosslinking protocol developed in preliminary experiments, one cornea of a given donor pair was immersed in a 15% dextran solution for 40 minutes then transferred to 4% GTA/dextran for an additional 20 minutes; the fellow control was exposed to 15% dextran for 60 minutes. Each eye was subsequently subjected to 1) sham PTK, a same-eye control phase incorporated to account for thinning due to intraoperative dehydration, 2) PTK (5-mm-diameter, 100-um-depth) and 3) a 1-hour hypo-osmotic soak phase designed to assess the anti-swelling activity of stromal crosslinking. A scanning-slit topography system was used to acquire triplicate thickness and curvature measurements before and after each experimental phase.Crosslinking significantly inhibited peripheral stromal thickening during PTK and postoperative hypo-osmotic immersion. In addition, during PTK, crosslinked corneas demonstrated 36% less hyperopic shift relative to paired controls (p = .001). The magnitude of this latter effect was linearly dependent upon the magnitude of crosslink-mediated suppression of the peripheral thickening response to PTK (r = 0.68, p =.03). The results demonstrate that acute hyperopic shifts in a donor model of PTK can be significantly reduced through preoperative application of a collagen crosslinking reagent and therefore support the conclusion that mechanical events in the corneal periphery play an important role in keratectomy-induced central curvature changes. This mechanism of curvature change is not accounted for in current surgical algorithms.
Advisors/Committee Members: Roberts, Cynthia.
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18.
ElDahdah, Hamid Joseph.
DEVELOPMENT OF A HANDHELD INTEGRATED DYNAMIC IMAGING SYSTEM AND REMOTE VESSEL OCCLUDER FOR CANCER DETECTION AND TREATMENT.
Degree: MS, Biomedical Engineering, 2009, Ohio State University
► The first part of the research is dedicated to the diagnosis of…
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▼ The first part of the research is dedicated to the diagnosis of breast cancer with the aid of imaging technologies. The Dynamic Breast Imaging System (DBIS) is an innovative medical device for analyzing the structural and physiologic characteristics of breast tissue and for characterizing/differentiating malignant tumors, benign tumors, and normal breast tissue. This research constructed a handheld probe and corresponding software that simultaneously uses ultrasound and near-infrared light in a dynamic fashion to detect and characterize tissue properties. The combined usage of physiologic and structural data provides a holistic view of the properties of breast tissue and suspicious lesions and aid in image reconstruction. The DBIS probe incorporates pressure sensors to allow the operator to make cyclic compression patterns for breast tissue characterization. Several benchtop tests were conducted to test the system's efficiency, reliability and reproducibility. We are currently planning gathering data through clinical trials at the James Cancer Hospital in Dublin Ohio. The second part of the research focuses on cancer treatment with the development of an innovative occlusion device used in conjunction with ablation processes. It is observed, by controlling the blood flow to a region of interest, one can significantly affect the coagulation lesion size during cancer ablation procedures. We describe the design, development and validation of a remote vessel occlusion device that quantitatively controls vascular perfusion in a repeatable fashion. The occlusion device consists of a flexible cannula containing a shape memory alloy wire with its proximal end tied to a surgical suture and its distal end connected to a driver circuit. The electronic circuit regulates the voltage in the memory alloy wire controlling its amount of reduction in length, tightening the surgical suture. To validate the quantitative control of blood flow, the vessel occluder ligated a vessel simulator that underwent perfusion with dilute porcine blood at five different occlusion levels. The ligation device was then tested for repeatability on a wild type mouse where a cyclic pattern of vessel occlusion and release was performed on the mouse‟s femur artery. The device was further tested on a cancer mouse model that had a cancerous growth on its leg. During ligation of the simulated vessel, a linear correlation between the occluder voltage and the resultant vascular blood flow was observed. For the tests on the wild type mouse and cancer mouse model, corresponding changes in tissue oxygen and hemoglobin concentrations were detected using an oximeter. Future work includes a wider range of occlusion levels to achieve a continuous change in blood flow and better portability.
