Browsing by Subject "Sickle cell disease"

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    Functional Multimodal Imaging Of Sickle Cell Disease Patients To Understand How Chronic Pain Affects Neural Dynamics Of Patients
    (2018-05) Case, Michelle
    Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Pain is the most common reason for hospitalization in SCD patients and is often experienced on a daily basis. Treatment of pain in SCD patients remains challenging due to a poor understanding of the mechanisms, especially in the brain. Therefore, an in-depth analysis of how chronic pain affects SCD patients is needed to provide a foundation for future research and improved treatment options. The goal of this research is to use multimodal non-invasive imaging techniques to better understand the neural dynamics of SCD patients and how these differ from a normal healthy brain. Utilizing both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allowed spatiotemporal analysis of resting state neural behavior of SCD patients and healthy controls. This work includes (1) a simultaneous EEG-fMRI study to determine biomarkers of sickle pain and how resting state networks are altered in patients, (2) an EEG analysis utilizing EEG power and electrical source imaging analysis to classify between patients and controls, and (3) a graph theory study using both EEG and fMRI to understand the global impact of sickle pain on the brain and to utilize imaging to detect differences not only between patients and controls, but also between patients with more severe chronic pain and less severe chronic pain. This study showed how imaging parameters found from non-invasive imaging modalities are related to chronic pain in SCD patients and will be used in future work to guide new treatment options and validate their effectiveness on improving brain dynamics.
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    Multiscale and Multiphysics of Blood Flow and Arterial Mechanics Growth and Remodeling
    (2024-01) Schmidt Bazzi, Marisa
    The circulatory system, resembling a complex network of pipes (blood vessels) and a ceaseless pumping system (heart), orchestrates the delivery of oxygen and nutrients to every cell and tissue in the human body. Unlike conventional engineering pipes, vascular tissue exhibits the remarkable ability to adapt its physical and mechanical properties in response to its environment, a phenomenon known as growth and remodeling (G&R). This process aims to maintain a balanced stress level, termed homeostatic stress.In healthy arteries, maintaining mechanical equilibrium involves a clever negative feedback loop that restores the system to its preferred state after any disturbances. However, when this delicate balance is disrupted, it can lead to a phenomenon called pathological G&R, characterized by a positive feedback loop. Aortic and intracranial aneurysms are prominent examples of this disrupted G&R. Characterized by the enlargement of vessels, aneurysms pose significant health risks, contributing to numerous annual fatalities. Moreover, blood disorders such as sickle cell disease can disrupt mechanical equilibrium by altering blood flow dynamics and creating localized hypoxia, especially in small arteries, such as the one found in our brain. Therefore, recognizing the connection between blood disorders and tissue-related diseases underscores the importance of exploring the interplay between fluid dynamics and tissue mechanics. This thesis investigates the interplay between computational fluid dynamics, mathematical modeling, and finite element analysis in the context of cardiovascular diseases. It primarily focuses on ascending thoracic and intracranial aneurysms related to sickle cell disease. We aim to enhance our understanding of the intricate mechanisms underlying vascular diseases. This heightened insight will be central in developing more holistic diagnostic and therapeutic approaches to effectively lessen their significant impact on individuals' health.
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    Regulation and Effects of Heme-Oxygenase-1 Expression in Chronic Inflammation.
    (2010-06) Beckman, Joan Denise
    Heme oxygenase-1 (HO-1) enzyme plays critical role in metabolizing the excess heme generated during hemolysis in pathological conditions, such as sickle cell disease. We and others have previously demonstrated that during chronic intravascular hemolysis the expression of HO-1 protein is not sufficient to reduce the oxidative burden of free heme in the vasculature, leading to oxidative stress and vascular inflammation. This proposal examined two areas critical to the understanding of HO-1 expression and function during inflammation: the role of post-transcriptional regulation in control of protein expression and the importance of its by-product carbon monoxide (CO) in mediating anti-inflammatory, anti-apoptotic effects. The research utilized a murine sickle model which has perturbations of heme catabolism leading to oxidative stress and inflammation. Studies in this model will test whether HO-1, or its by-products, can therapeutically alter the natural history of sickle cell disease. In addition, cell culture models in which heme levels are controlled were used to explore microRNA regulation of heme oxygenase-1 (HO-1) expression. Combined these experimental endeavors aim to identify new aspects of HO-1 research.