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Chest Computed Tomography And Magnetic Resonance Imaging Texture Measurements Of Chronic Obstructive Pulmonary Disease, Maksym Sharma

Electronic Thesis and Dissertation Repository

Pulmonary imaging using computed tomography (CT) and magnetic resonance imaging (MRI) provide a method to measure airway and parenchymal pathologic information that cannot be provided using spirometry. Currently, it remains difficult to predict which chronic obstructive pulmonary disease (COPD) patients will worsen using spirometry, which although safe and inexpensive, does not provide small airway information where COPD is believed to initiate. Quantitative CT and MRI measurements provide regional structure and function information but are not included in mortality risk assessments, prognosis, or COPD staging. Therefore, my overarching hypothesis is that CT and MRI ventilation texture measurements combined with machine learning …

Structure And Function Of Long-Covid Evaluated Using Pulmonary Imaging, Harkiran Kaur Kooner

Electronic Thesis and Dissertation Repository

The COVID-19 pandemic has resulted in millions of global respiratory infections, ranging in severity from asymptomatic to fatal. One of the many consequences of the pandemic is the emergence of long-COVID, which is an umbrella term used to describe the long-term sequelae and poor quality-of-life following recovery from acute COVID-19 infection. However, the pathophysiology and mechanisms responsible for the heterogenous manifestation of long-COVID remain poorly understood. Hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) provides a non-invasive and radiation-free method to regionally visualize and quantify inhaled gas distribution and ventilation in vivo. A strong foundation for the use of pulmonary …

Validation Of A Virtual Auditory Space, And Its Use To Investigate How Pitch And Spatial Cues Contribute To Perceptual Segregation Of Auditory Streams, Nima Zargarnezhad

Electronic Thesis and Dissertation Repository

The human auditory system can decompose complex sound mixtures into distinct perceptual auditory objects through a process (or processes) known as Auditory Scene Analysis. Pitch and spatial cues are among the sound attributes known to influence sequential streaming (Plack 2018). In this project, the fidelity of a virtual acoustic space (the Audio Dome) in reproducing precisely located sound sources with a 9^th-order ambisonics algorithm was validated. The estimated horizontal Minimum Audible Angles aligned with previously reported values (Mills 1958) homogeneously across the space, and a robust low-frequency presentation was identified. Then, the Audio Dome was utilized to test …

Lbnp Reduces Cerebral Perfusion But Does Not Impact Executive Function, James Van Riesen

Electronic Thesis and Dissertation Repository

A growing body of literature has demonstrated that a single bout of aerobic exercise and/or hypercapnic manipulations increase cerebral blood flow (CBF) and are linked to a transient (i.e.,min) post-intervention executive function (EF) benefit. However, there are no direct studies examining whether a transient decrease in CBF elicits a post-intervention EF decrement. Accordingly, my thesis employed 10-min single bout manipulations of -30 mmHg and -50 mmHg lower-body negative pressure (LBNP) to determine whether a transient reduction in CBF impacts EF. LBNP was applied as it renders sub-atmospheric pressure to the lower limbs and redistributes blood from the upper to lower …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Eosinophilic Asthma Response To Therapy: 129xe Magnetic Resonance Imaging And Computed Tomography, Marrissa Joan Mcintosh

Electronic Thesis and Dissertation Repository

Novel biologic therapies, such as anti-interleukin-5 receptor α (anti-IL-5Rα) or benralizumab, have been developed to treat patients with severe eosinophilic asthma who experience frequent exacerbations, poor quality of life and increased risk of mortality. Whether this therapy results in disease modifying activity, specifically in the asthmatic airways and pulmonary vasculature, is still poorly understood. Pulmonary structure and function may be evaluated using computed tomography (CT) and hyperpolarized noble gas magnetic resonance imaging (MRI), respectively. Computed tomography has previously been utilized to measure airway dimensions, mucus occlusions and pulmonary blood volumes. In contrast, hyperpolarized gas MRI allows for the in vivo …