Advisors/Committee Members: Xu, Ronald.
Subjects: Biomedical research
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20.
Ferrell, Nicholas Jay.
Polymer Microelectromechanical Systems: Fabrication and Applications in Biology and Biological Force Measurements.
Degree: PhD, Biomedical Engineering, 2008, Ohio State University
► Polymer materials are increasingly being utilized in biomedical micro- and nanotechnolgy applications.…
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▼ Polymer materials are increasingly being utilized in biomedical micro- and nanotechnolgy applications. This trend has been driven by a several factors ranging from materials compatibility to cost. The manufacturing techniques used to produce these devices are considerably less mature than their silicon-based counterparts. New manufacturing techniques are needed to address unique processing challenges posed by polymer materials. To this end, we have developed a set of soft lithography based micromolding techniques for fabrication of polymer microstructures and devices from a wide range of materials. Materials include common thermoplastic polymers such as poly(methyl methacrylate) (PMMA) and polystyrene as well as functional materials such as conducting polymers. The processing techniques developed through this work are capable of producing a wide range of structures including continuous microstructured films, isolated polymer microstructures, and suspended structures. The nature of the materials and the non-cleanroom based micromolding processes makes these techniques considerably more cost effective with respect to both materials and processing costs. In addition to developing processing techniques, characterization of the processes as well as the materials is a critical step for implementation of polymers in practical device applications. Process characterization was performed by systematically varying process parameters and evaluating the resulting microstructures using common micro- and nanoscale characterization techniques. Scanning electron microscopy, atomic force microscopy, and optical microscopy were all used to evaluate the resulting polymer structures. Nanoindentation techniques were used to characterize the mechanical properties of the materials. Elastic modulus, hardness, creep, scratch resistance, and yield strength of several polymer MEMS materials were evaluated. Application of these techniques for development of functional devices is ultimately the goal. We have used the processing techniques that we have developed to fabricate and test three polymer MEMS devices for biological applications. The first is a microfabricated membrane system for isolation of individual cells or cell clusters. This device could be utilized in a variety of cell biology applications including single cell experimentation, cell cluster biology, and tissue engineering. The other two devices were developed for measuring low magnitude biological forces. A polymer cantilever force sensor was developed for measuring contractile forces produced by fibroblast cells. This device could be used in cell mechanobiology studies, drug evaluation, and cell-based biosensing. The final device is an adapted polymer cantilever sensor for measuring forces produced by protein aggregates known a forisomes. This unique biomaterial could be utilized as a valve or actuator in microdevices.
Advisors/Committee Members: Hansford, Derek.
Subjects: Engineering
Keywords: microfabrication; MEMS; polymers; biomedical devices
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21.
Flynn, Lisa A.
Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells.
Degree: MS, Biomedical Engineering, 2009, Ohio State University
► Discoidin Domain Receptors (DDRs) are unique members of the Receptor Tyrosine Kinases…
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▼ Discoidin Domain Receptors (DDRs) are unique members of the Receptor Tyrosine Kinases (RTKs) family. Most RTKs are activated by soluble proteins present in bodily fluids, however DDRs are activated by the extracellular matrix (ECM) protein, collagen. Collagen fiber assembly is a tightly controlled process affecting many physiological processes. DDR expression and activation plays a crucial role in collagen assembly, ECM remodeling, cell adhesion and proliferation. Our earlier studies established a unique mechanism of collagen regulation by DDR2 extracellular domain (ECD). This work further investigates how DDR1 ECD and DDR2 ECD affects collagen fibrillogenesis. Mouse osteoblast cell lines stably or transiently over-expressing DDR1 or DDR2 ECD were utilized. Transmission electron microscopy, fluorescence microscopy, and hydroxyproline assays demonstrated that DDR ECD expression reduced the rate and quantity of collagen deposition and significantly altered fiber morphology. Collectively, our studies advanced our understanding of DDRs as powerful regulators of collagen deposition in the ECM.
