Medical Sciences Commons^™

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 …

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 …

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 …

Spatiotemporal Optimization Of Intratumoural Electric Field Modulation For Cancer Therapy, Erin Iredale

Electronic Thesis and Dissertation Repository

The use of anti-cancer non-ablative electric fields is an expanding area of research that includes clinically available external devices for the treatment of glioblastoma (GBM), and a pre-clinical internal system called Intratumoural Modulation Therapy (IMT). IMT uses multiple electrodes implanted within the tumour to apply low intensity electric fields (~1 V/cm) focused on the target region, anywhere in the brain, with no externally visible devices. In this thesis, multi-electrode spatiotemporally dynamic IMT is investigated through computer simulation, numerical optimization, brain phantom and in vitro validation methods. These planning and validation strategies are hypothesized to improve tumour coverage with the necessary …

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 …