The Sympathetic Neural Control Of The Circulation At Rest And During Exercise: Effects Of Age, Biological Sex, And Sex Hormones, Andrew W. D'Souza

Electronic Thesis and Dissertation Repository

The overall objective of this dissertation was to determine the impact of age, sex, and sex hormones on the discharge behaviours of muscle sympathetic action potentials (APs) as well as the corresponding changes in peripheral vasoconstriction and blood pressure at rest and during exercise. The microneurographic technique was employed to record multi-unit muscle sympathetic nerve activity (MSNA), with a continuous wavelet transform applied post-hoc to evaluate APs within the recorded neurogram. Study One examined the impact of aging on the central and peripheral arcs of the sympathetic baroreflex under resting conditions. This study revealed that middle-aged-to-older adults demonstrated heightened sympathetic …

Water-Fat Magnetic Resonance Imaging For The Assessment Of Human Fetal Adipose Tissue, Stephanie A. Giza

Electronic Thesis and Dissertation Repository

Adipose tissue is crucial for providing heat and energy to infants, especially at transitions such as birth and therefore must begin developing in utero. This development may be altered due to an adverse uterine environment, increasing the risk of developing later-life metabolic diseases such as obesity. An early assessment of fetal adipose tissue development through lipid accumulation could be key to understanding metabolic programming and minimizing this risk.

Water-fat magnetic resonance imaging (MRI) can non-invasively measure the lipid concentration of tissues and can therefore monitor the development of adipose tissue via tissue lipid concentration. This work demonstrated the feasibility …

Predicting Brain Metastasis Response To Stereotactic Radiosurgery Using Magnetic Resonance Imaging Radiomics And Machine Learning, David A. Devries

Electronic Thesis and Dissertation Repository

Brain metastases (BMs) represent advanced cancer, and so BM patients must be treated quickly and effectively while minimizing treatment toxicities. Stereotactic radiosurgery (SRS) uses conformal, ablative radiation doses to treat BMs, but with failure rates up to 30%. A predictive model of BM progression post-SRS would therefore aid in BM treatment selection and SRS planning. Previous studies have used pre-treatment T1-weighted contrast-enhanced magnetic resonance imaging (T1w-CE MRI) to predict SRS outcomes, through quantitative radiomic analysis with machine learning (ML) and qualitative appearance analysis. Comparison of these methods is not well understood, and ML methods have not been studied for sensitivity …

A Computational Model Of Multiple Interconnected Capillary Modules In Skeletal Muscle, Raashi Vijay

Electronic Thesis and Dissertation Repository

Background: Skeletal muscle (SM), with its precise O₂ supply-demand matching, is ideal for studying microvascular (MV) function, which is crucial in cardiovascular physiology and disease. Our goal is to gain understanding of SM microcirculation using recent capillary network module (CM) data from rat in a computational model.

Methods: We construct a 4-CM network, with single-vessel equivalents for each CM, three arterioles, and two venules. A two-phase (plasma/RBCs) steady-state model is used to calculate blood flow. An iterative boundary pressure finding method is developed to match flow in CMs.

Results: We validate our flow and pressure models …

Metabolomic Biomarkers For Hypertensive Disease Of Pregnancy, Akasham Rajagopaul

Electronic Thesis and Dissertation Repository

Hypertensive disease of pregnancy (HDP) is a serious cardiometabolic pregnancy complication. Early onset HDP (EO-HDP) is more severe but rare, whereas late onset HDP (LO-HDP) is milder but common. Current disease markers, including placental growth factor (PlGF), are reasonable predictors of EO-HDP but poor predictors of LO-HDP. We sought to assess the performance of metabolomic biomarkers in HDP through a scoping review and primary analysis of plasma from symptomatic patients. Review of 31 studies indicated better prediction of all HDP and EO-HDP than LO-HDP using metabolomic biomarkers. Due to substantial heterogeneity in reported metabolites, no set of reliable biomarkers have …