Advisors/Committee Members: Agarwal, Gunjan.
Subjects: Biomedical research; Cellular biology
Keywords: DDR1; DDR2; collagen fibrillogenesis; DDR extracellular domain
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22.
Gallego-Perez, Daniel.
MICRO/NANOSCALE ENGINEERING OF THE CELL MICROENVIRONMENT.
Degree: PhD, Biomedical Engineering, 2011, Ohio State University
► The cellular microenvironment/niche plays a significant role in the regulation of a…
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▼ The cellular microenvironment/niche plays a significant role in the regulation of a host of physiological and pathophysiological processes. Autonomous signals derived from the intrinsic cell machinery can be inhibited or potentiated by soluble or insoluble factors present in such niche in the form of chemical, structural, and topographical cues. Similarly, specific cell behaviors can be evoked by the same factors even in the absence of intracellular inputs. A normal or aberrant interplay between the cells and their niche could determine for example either the continuation of a regular biological process, or the onset of a disease. Consequently, a better understanding of the mechanisms underlying these cell-microenvironment interactions could help to develop novel therapies for a number of conditions. Micro- and nanoscale technologies have been shown to offer unique capabilities to probe and recapitulate many aspects of the cellular microenvironment. In this thesis, we explored a number of scenarios of clinical and/or biological/biomedical relevance where such technologies could be implemented, with the ultimate goal being the regulation of a specific cell behavior (depending on the application) via micro/nanoscale manipulation of the environment. The first chapters, therefore, discussed the use of conventional materials processing techniques to modify the nano and microstructural properties of a cement material for bone repair/regeneration. Subsequent chapters introduced a set of soft lithography-based techniques that could yield 3D scaffolding structures and/or 1D/2D surface textures that have the potential to better recapitulate the complexity of tissue-specific cellular niches in different applications. Finally, the last chapters illustrated how micro- and nanomanufacturing approaches can be used synergistically to develop systems with a higher degree of complexity, which could be of interest in cell therapy, and drug discovery among other fields.
Advisors/Committee Members: Hansford, Derek.
Subjects: Biomedical Engineering; Biomedical Research; Cellular Biology; Dentistry; Materials Science; Medicine; Nanoscience; Neurobiology; Oncology
Keywords: Biomaterials, Cell Microenvironment, Microtechnology, Nanotechnology, Tissue Engineering
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23.
Ghosh Dastidar, Samanwoy.
Models of EEG data mining and classification in temporal lobe epilepsy: wavelet-chaos-neural network methodology and spiking neural networks.
Degree: PhD, Biomedical Engineering, 2007, Ohio State University
► A multi-paradigm approach integrating three novel computational paradigms: wavelet transforms, chaos theory,…
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▼ A multi-paradigm approach integrating three novel computational paradigms: wavelet transforms, chaos theory, and artificial neural networks is developed for EEG-based epilepsy diagnosis and seizure detection. This research challenges the assumption that the EEG represents the dynamics of the entire brain as a unified system. It is postulated that the sub-bands yield more accurate information about constituent neuronal activities underlying the EEG. Consequently, certain changes in EEGs not evident in the original full-spectrum EEG may be amplified when each sub-band is analyzed separately. A novel wavelet-chaos methodology is presented for analysis of EEGs and delta, theta, alpha, beta, and gamma sub-bands of EEGs for detection of seizure and epilepsy. The methodology is applied to three different groups of EEGs: healthy subjects, epileptic subjects during a seizure-free interval (interictal), and epileptic subjects during a seizure (ictal). Two potential markers of abnormality quantifying the non-linear chaotic EEG dynamics are discovered: the correlation dimension and largest Lyapunov exponent. A novel wavelet-chaos-neural network methodology is developed for EEG classification. Along with the aforementioned two parameters, the standard deviation (quantifying the signal variance) is employed for EEG representation. It was discovered that a particular mixed-band feature space consisting of nine parameters and LMBPNN result in the highest classification accuracy (96.7%). To increase the robustness of classification, a novel principal component analysis-enhanced cosine radial basis function neural network classifier is developed. The rearrangement of the input space along the principal components of the data improves the classification accuracy of the cosine radial basis function neural network employed in the second stage significantly. The new classifier is as accurate as LMBPNN and is twice as robust. Next, biologically realistic artificial neural networks are developed to reach the next milestone in artificial intelligence. First, an efficient spiking neural network (SNN) model is presented using three training algorithms: SpikeProp, QuickProp, and RProp. Three measures of performance are investigated: number of convergence epochs, computational efficiency, and classification accuracy. Next, a new Multi-Spiking Neural Network (MuSpiNN) and supervised learning algorithm (Multi-SpikeProp) are developed. Finally, the models are applied to the epilepsy and seizure detection problems to achieve high classification accuracies.
