Medical Sciences Commons^™

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 …

Resolving The Longitudinal Triglyceride Phenotype Of Heterozygous Lpl And Apo A-V Deficiency, Shehan D. Perera

Electronic Thesis and Dissertation Repository

Hypertriglyceridemia (HTG) is a risk factor for cardiovascular disease. However, only the triglyceride (TG) phenotype produced by biallelic loss-of-function (LOF) variants in the canonical TG metabolism genes is well understood. The TG phenotype produced by monoallelic LOF variants is poorly understood. We aimed to evaluate the TG phenotype associated with monoallelic LOF variants in the canonical TG metabolism genes.

Next-generation sequencing panel was employed to identify patients heterozygous for LOF variants in two of the canonical TG metabolism genes LPL and APOA5, followed by chart review to determine baseline and longitudinal TG phenotype in these patients.

My findings suggest …

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 …

Share Cannabidiol Exposure During Gestation Leads To Adverse Cardiac Outcomes Early In Postnatal Life In Male Rat Offspring., Daniel B. Hardy, Steven R. Laviolette, Kendrick Lee, David Rc Natale

Physiology and Pharmacology Publications

Introduction: Studies indicate that *7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to D9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30mg/kg CBD or vehicle control i.p. daily from …

Cannabidiol Exposure During Rat Pregnancy Leads To Labyrinth-Specific Vascular Defects In The Placenta And Reduced Fetal Growth, Daniel B. Hardy, David R C Natale, Kendrick Lee

Physiology and Pharmacology Publications

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as ‘‘natural’’ and ‘‘safe’’ as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of D9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat …

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 …

The Impact Of Simulated Image Acquisition Time Reduction On Image Quality And Parameters Of Myocardial Perfusion Imaging Using A Dedicated Cardiac Camera, Alireza Khatami

Electronic Thesis and Dissertation Repository

Heart disease is the second leading cause of death in Canada, highlighting the crucial role of early diagnosis in disease management. Myocardial perfusion imaging (MPI), is widely employed for this purpose, involves injecting a radiopharmaceutical into the body, imaging its distribution with a gamma camera, and revealing cardiac blood flow patterns. A significant challenge in MPI is the lengthy 8 to 10 minutes required for stress and rest imaging, potentially causing patient discomfort and compromising image quality due to movement. In a clinical study with 26 patients, post-processed data manipulation simulated a reduction in MPI imaging time. The findings indicated …

Development Of Ph-Weighted Magnetic Resonance Imaging In The Spinal Cord: Application In Degenerative Cervical Myelopathy, Alicia E. Cronin

Electronic Thesis and Dissertation Repository

Degenerative cervical myelopathy (DCM) is a degenerative disease of the spinal cord that can lead to neurological dysfunction. It has been hypothesized that ischemia and hypoxia in the spinal cord at the site of compression could impact functional recovery after decompression surgery. Unfortunately, direct in-vivo quantification of hypoxia and ischemia in the spine has been limited in humans. Magnetic resonance imaging (MRI) can be utilized to measure hypoxia indirectly in soft tissue. Specifically, chemical exchange saturation transfer (CEST) is an MRI contrast that can be derived from the transfer of magnetization from selectively excited endogenous protons to bulk water protons. …

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 …

Investigating The Effects Of Infantile Hydrocephalus On Visuomotor Integration: A Study Utilizing Behavioural And Neuroimaging Analyses, Derya Adil

Electronic Thesis and Dissertation Repository

This thesis describes studies which explore the impact of infantile hydrocephalus on the posterior cortex, specifically focusing on the parietal and occipital lobes. Using resting-state functional MRI, the functional connectivity within the visuomotor integration network was investigated and connectivity was traced through the corpus callosum. We hypothesized that children with hydrocephalus would demonstrate altered functional connectivity compared to typically developing controls. Our findings revealed that patients had reduced functional connectivity in visuomotor pathways, particularly the inferior frontal occipital fasciculus, superior longitudinal fasciculus, and the frontal aslant tract, with notable impact on the left and right fusiform gyrus and precuneus. We …

Role Of Circular Rna Asph In Macrophage Polarization And Response In Sepsis, Tan Ze Wang

