Organizational Unit:
Wallace H. Coulter Department of Biomedical Engineering

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Publication Search Results

Now showing 1 - 10 of 519
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    Development of ultrasound and photoacoustic imaging tools for tracking of cells and particles
    (Georgia Institute of Technology, 2019-12-16) Kubelick, Kelsey P.
    Development of novel therapies relies heavily on histology to evaluate outcomes. While histology provides detailed information at the molecular level, drawbacks include highly invasive, destructive sample preparation. To this end, clinical translation of novel therapies would be expedited by further developing minimally invasive, longitudinal imaging methods to inform therapy design or provide clinical feedback. Combined ultrasound (US) and photoacoustic (PA) imaging augmented with contrast agents is an excellent option to address this need. This research describes development of a US/PA imaging toolbox, consisting of contrast agents, imaging protocols, imaging hardware, and detection algorithms, that can be tailored for a variety of applications where longitudinal, in vivo imaging of specific cells or particles is desired. To demonstrate versatility, these US/PA imaging tools were developed and combined in different ways for implementation in three distinct applications: 1) stem cell monitoring in ophthalmology to aid development of glaucoma therapies; 2) intra- and post-operative monitoring to guide stem cell therapies of the spinal cord; and 3) monitoring particle trafficking to the lymph node to inform vaccine design. Although the applications investigated here were extremely different, common themes were identified, highlighting broad relevance of the US/PA imaging toolbox and common opportunities for later development. Overall, the tools developed here lay the foundation for design of custom US/PA imaging platforms in the future.
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    The Phenotypic Response of Dendritic Cells to Gold Nanoparticles Treatments
    (Georgia Institute of Technology, 2019-12) Dasgupta, Ayan
    Immunotherapy research has been increasingly investigating the potential of gold nanoparticles (AuNPs). AuNPs pose new benefits in the medical field ranging from diagnostics to diseases treatment. AuNPs’ ability to infiltrate tissue and target immune cells makes their potential highly useful for new proposed personalized immunotherapies[1] regarding antigen specific targeting delivery, tracking capabilities in vivo [2][3], and more effective and direct vaccines [8]. AuNPs act as an adjuvant with the ability to elicit immuno-suppressive or immuno-activated responses depending on the treatment and characterization of the AuNPs. A promising application of AuNPs is their ability to interact with dendritic cells (DCs). DCs are antigen presenting cells (APCs) and play an integral part in both innate and adaptive immune responses. They work by internalizing and presenting antigens on their surface to other immune cells initiating an immunomodulatory response. In previous research, it has been shown that AuNPs engineered with surface molecules can the initiate maturation of immature DCs (iDCs). Depending on the surface molecules, AuNPs can mature iDCs to become either activated or tolerogenic DC phenotypes[1]. These matured DC phenotypes use the AuNP’s surface molecules to then elicit an immune response by presenting the surface molecules to other immune cells in addition to secreting chemokines and cytokines to enhance the immune response. Though AuNPs’ influence on the maturation of iDCs has been increasingly studied, it is still not well understood which is critical in order to develop effective personalized immunotherapies. In this study, the relationship between DC phenotypes and AuNP properties is analyzed in order to optimize the methods used to elicit specific immune responses. iDCs will be cultured and treated with AuNPs with various surface modifications which will then be analyzed to determine the phenotypic character of the cultured DCs. The cultured DCs are analyzed using high-throughput screening and flow cytometry to determine the surface molecules that have developed from the AuNP treatment which will determine which phenotype of the matured iDCs. This analysis will establish a relationship between various AuNP treatments and the resulting phenotypic development of DCs. This research will work towards standardizing maturation methods of DCs in vivo in order to control a patient’s immune system and its responses to fight off diseases and arm immune cells.