Advisors/Committee Members: Adeli, Hojjat.
Keywords: Temporal Lobe Epilepsy; Electroencephalogram (EEG); EEG Classification; Epilepsy Diagnosis; Seizure Detection; Wavelet Transform; Chaos Theory; Artificial Neural Networks; Spiking Neural Networks; Principal Component Analysis; Cosine Radial Basis Function
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24.
Giedt, Randy James.
Real-Time Acquisition and Analysis of Endothelial Mitochondrial Superoxide Radical Production and Membrane Potential During In Vitro Ischemia/Reperfusion.
Degree: MS, Biomedical Engineering, 2009, Ohio State University
► The focus of this project was to elucidate the effects of ischemia/reperfusion…
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▼ The focus of this project was to elucidate the effects of ischemia/reperfusion on mitochondrial superoxide production by cultured endothelial cells in a parallel plate flow chamber in real time. To accomplish this, we used the mitochondria-targeted superoxide-specific fluorescent probe mitoSOX to determine parameters for its most effective use in a system composed of a parallel-plate flow chamber with cultured endothelial cells, a Nikon epifluorescence microscope, and digital image processing software. Based on the literature, the probe’s mitochondrial specificity is linked with the cell mitochondrial membrane potential. This made it necessary to study the effects of ischemia/reperfusion on mitochondrial membrane potential because of the possibility for mitoSOX to leak out of the mitochondria upon loss of mitochondrial membrane potential. The fluorescent probe rhodamine 123 was used in a similar manner as mitoSOX to accomplish this goal. The combination of the novel flow system and mitoSOX enabled us to obtain data comparable to that of a confocal microscope, as verified by the use of a variety of positive controls (both static endpoint images and real time analysis). Experiments using mitoSOX during ischemia/reperfusion showed a higher rate of mitochondrial superoxide production than that of shear alone, while the same experiments using rhodamine 123 showed a loss of mitochondrial membrane potential during ischemia and a partial recovery upon reperfusion. These studies may help us understand the mechanisms of injury on the mitochondria of coronary artery endothelial cells following cardiac ischemia/reperfusion.
Advisors/Committee Members: Alevriadou, Barbara R.
Subjects: Cellular biology; Mechanical engineering; Molecular biology
Keywords: Superoxide; MitoSOX; endothelial cells; mitochondria; membrane potential; ROS; Reactive Oxygen Species; Free Radicals; Ischemia; Ischemia/Reperfusion Injury
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25.
Giedt, Randy James.
Mitochondrial Network Dynamics in Vascular Endothelial Cells Exposed to Mechanochemical Stimuli: Experimental and Mathematical Analysis.