Assessment Of A Novel High-Density, Full-Head Coverage, Time-Resolved Near-Infrared Spectroscopy (Nirs) Device For Intraoperative Neuromonitoring, Farah Kamar

Electronic Thesis and Dissertation Repository

Neuromonitoring during surgery is used to detect early indications of cerebral injury before permanent damage occurs. A commonly used technology is cerebral oximetry; however, current systems only monitor one brain region and have limited depth sensitivity. A newly developed NIRS system, Kernel Flow, offers the possibility to address both limitations by providing full-head coverage and time-resolved detection to enhance sensitivity to the brain. This work aimed to assess Kernel Flow’s sensitivity to regional cerebral oxygenation changes. Two experiments were conducted. In the first, decreases in cerebral oxygenation caused by transient carotid compression were measured in healthy volunteers. The second was …

In Utero Magnetic Resonance Relaxometry For Fetal Tissue Development, Simran Sethi

Electronic Thesis and Dissertation Repository

Fetal life is a significant period of human development because organ systems that sustain life outside the uterus begin to develop during this time. A necessary process that begins during fetal life is myelination, which is the process by which myelin, a lipid-rich substance, is wrapped around neurons in the brain to increase the speed of action potential transmission. Since myelination is critical for the normal function of the central nervous system, fetal myelin assessment is important for understanding neurodevelopment and neurodegeneration, such as intrauterine growth restriction (IUGR).

Magnetic resonance imaging (MRI) is an excellent tool for visualizing fetal anatomy …

Development And Validation Of Mechatronic Systems For Image-Guided Needle Interventions And Point-Of-Care Breast Cancer Screening With Ultrasound (2d And 3d) And Positron Emission Mammography, Claire Ks Park

Electronic Thesis and Dissertation Repository

The successful intervention of breast cancer relies on effective early detection and definitive diagnosis. While conventional screening mammography has substantially reduced breast cancer-related mortalities, substantial challenges persist in women with dense breasts. Additionally, complex interrelated risk factors and healthcare disparities contribute to breast cancer-related inequities, which restrict accessibility, impose cost constraints, and reduce inclusivity to high-quality healthcare. These limitations predominantly stem from the inadequate sensitivity and clinical utility of currently available approaches in increased-risk populations, including those with dense breasts, underserved and vulnerable populations.

This PhD dissertation aims to describe the development and validation of alternative, cost-effective, robust, and high-resolution …

Advancing Non-Invasive Imaging Techniques For Tracking Cellular Therapeutics In Vivo, Olivia C. Sehl

Electronic Thesis and Dissertation Repository

Cell therapies, including mesenchymal stem cells (MSC) and regulatory T cells (Tregs) have shown potent and long-lasting therapeutic benefit in several disease applications. Unfortunately, the effectiveness of these therapies is variable and following administration, it is largely unknown where therapeutic cells traffic and how many persist over time. This thesis aims to advance and compare iron- and fluorine-19 (¹⁹F)-based magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) for therapeutic cell tracking.

First, we developed a trimodal imaging approach to study MSC fate in vivo. In a mouse model, iron-labeled MSC were detected by MRI and MPI, …

Development Of Magnetic Particle Imaging For Quantitative Immune Cell Tracking, Julia J. Gevaert

Electronic Thesis and Dissertation Repository

The Foster lab has been developing cellular MRI tools for well over a decade using superparamagnetic iron oxide (SPIO)-based contrast agents for numerous applications cell tracking applications. SPIO are used to label cells which are indirectly detected as regions of signal loss. The main challenge with this technique is quantification of cell number, which is important for applications such as dendritic cell (DC)-based immunotherapies where cell number is used as a predictor of immunotherapeutic response.