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    Pulsatile Flow System for Surgical Robotics
    (Georgia Institute of Technology, 2019-12) Verma, Ankita
    Surgical robotics is an evolving field where robotic medical devices are utilized to perform surgery either on or within the body. In order to mitigate errors that may occur during surgery due to the medical devices being used, testing environments are created for better development of the device and for clinical training. A Pulsatile Flow System (PFS) is a machine that recreates the physiological conditions of flow rate and pressure as the heart pumps blood, and can be created using materials such as pipes and motors. The research at hand developed a PFS and specifically focused on the electrical components of the system, using a motor, a motor controller, a flow sensor, and a circuit board. By creating code that is able to control the system and the speed at which the PFS functions, the system was able to pump water at 40 beats per minute through the circuit. Moving forward, the PFS can be improved to become an even more accurate model by including changes such as substituting the water in the system with a liquid of a similar viscosity to blood. The development of a machine like this is crucial in order to provide a cost effective system capable of imitating the human body in order to properly test surgical robots that travel through arteries in the body. Using an external testing environment will ensure that the devices created in the laboratory are properly developed before they are used in surgery, ensuring that the patient’s life is kept out of harm’s way.
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    Investigation of the Cytokine and Chemokine Response of Dendritic Cells Following Gold Nanoparticle Treatments and Variations in Hydrogels
    (Georgia Institute of Technology, 2019-12) Arya, Priya
    Immunotherapies have significant potential for implementation towards personalized medicine through avenues such as vaccine, gene, and cancer applications. Dendritic cells are a major contributor in the immune system, functioning as antigen-presenting cells that aid in orchestrating the immune response towards pathogenic activators. Manipulation of these cells can allow for the optimization of immune responses, which can be achieved through tissue engineering and modulation via gold nanoparticles. This study seeks to provide a basis for elucidating the secretory responses of immature dendritic cells as they progress through maturation following treatment with modified gold nanoparticles. Additionally, findings are presented on the manipulation of dendritic cells with a variety of treatments such as PEGylation and thiolation to understand resulting effects on IL-10 expression. Biomaterial-based matrices are additionally investigated for their roles in dendritic cell viability and functionality – results of variation in weight percentage of hydrogels, used for dendritic cell encapsulation, will be shown. With some notable exceptions, such as IL-4, the majority of cytokine and chemokine expressions in experimental cell groups compared to baseline immature dendritic cell expression levels decreased. Future studies should continue to characterize and solidify this response, both with regard to modulation in hydrogels and gold nanoparticles. These studies can aid in paving the way for individualized treatment for autoimmune disorders.
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    Efficacy of an International Student Orientation Course
    (Georgia Institute of Technology, 2019-12) Bell, Mark Reeves
    Culture shock is a prominent phenomenon for international students when beginning college. The term ‘culture shock’ is defined as a negative emotional reaction caused by the overwhelming and confusing flood of unfamiliar behavior in a new culture. Culture shock induces stress through frustration with culture norms, and experiencing culture shock causes many struggles including language difficulties, homesickness, and social isolation. Culture shock is salient to undergrads because they are young and seemingly on their own immediately after they move. Moreover, American colleges and universities have dramatically increased their numbers of international students, especially students from culturally different eastern countries. These particular students have shown noticeable levels of culture shock during their first semester of college. This study was designed to determine the efficacy of a three-week international student orientation course for first-year international students. The first session introduced students to possible differences they might experience in the American culture and the social norms put in place. The second session introduced students to the wide variety of resources on and off campus. This was an informational session to help compensate for the shortened FASET orientation that international students receive. The third session introduced students to different role-playing scenarios, including negotiating a friendship, working in groups, and meeting a professor for office hours. Measurements for the efficacy included mental health surveys over seven weeks, pre- and post-course questions on culture shock, and course evaluations. Due to low participation, the quantitative analysis returned statistically non-significant results. Regardless, the study showed promise in future research.
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    Discovering potential combinational treatments of Amyotrophic Lateral Sclerosis (ALS) using a computational model of G93A mouse.
    (Georgia Institute of Technology, 2019-12) Lee, Albert Jong
    Instabilities in the regulatory mechanisms utilized by the superoxide dismutase 1 glycine 93 to alanine (SOD1 G93A) transgenic mouse to compensate for changes to the system have been postulated to play a considerable role in Amyotrophic Lateral Sclerosis (ALS) disease progression. However, there is currently no concrete evidence of such regulatory dysfunctions in the SOD1 G93A mouse. In order to study the complexity of ALS, a computational model of wild type (WT) mouse physiological regulation was developed using a combination of dynamic meta-analysis (DMA) and global optimization. Such model was shown to be able to predict the time dynamics of WT physiological functions. The method presented in this study will be used to construct a G93A model and can be further applied to other multifunctional diseases.