Degree: PhD, Biomedical Engineering, 2012, Ohio State University
► This work was conducted in order to assess the role that the…
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▼ This work was conducted in order to assess the role that the mitochondrial network plays in cardiovascular disease. More specifically, we first conducted studies to determine which bioenergetic factors control changes in the mitochondrial network by exposing cultured endothelial cells to specific chemical treatments. Following this work, we used a parallel plate flow chamber and media recirculation system to expose cultured endothelial cells to simulated ischemia (I)/ reperfusion (RP) injury in order to determine if changes in the mitochondrial network occur upon I/RP and delineate the molecular mechanisms that govern them. The mitochondrial network is dynamic with conformations that vary between a tubular continuum and fragmented state. The equilibrium between mitochondrial fusion/fission, as well as the organelle motility, determine network morphology and ultimately mitochondrial/cell function. Network morphology has been linked with the energy state in different cell types. As stated, in the first part of this study, we examined how bioenergetic factors affect mitochondrial dynamics/motility in cultured vascular endothelial cells (ECs). ECs were transduced with mitochondria-targeted green fluorescent protein (mito-GFP) and exposed to inhibitors of oxidative phosphorylation (OXPHOS) or ATP synthesis. Time-lapse fluorescence videos were acquired and a mathematical program that calculates size and speed of each mitochondrial object at each time frame was developed. Our data showed that inner mitochondrial membrane potential, ATP produced by glycolysis, and, to a lesser degree, ATP produced by mitochondria are critical for maintaining the mitochondrial network, and different metabolic stresses induce distinct morphological patterns (e.g., mitochondrial depolarization is necessary for “donut” formation). Mitochondrial movement, characterized by Brownian diffusion with occasional bursts in displacement magnitude, was inhibited under the same conditions that resulted in increased fission. Hence, imaging/mathematical analysis shed light on the relationship between bioenergetics and mitochondrial network morphology; the latter may determine EC survival under metabolic stress. I/RP-induced endothelial cell (EC) injury is thought to be due to mitochondrial reactive oxygen species (mtROS) production. MtROS have been implicated in mitochondrial fission. In the 2nd section of this study, we determined whether cultured EC exposure to simulated I/RP causes morphological changes in the mitochondrial network and the mechanisms behind those changes. Because shear stress results in nitric oxide (NO)-mediated endothelial mtROS generation, we simulated I/RP as hypoxia (H) followed by oxygenated flow over the ECs (shear stress of 10dyn/cm2). By exposing ECs to shear stress, H, H/reoxygenation (RO), or simulated I/RP and employing MitoTracker staining, we assessed the differential effects of changes in mechanical forces and/or Oxygen levels on the mitochondrial network. Static or sheared ECs maintained their mitochondrial network. H- or H/RO-exposed ECs underwent changes, but mitochondrial fission was significantly less compared to that in ECs exposed to I/RP. I/RP-induced fission was partially inhibited by antioxidants, a NO synthase inhibitor, or an inhibitor of the fission protein dynamin-related protein 1 (Drp1) and was accompanied by Drp1 oligomerization and phosphorylation (Ser616). Hence, shear-induced NO, ROS (including mtROS), and Drp1 activation are responsible for mitochondrial fission in I/RP-exposed ECs, and excessive fission may be an underlying cause of EC dysfunction in postischemic hearts.
Advisors/Committee Members: Alevriadou, B. Rita.
Subjects: Biology; Biomedical Engineering; Biomedical Research; Biophysics; Cellular Biology; Computer Science; Engineering; Mathematics; Mechanical Engineering
Keywords: endothelial cells; mitochondria; reactive oxygen species; ischemia; ischemia/reperfusion; nitric oxide; mitochondrial fusion/fission
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26.
Giri, Shivraman.
Cardiovascular Magnetic Resonance Techniques for Myocardial Tissue Characterization in Coronary Artery Disease.