Electronic Thesis and Dissertation Repository

Circular RNAs (circRNAs), a novel non-coding RNA species generated by back-splicing, has been shown to participate in gene regulation of leukocytes. Our previous RNA sequencing results show circular RNA ASPH (circASPH) to be highly expressed in peripheral blood mononuclear cells of sepsis patients at the start of intensive care. Macrophages, as ubiquitous innate immune cells, are responsible for the recruitment of other immune cells at sepsis onset. This work investigates the role of circASPH in the regulation of macrophage polarization in sepsis. Using an in vitro THP-1 cell model, it was found that circASPH levels peaked after 24 h of …

Assessing The Sensitivity Of Cerebral Blood Flow And Oxygenation To High Intracranial Pressure With Near-Infrared Light, Sule Karagulleoglu Kunduraci

Electronic Thesis and Dissertation Repository

Premature birth is associated with increased susceptibility to cerebral injuries because of the compounded effects of underdeveloped cerebral vascular and unstable hemodynamics. Notably, premature infants are highly vulnerable to intraventricular hemorrhage, which often leads to hydrocephalus and subsequently to high intracranial pressure (ICP). Current monitoring methods such as ultrasonography can only detect injuries that have already occurred, highlighting the need for prognostic tools. We hypothesize that concomitant measures of cerebral blood flow (CBF), blood oxygenation, and oxygen metabolism will be sensitive to high ICP. To test this hypothesis, experiments were conducted in a piglet model of high ICP using a …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

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 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 …

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 …

Neuropsychological Outcomes After Cardiac Surgery: A Pilot Feasibility Study, Sydni G. Paleczny

Electronic Thesis and Dissertation Repository

Approximately half of patients who have cardiac surgery will experience deficits in attention, memory, and thinking speed after their operation. Given that heart surgery is one of the most common medical procedures in Canada, it is necessary to better understand the natural history of cognitive impairment after such surgery. Yet, there is no globally accepted method for measuring cognitive function in patients who undergo heart surgery. To address this, we assessed whether it was feasible to use a web-based approach to measure cognition in heart surgery patients before and after their operation. Findings showed that remote administration of cognitive testing …

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 …

Mechanisms Underlying Stem Cell Depletion In Ageing., Mackenzie Hsu

Electronic Thesis and Dissertation Repository

As we age, our bodies lose the ability to repair damaged tissues. This impairment may be due to age-related deficits in our regenerative stem cells. Stem cells reside in specialized areas called stem cell niches. Ageing may cause alterations in the stem cells directly or may alter the stem cell niche to generate deficits. However, systematic studies mapping stem cell deficits and alterations to stem cell niche are lacking. Here, I investigated the bone marrows of young and aged mice to determine age-related changes in the microenvironment that may alter resident stem cells.

To achieve my research objective, I examined …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

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 …

Investigating The Role Of Endothelial Breast Cancer Susceptibility Gene 2 In Doxorubicin-Induced Cardiotoxicity, Berk U. Rasheed

Electronic Thesis and Dissertation Repository

Doxorubicin (Dox) is a chemotherapeutic drug used to treat various malignancies including breast and ovarian cancers. Accumulating evidence implicates cardiac impairments associated with Dox treatment. The Breast Cancer Susceptibility Gene 2 (BRCA2) functions to maintain genome-wide stability by promoting DNA-damage repair. Accordingly, cardiomyocyte damage is specifically regulated by contributors of DNA damage repair such as BRCA2. The endothelium, the innermost cells of every blood vessel, act to protect our tissues from noxious elements, however, recent evidence suggests that BRCA2 knockdown compromises endothelial cell function. A putative role of endothelial BRCA2 during Dox-induced cardiotoxicity (DIC) remains unknown. We hypothesized that endothelial-specific …

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 …

Inflammation In The Neovaginal Microenvironment Of Transfeminine Individuals, Hannah M.J. Wilcox

Electronic Thesis and Dissertation Repository

Transfeminine individuals are assigned male at birth but do not identify as male. Some transfeminine individuals may choose to undergo the gender affirming surgery vaginoplasty to create a neovagina. There is a paucity of data on the neovaginal microenvironment to inform best gynecological practices. Vaginal and penile inflammation is modulated by local microbiota, but drivers of inflammation in the neovagina are poorly understood. The compositions of the neovaginal microbiota and immune milieu were elucidated from neovaginal swabs, using 16s rRNA gene sequencing and multiplex immunoassay, respectively. Immune data reduction and clustering was performed, and six unique immune profile types (IPTs) …

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, …