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    Immuno-suppressive hydrogels for stem cell therapy after traumatic brain injury
    (Georgia Institute of Technology, 2019-11-20) Alvarado-Velez, Melissa
    During a traumatic brain injury (TBI) an external force disrupts the brain tissue and the proper functioning of neuronal pathways. This initial insult activates multiple cellular mechanisms that further propagate the tissue damage causing a secondary injury that exacerbates neurological deficits. This phase, known as the secondary injury, opens a therapeutic window in which neuroprotective treatments that successfully contain the propagation of the initial damage could significantly reduce neurological deficits associated with TBI. Mesenchymal stem cell transplantation (MSC) after TBI has been found to ameliorate neurological deficits due to the ability of the stem cells to modulate inflammation and immune cells and to increase the expression of neurotrophic factors that promote the survival of the neuronal tissue surrounding the injury site. However, the active rejection of the transplanted MSC by the host immune system could strongly diminish the stem cell's survival and therapeutic effect. In this thesis, we used immunosuppressive hydrogels, specifically designed to induce the apoptosis of cytotoxic CD8+ T cells, to enhance the survival of transplanted MSC in the injured brain. We demonstrated that creating localized immunosuppression near the MSC transplantation site resulted in a higher presence of MSC near the injury site. We also demonstrate that enhancing MSC survival by using immunosuppressive hydrogels increased the protein expression of the neurotrophic factors, which could lead to reduced neuronal damage. Therefore, the development of immune-suppressive hydrogels for stem cell transplantation could be a successful approach to enhance stem cell therapy after TBI.
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    Quasi-periodic patterns of brain intrinsic activity coordinate the functional connections in humans
    (Georgia Institute of Technology, 2019-11-12) Yousefi, Behnaz
    The brain is a complex self-organizing biophysical system and intrinsically very active. How such intrinsic activity organizes the brain in humans is widely being studied during resting-state using functional magnetic resonance imaging (rsfMRI) and the functional connectivity (FC) metric. FC, calculated as the Pearson correlation between rsfMRI timeseries from different brain areas, indicates coherent activity on average over time, and can reflect some spatial aspects of the brain’s intrinsic organization. For example, based on the FC profile of each area, the cerebral cortex can be parcellated into a few resting-state networks (RSNs) or exhibit a few functional connectivity gradients (FCGs). Brain is a complex system and exhibits varied dynamic spatiotemporal regimes of coherent activity, which are still poorly understood. A subset of such regimes should be giving rise to FC, yet they might entail significantly insightful aspects about the brain’s self-organizing processes, which cannot be captured by FC. Among such dynamic regimes is the quasi-periodic pattern (QPP), obtained by identifying and averaging similar ~20s-long segments of rsfMRI timeseries. QPP involves a cycle of activation and deactivation of different areas with different timings, such that the overall activity within QPP resembles RSNs and FCGs, suggesting QPP might be contributing to FC. To robustly detect multiple QPPs, method improvements were implemented and three primary QPPs were thoroughly characterized. Within these QPPs activity propagates along the functional gradients at the cerebral cortex and most subcortical regions, in a well-coordinated way, because of the consistencies and synchronies across all brain regions which reasonably accord with the consensus on the structural connections. Nuanced timing differences between regions and the closed flow of activity throughout the brain suggest drivers for these patterns. When three QPPs are removed from rsfMRI timeseries, FC within and particularly between RSNs remarkably reduces, illustrating their dominant contribution. Together, our results suggest a few recurring spatiotemporal patterns of intrinsic activity might be dominantly coordinating the functional connections across the whole brain and serving self-organization. These intrinsic patterns possibly interact with the external tasks, affecting performance, or might provide more sensitive biomarkers in certain disorders and diseases.
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    Computational Modeling of Left Ventricle-Valve Dynamics using a Fluid-Structure Interaction Framework
    (Georgia Institute of Technology, 2019-11-12) Caballero, Andres D.