Degree: PhD, Biomedical Engineering, 2012, Ohio State University
► Accurate diagnosis of coronary artery disease (CAD), a life-threatening condition when in…
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▼ Accurate diagnosis of coronary artery disease (CAD), a life-threatening condition when in acute stage, is a clinical challenge, especially in an emergency setting. Current strategies for the initial triage of chest-pain patients fall short of providing enough diagnostic accuracy, resulting in unnecessary hospitalization of low-risk patients or early discharge of high-risk patients; the former increases societal health-care burden and exposes patients to the risk of invasive procedures and ionizing radiations, whereas the latter leads avoidable mortalities. This research was undertaken with the objective of equipping health-care providers with magnetic resonance imaging (MRI) diagnostic techniques for improved assessment of CAD patients. MRI has many advantages over other techniques: it is non-invasive, involves no ionizing radiations, provides high spatial resolution, is capable of probing multiple biomarkers, can provide information at all levels – molecular, cellular, tissue and organ. Of these, tissue characterization is a unique forte of MRI, and has been exploited in this work. To address the clinical need of finding improved MRI techniques, the pathophysiology of CAD was first investigated to identify the early biomarkers of this disease, with an emphasis on those that signify reversible injury to the heart. Two such biomarkers – myocardial edema and perfusion – were studied in greater detail. MR physics was then reviewed with a view to designing an optimal strategy for characterizing these tissue changes. Finally, engineering solutions, in the form of pulse sequences and post processing strategies, were provided to enable the translation of these techniques from “bench to bedside”. The solution provided for edema characterization is a robust quantitative T2 mapping pulse sequence. Multiple T2-quantification approaches were evaluated to propose an optimal strategy that was shown to address many of the problems that have precluded the use of qualitative T2-weighted approaches for myocardial edema imaging in routine clinical scans. The optimal T2 mapping strategy was then implemented on Siemens 1.5T systems, incorporating novel automatic motion compensation technique into the work-flow. Subsequently, the diagnostic performance of this technique was evaluated in single-center clinical trials for two cardiovascular pathologies: acute myocardial infarction and acute inflammatory diseases. Myocardial perfusion assessment using MRI has been around since 1991; despite advancements in scanner hardware, novel pulse sequences, and reconstruction strategies, several limitations continue to exist. Using the same basic pulse sequence – saturation recovery preparation followed by a fast readout module, most of the contemporary research has focused on advanced acceleration and reconstruction strategies. The solution proposed in this work uses an alternative approach of imaging in steady-state, which circumvents many of the suspected sources of limitations in the current techniques. This pulse sequence can be combined with any of the advanced acceleration technique and could potentially accomplish whole-heart perfusion imaging. Initial experience with this technique is presented and suggestions for its further improvement are provided.
Advisors/Committee Members: Simonetti, Orlando P.
Subjects: Biomedical Engineering; Biomedical Research
Keywords: mri; cardiovascular; coronary artery disease
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28.
Glass, Dianne Henry.
CHARACTERIZATION OF THE BIOMECHANICAL PROPERTIES OF THE IN VIVO HUMAN CORNEA.
Degree: PhD, Biomedical Engineering, 2008, Ohio State University
► The goal of the research is to investigate corneal hysteresis as measured…
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▼ The goal of the research is to investigate corneal hysteresis as measured by the Reichert Ocular Response Analyzer (ORA) and to develop new methods for evaluating the biomechanical properties of the human cornea through the analysis of its deformation in response to an air pulse from the ORA. A mathematical model was developed to simulate the viscoelastic behavior of the cornea during an ORA measurement. The model was validated by comparing the strain behavior of the model to that of a corneal phantom using high speed photography. The model was used to investigate the effects of changes to elasticity or viscosity on hysteresis. High speed photography was used to evaluate and compare the size and symmetry of the corneal deformations between normal corneas and those with keratoconus. The model and high speed photography were used to measure the viscosity and elasticity of the in vivo human. The model utilizes the values for the air pressure applied to the cornea by the ORA, the deformation recorded with the high speed photography to calculate viscosity and elasticity. The high speed photography revealed that the deformation area of keratoconic corneas is smaller than normals and the area correlates with features of the ORA signal. The results for the elasticity and viscosity of normal and glaucomatous corneas were compared, and it was found that the elasticity of glaucomatous corneas is higher than normal corneas. The ability to evaluate in vivo biomechanical properties of the human cornea may useful in differentiating disease states and evaluating response to surgical interventions.