Magnetic particle imaging (MPI) is a novel pre-clinical modality that shows promise for cell tracking. MPI directly detects the nonlinear magnetization response of superparamagnetic iron …

Effect Of Acute Exercise On Muscle And Liver Glucose Metabolism In T1dm Rodents, Justin A. Camenzuli

Electronic Thesis and Dissertation Repository

Individuals with Type I Diabetes Mellitus (T1DM) are at an increased risk for developing secondary complications which increases their risk of premature death. While the risk of secondary complications is reduced with intensive insulin treatment (IIT) and aerobic exercise (AE), both interventional strategies increase the risk of hypoglycemia. This study examined the effects of a 60-min bout of forced treadmill AE on hepatic and muscular blood glucose (BG) metabolism. Nineteen Sprague-Dawley rats were divided into two groups: Sedentary Control Rats (SC; n=5), and Sedentary T1DM rats (DSC); T1DM rats were subcategorized into Diabetic Pre-Exercise (DPRE; n=14) and Diabetic Post-Exercise (DPOST; …

In Vivo Multi-Modal Imaging Approaches For Cancer, Stem And Immune Cells, Nourhan Shalaby

Electronic Thesis and Dissertation Repository

Introduction: Molecular imaging allows for non-invasive longitudinal visualization of cellular functions in vivo. This area of research has provided better understanding of fundamental molecular and biochemical processes, enabled optimization of pre-clinical and clinical assessments for new treatments, and allowed for more accurate and early detection of many pathologies. Extensive research for novel imaging techniques and emerging technologies have rapidly advanced the field. However, an ideal single imaging modality or approach does not exist. Alternatively, multi-modal imaging approaches are commonly applied to overcome limitations of individual technologies. In this thesis, we design, develop, validate, and image various cell types using …

Investigating Cellular Imaging Techniques For Cancer Cell Tracking, Natasha Knier

Electronic Thesis and Dissertation Repository

Introduction: Breast cancer remains a leading cause of mortality among women due to the propensity of breast tumours to spread and metastasize to distant sites, including the brain. Early detection of metastatic disease has been challenging, and typical methods of treatment often fail. A significant roadblock in advancing the detection and treatment of breast cancer brain metastases is the lack of representative experimental preclinical models and methods of studying its progression in vivo. Methods: First, we use iron-based cellular MRI to noninvasively track the progression of a brain metastatic breast cancer cell line in murine models with varying immune …

Investigating The Role Of Mirna-378-3p And Its Target Pdia-4 In Endothelial Cells, Shuhan Bu

Electronic Thesis and Dissertation Repository

Endothelial cells (ECs) line the innermost layer of blood vessels and maintain vascular homeostasis. Endothelial dysfunction may lead to cardiovascular diseases (CVDs) such as atherosclerosis. Autophagy maintains cellular homeostasis by degrading and recycling unused proteins for its’ reuse. Impaired endothelial autophagy is reported in CVDs. MicroRNAs are non-coding RNAs which regulate autophagy and endothelial function. However, the exact role of miRNA in endothelial autophagy and function is unknown. To this aim, we identified miR-378-3p as the most upregulated miRNA in autophagy-deficient ECs via miRNA-array. Inhibition and activation of autophagy up- and down-regulated miR-378-3p expression, respectively. MiR-378a-3p overexpression or inhibition inversely …

Evaluating The Biomechanical, Functional, And Clinical Outcomes Of Bicruciate Stabilized Total Knee Arthroplasty, Jordan S. Broberg

Electronic Thesis and Dissertation Repository

Total knee arthroplasty (TKA) is the only solution for treating arthritis of the knee joint. Although it is successful at reducing pain and returning function to affected joints, one in five patients still report dissatisfaction following their operation. Bicruciate stabilized (BCS) TKA was developed to improve outcomes by replicating normal knee structure and function. The biomechanical, functional, and clinical outcomes for the BCS design were investigated in this thesis through radiographic imaging techniques, wearable sensor systems, and questionnaires in a cohort of TKA patients.