    The left heart (LH) is a key player of the cardiovascular system. Diseases of and associated with the left ventricle (LV)-valve complex account for a large share of cardiovascular disease-related deaths. As accurate and detailed interrogation of cardiac function has been actively pursued clinically in recent years, computational modeling has emerged as a viable approach to study the LH dynamics in healthy and diseased states. Yet, most of the previous computational investigations have either solved the fluid or structural physics alone, have been limited to idealized or 2D geometries, have adopted linear elastic material models, have focused on a short time frame of the cardiac cycle, or have not incorporated all LH structures. Proper LV-valve dynamics require a balanced interplay between the LV, the left atrium, the aortic valve (AV), the mitral valve (MV) and the blood flow. Thus, blood-leaflet interaction, leaflet coaptation, and flow dynamics into, within and outward of the LV are all critical parameters to investigate, an area where fluid-structure interaction (FSI) computational modeling is required. The main objective of this work is to model the FSI between the blood flow, the heart valves and the cardiac wall during the entire cardiac cycle in order to improve our understanding of the biomechanics of the LH complex under baseline, diseased and repaired states. First, a novel FSI framework for modeling the 3D LV-valve dynamics will be developed and validated. Aim 1 will involve the creation of physiologic and pathological LH models that incorporate imaged-based cardiac wall motion, anatomically accurate valve geometries, anisotropic nonlinear hyperelastic constitutive models, and human cardiac tissue material properties. Next, these holistic LH models will be used to better understand the biomechanical challenges facing transcatheter valve technologies that cannot be fully evaluated by finite element (FE) or computational fluid dynamics (CFD) models, or by in vitro studies or medical imaging alone. Thus, Aim 2 will investigate the LH dynamics under various transcatheter MV repair (TMVR) and transcatheter AV replacement (TAVR) procedures. The findings from this study may unfold new perspectives for an improved understanding of cardiovascular pathophysiology, device-host biomechanical interaction, inform treatment strategies, support better device design, and ultimately support improved clinical outcomes.
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    Aqueous Two-Phase System Micro-Assays Augmented by Automated Image Analysis
    (Georgia Institute of Technology, 2019-11-12) Yamanishi, Cameron Damion
    Aqueous two-phase systems (ATPS) are a quirk of thermodynamics, wherein two immiscible solutions separate into stable liquid phases, containing primarily water. Conveniently, some biomolecules partition favorably into one phase or the other. Recently, these properties have been used for many applications, including micropatterning, purification, target concentration, and reagent segregation. In this work, we examined a previously under-appreciated property of ATPSs – the spontaneous generation of circulating fluid flow with ATPS micro-droplets. First, we developed and validated a novel imaging modality, stigmatic microscopy, to perform the first 3D measurements of ATPS micro-droplet self-driven circulation. This technique borrows concepts from super-resolution microscopy to identify the 3D positions of fluorescent microbeads from individual image frames. Specifically, the use of a toroidal lens shifts the x-focal plane apart from the y-focal plane, enabling determination of z-position from the point-spread function of the image. We designed the microscope using optical modeling to determine usable lens strengths and distances. After constructing the microscope, we developed software to determine 3D positions of fluorescent micro-beads and link the positions from time frame to time frame to track flow. Second, we enhanced the performance of an ATPS multiplex immunoassay. In previous work from our lab, antibody pairs are spotted in ATPS micro-droplets to co-localize them, preventing crosstalk between incorrect antibody pairs. We advanced this assay from a manually spotted method to a pre-dried format, wherein one phase of the ATPS is rehydrated by the other. We demonstrated that antibody segregation is maintained throughout the rehydration process. With further consideration of self-driven flow, we reduced assay incubation time drastically, first in a two-wash format and subsequently in a one-wash format. Further examination of the competing ATPS parameters identified an optimal medium between viscosity, partition behavior, and convective flow. Third, we extended another ATPS bioassay from our lab – collagen microgel contraction to facilitate research on pulmonary fibrosis, a deadly disease with no effective treatments. The collagen gel contraction assay is a helpful measurement of the wound healing activity of fibroblasts. However, current formats use large numbers of cells, restricting their use with primary lung fibroblast cells, which have limited growth capacity. To address the issue, our lab previously used ATPS to generate microscale bioprinted collagen gels and demonstrated proof-of-concept with cell lines. However, the behavior of primary cells proved more difficult to study, due to small effect sizes. To overcome this obstacle, we incorporated higher throughput and use continuous imaging (as opposed to end point assays). This yielded a markedly more reliable assay, which we used to observe the effects of current and potential therapeutics. Notably, we identify differences between normal and diseased fibroblasts in their contraction kinetics at moderate doses of anti-fibrotic drugs.