Advisors/Committee Members: Roberts, Cynthia J.
Subjects: Accounting; Biomedical research; Engineering; Mechanics; Ophthalmology
Keywords: cornea, biomechanics, elasticity, viscosity, viscoelasticity, hysteresis, keratoconus, glaucoma
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29.
Grodecki, Joseph.
Behavior of Glioblastoma Cells in Co Culture with Rat Astrocytes on an Electrospun Fiber Scaffold.
Degree: MS, Biomedical Engineering, 2012, Ohio State University
► Gliomas are the most common brain tumor in adults, occurring in more…
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▼ Gliomas are the most common brain tumor in adults, occurring in more than 50% of brain tumor cases. Astrocytomas, or tumors that arise from the astrocytes of the brain, account for 60-70% glioma cases.1 The most common form of glioma is the grade IV astrocytoma known as glioblastoma multiforme.2 The interactions between glioblastoma cells and normal astrocytes have not been thoroughly explored in a three dimensional environment in vitro. This research investigated the co culture of human glioblastoma cells and rat astrocytes in different ratios on electrospun polycaprolactone (PCL) fibers as well as the culture of human glioblastoma cells and rat astrocytes individually on PCL fibers. In particular, the migration of glioblastma cells and GFAP expression of rat astrocytes were measured in both co culture conditions and individual cultures of the cell of interest. The reactivity of astrocytes and the migration of glioblastoma cells was also investigated in the presence of individual factors thought to be affecting behavior of these cells in co culture. The results were then compared in an attempt to identify cell behavioral differences between different conditions. Glioblastoma migration was increased when cells were co cultured with astrocytes and cultured in media conditioned with rat astrocyte released soluble factors. GFAP expression was upregulated in rat astrocytes cultured with glioblastoma cells versus rat astrocytes cultured alone.
Advisors/Committee Members: Winter, Jessica.
Subjects: Biomedical Engineering
Keywords: Glioblastoma Astrocyte Interactions Co Culture Electrospun Fibers
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30.
Grodecki, Joseph.
Behavior of Glioblastoma Cells in Co Culture with Rat Astrocytes on an Electrospun Fiber Scaffold.
Degree: MS, Biomedical Engineering, 2012, Ohio State University
► Gliomas are the most common brain tumor in adults, occurring in more…
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▼ Gliomas are the most common brain tumor in adults, occurring in more than 50% of brain tumor cases. Astrocytomas, or tumors that arise from the astrocytes of the brain, account for 60-70% glioma cases.1 The most common form of glioma is the grade IV astrocytoma known as glioblastoma multiforme.2 The interactions between glioblastoma cells and normal astrocytes have not been thoroughly explored in a three dimensional environment in vitro. This research investigated the co culture of human glioblastoma cells and rat astrocytes in different ratios on electrospun polycaprolactone (PCL) fibers as well as the culture of human glioblastoma cells and rat astrocytes individually on PCL fibers. In particular, the migration of glioblastma cells and GFAP expression of rat astrocytes were measured in both co culture conditions and individual cultures of the cell of interest. The reactivity of astrocytes and the migration of glioblastoma cells was also investigated in the presence of individual factors thought to be affecting behavior of these cells in co culture. The results were then compared in an attempt to identify cell behavioral differences between different conditions. Glioblastoma migration was increased when cells were co cultured with astrocytes and cultured in media conditioned with rat astrocyte released soluble factors. GFAP expression was upregulated in rat astrocytes cultured with glioblastoma cells versus rat astrocytes cultured alone.
Advisors/Committee Members: Winter, Jessica.
Subjects: Biomedical Engineering; Biomedical Research
Keywords: Glioblastoma, Astrocyte, Co Culture, Electrospun Fibers, Migration
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