A stereo x-ray technique, called radiostereometric analysis (RSA), assesses implant fixation by tracking micromotion of TKA …

Building A Magnetosome-Like Nanoparticle For Magnetic Resonance Imaging, Qin Sun

Electronic Thesis and Dissertation Repository

With its superb spatial and temporal resolution, magnetic resonance imaging (MRI) has great potential to track cellular activities that define early stages of disease. To improve molecular imaging techniques, we are developing MRI reporter gene expression based on the magnetosome. In magnetotactic bacteria (MTB), magnetosome formation compartmentalizes iron biominerals in membrane-enclosed vesicles. We hypothesize that essential magnetosome proteins interact in any cell type to form rudimentary magnetosome-like nanoparticles, providing a genetically-controlled contrast agent for molecular MRI.

MTB genes mamE, mamB, mamI, and mamL were cloned from M. magneticum sp. AMB-1 genomic DNA by PCR and inserted into …

Novel 129xe Magnetic Resonance Imaging And Spectroscopy Measurements Of Pulmonary Gas-Exchange, Alexander M. Matheson

Electronic Thesis and Dissertation Repository

Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy.

In vivo Xenon-129 gas-exchange magnetic resonance imaging (¹²⁹Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized ¹²⁹Xe gas, it …

Longitudinal Computed Tomography Airway Measurements In Ex-Smokers With And Without Chronic Obstructive Pulmonary Disease, Paulina V. Wyszkiewicz

Electronic Thesis and Dissertation Repository

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic airflow obstruction, emphysematous destruction, and airway remodeling. Thoracic CT has previously revealed abnormalities in the small airways, where disease onset is believed to initiate. In previous COPD cohort studies, airway wall thinning and diminished total airway count (TAC) were observed with increasing disease severity. However, longitudinal insights are lacking. Accordingly, the objective of this thesis was to evaluate longitudinal CT airway measurements at baseline and after three-years in ex-smokers. I observed that CT TAC was decreased only in ex-smokers with COPD, whilst airway walls were thinner in both …

An Evaluation Of A Deep Learning Approach For Radiation Dose Reduction In 18f-Fdg Pet/Mri Pediatric Epilepsy Imaging, Confidence Raymond

Electronic Thesis and Dissertation Repository

Epilepsy is a degenerative brain disease characterized by abruption of neural activities that result in seizures. The onset of epileptic seizures are usually from a primary source - the epileptogenic foci (EF) which could be distributed to nearby neurons and tissues. Accurate localization of EF is critical in epilepsy cases where drug treatment has failed, and surgery is indicated to resect the EF to alleviate seizure. Typically, hybrid positron emission tomography (PET) and computed tomography (CT) imaging are performed to functionally localize the EF in drug-resistant epilepsy for surgical planning when anatomical abnormalities representing the EF cannot be identified on …

Secretion Of Salivary Proteins And Their Interactions, Karla Tonelli Bicalho Crosara

Electronic Thesis and Dissertation Repository

Saliva’s clinical application for disease diagnosis and monitoring is limited by incomplete knowledge of salivary protein interactions, the effect of stimulation on the salivary proteome, and if these factors impact protein identification. This thesis expands knowledge of the salivary interactome and effects of stimulation intensity and duration on parotid saliva’s proteome. First, previous in vitro studies identified 43 proteins in the histatin 1-protein network and demonstrated histatin 1’s increased stability in whole saliva when interacting with amylase. We hypothesized that protein-protein-interaction databases could enlarge the histatin 1-protein network. A comprehensive histatin 1-protein network was created using STRING database, merging previous …

Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (²³Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and …

Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang

Electronic Thesis and Dissertation Repository

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in …

Postexercise Executive Function Benefits And Cerebral Blood Flow: In The Lab And At Home, Benjamin Tari

Electronic Thesis and Dissertation Repository

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO₂) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes …