Medical Specialties Commons^™

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 …

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 …

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 …

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Vertebral Endplate Structural Defects: Measurement, Prevalence And Associated Factors, Aliyu Lawan

Electronic Thesis and Dissertation Repository

Objective: To synthesize current knowledge on the association of endplate structural defects (EPSD) with back pain (BP), improve EPSD measurement, and investigate EPSD prevalence, distribution, and association with age and body mass index (BMI).

Methods: In study 1, a systematic review was conducted on five databases for studies reporting on the association between EPSD and BP. Studies 2 and 3 used CTs and mCTs of 19 embalmed cadavers to examine the diagnostic accuracy of common EPSD assessment methods, and to develop and validate a novel method. Study 4 used the novel method on 200 adult males’ MRI to estimate EPSD …

Improving The Reliability And Accessibility Of Ct Perfusion Imaging In Acute Ischemic Stroke, Kevin J. Chung

Electronic Thesis and Dissertation Repository

CT perfusion (CTP) imaging is a validated treatment decision support tool in acute ischemic stroke. Automated analysis of CTP cerebral blood flow (CBF) and Tmax maps produces estimates of ischemic core and penumbra volumes used to determine target mismatch profiles for treatment. However, availability and utilization of CTP is low due to diagnostic variability between CTP software and technical, logistical, and radiation dose considerations that may limit its routine adoption. The objective of this doctoral research was to improve the reliability and accessibility of CTP by (1) improving diagnostic agreement between CTP software, (2) enabling perfusion imaging with standard acute …

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …

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 …

Exploration Of The Pathophysiological Mechanisms Underlying Hemodialysis Associated Cardiac Ischemic Injury, Lisa Yun Jeong Hur

Electronic Thesis and Dissertation Repository

Hemodialysis (HD) provides life-saving treatment in individuals with kidney failure. However, HD is associated with poor quality of life and extremely high mortality rates mainly caused by cardiovascular disease due to heart failure and sudden cardiac death. Standard pharmacological treatment developed within the non-kidney disease community are largely ineffective in HD patients because of the difference in pathophysiology of cardiovascular mortality. HD treatment causes hypotension and recurrent ischemic injury to multiple vascular beds including the heart, leading to heart failure. These injuries can be abrogated by improving the patient’s tolerability of the treatment. To apply interventions that may improve hemodynamic …

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

Multi-Scale Computational Modeling Of Coronary Blood Flow: Application To Fractional Flow Reserve., Jermiah Joseph

Electronic Thesis and Dissertation Repository

Introduction. Fractional flow reserve (FFR) is presently an invasive coronary clinical index. Non-invasive CT imaging combined with computational coronary flow modelling may reduce the patient’s burden of undergoing invasive testing.

Research statement. The ability to obtain information of the hemodynamic significance of detected lesions would streamline decision making in escalation to invasive angiography.

Methods. A reduced order (lumped parameter) model of the coronary vasculature was further developed. The model was used in the assessment of the roles of structure and function on the FFR. Sophisticated methods were used to elicit numerical

solutions. Further, CT imaging (n = …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

The Molecular Landscape Of Early-Stage Breast Cancer With Lymph Node Metastasis, Farhad Ghasemi

Electronic Thesis and Dissertation Repository

Axillary lymph nodes (ALNs) are the primary site of metastasis in breast cancer, and their involvement has implications in disease staging, prognostication, and treatment decisions. A non-invasive modality of assessing the risk of ALN metastasis can improve care in patients with early-stage breast cancer by omitting the morbidity and costs associated with axillary surgery.

This thesis explores the molecular landscape of early-stage breast cancers with ALN metastasis and shows the potential of tumour molecular signatures in predicting ALN involvement. After a systematic review of the literature, we use data from The Cancer Genome Atlas (TCGA) to develop molecular signatures correlated …

Quantitative Mri And 3d-Printing For Monitoring Periprosthetic Joint Infection, Greg Hong

Electronic Thesis and Dissertation Repository

Joint replacements are becoming increasingly commonplace with over 130,000 joint arthroplasties being performed annually in Canada. Although joint replacement surgery is highly successful, implants do occasionally fail and need to be replaced via costly and difficult revision surgery. Periprosthetic joint infection (PJI) has recently become the leading reason for revision of both hip and knee replacements, which is unfortunate because PJI is difficult to diagnose and treat effectively; diagnosis is made particularly difficult by the lack of established non-invasive (imaging) means of evaluating PJI. This thesis aims to demonstrate that magnetic resonance imaging (MRI) has potential for diagnosing and monitoring …

The Role Of Urinary Modulators In The Development Of Infectious Kidney Stones, Brendan Wallace

Electronic Thesis and Dissertation Repository

The pathogenesis of infectious kidney stones is poorly understood, while equally unclear is the role of urinary modulators and bacteria. An experimental model was created and utilized to test a variety of urinary modulators and bacterial strains commonly associated with struvite and calcium phosphate stones to evaluate their potential roles in influencing crystal formation. Modulators such as acids, citrate, and osteopontin had strong inhibitory effects on infectious crystal formation while the remaining modulators had neutral, mixed, or positive effects. Lastly, it was determined that the presence of urease may not directly lead to calcium phosphate and struvite stones in all …

The Role Of Coagulase-Negative Staphylococcal Secreted Products On Staphylococcus Aureus And Staphylococcus Lugdunensis Infections, Denny Chin

Electronic Thesis and Dissertation Repository

The Staphylococcus genus is comprised of over 40 bacterial species. The most well-studied species in this genus is the notorious human pathogen Staphylococcus aureus, a bacterium that produces coagulase among many other virulence factors. Since S. aureus is a major health burden and causes a plethora of diseases in humans, it has received significant attention and much research has been done to understand its biology to treat diseases caused by this pathogen. However, the coagulase-negative staphylococci (CoNS) make up most of the staphylococcal species and have received less attention since they are thought to have a lesser impact on …

Delineation Of Ascending Aortic Medial Degeneration Using Diffusion Tensor Imaging, Justin A. Ching-Johnson

Electronic Thesis and Dissertation Repository

Thoracic aortic aneurysms (TAAs) are a life-threatening dilation of the thoracic aorta that can lead to catastrophic dissection or rupture. In TAAs, the structure of the aortic wall is perturbed. Current imaging approaches assess lumen dimensions but lack the ability to delineate aortic wall architecture, a key determinant of aortic integrity. Diffusion tensor imaging (DTI) is an MRI modality which can reveal tissue microstructure through diffusion characteristics. In this thesis I investigated the potential for DTI to evaluate TAA architecture. A porcine model of aortic wall degeneration was developed, and DTI scans were performed on healthy and degenerated porcine ascending …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Is There An Increased Risk Of Delirium Among Patients With Overactive Bladder Treated With Newer Anticholinergic Medication Compared To A Beta-3 Agonist?, Khaled Ashraf Etaby

Electronic Thesis and Dissertation Repository

ABSTRACT

Objective

To determine if there is an increased risk of delirium among patients with overactive bladder (OAB) started on anticholinergic medication compared to beta-3 agonist.

Methods

We conducted a population-based, retrospective, matched weight cohort study using administrative data from Ontario, Canada from January 2016 until March 2020. We matched 13865 new users of Oxybutynin to 33097 new users of newer anticholinergic medications (Solifenacin, Tolterodine, Trospium, Darifenacin and Fesoterodine), and to 56062 new users of beta-3 agonist medication (Mirabegron); all of the included medications are only for the treatment of OAB. Matching weights (an extension of the propensity score weighting) …

Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky

Electronic Thesis and Dissertation Repository

Both metabolic and cognitive dysfunction can originate from fetal reprogramming precipitating from adverse conditions experienced in utero. Of note is the western diet (WD), which is associated with maternal energy imbalances that may hinder fetal development through altered placental function. Brain-derived neurotrophic factor (BDNF), a growth factor that supports the placenta and developing brain, is responsive to such energy imbalances. This study sought to investigate the impact of lifelong maternal WD consumption on fetoplacental development, focusing on relations between placental changes, and fetal growth and neurodevelopment in a guinea pig model. Maternal WD consumption resulting in a lean metabolically …

Measuring Inflammation In The Entire Myocardium In A Canine Model Of Myocardial Infarction With Hybrid Pet/Mri, Benjamin Wilk

Electronic Thesis and Dissertation Repository

Background: After myocardial infarction (MI), fibrosis and an ongoing dysregulated inflammatory response are associated with adverse cardiac remodeling. Fluorodeoxyglucose (FDG) positron emission tomography (PET) is sensitive to inflammation provided suppression protocols are implemented to restrict the uptake of glucose in myocytes. Magnetic resonance imaging can be used to determine extracellular volume, a surrogate measure of fibrosis. In some cases, patients present with markedly reduced flow in the setting of a large infarct, i.e. microvascular obstruction, restricting the delivery of FDG and contrast agents. To overcome this problem, a constant infusion was explored as an alternative to the clinical standard bolus …

Testing A Novel Peptide-Infused Cream For Treatment Of Rheumatoid Arthritis In Dr4tg Mice, Alisha J. Moynahan

Electronic Thesis and Dissertation Repository

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint pain and damage. Studies have shown that inducing immune tolerance towards RA-specific proteins/peptides in RA mouse models can reduce arthritis severity and pro-inflammatory responses. The objectives of this study were to determine if a novel peptide cream treatment could modify RA-specific immune responses and reduce joint swelling in a humanized mouse model expressing the HLA-DRB1*0401 allele (known as DR4tg mice), the strongest genetic risk-factor for RA. Hyaluronan-Phosphatidylethanolamine cream infused with synthetic peptides HomoCitJED and CitJED was applied to HomoCitJED-immunized DR4tg mice before or after arthritis induction. Knee joint …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

Evaluating Anesthetic Protocols For Non-Human Primate Functional Neuroimaging, Megha Verma

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to measure a proxy of neural activity in vivo with high spatial specificity. One subject can be followed for a long period of time to assess changes in functional brain organization. However, fMRI is extremely sensitive to motion. The challenges of training non-human primates to reduce motion in an MRI scanner motivate the study of anesthesia which is commonly used to substitute for this training. In this thesis, I compare three different commonly used anesthetic protocols: isoflurane, propofol-fentanyl in combination, and fentanyl alone, to test which of …

Impact Of Graded Passive Cycling On Hemodynamics, Cerebral Blood Flow, And Heart Function In Healthy Adults And Septic Icu Patients, Jennifer Chen

Electronic Thesis and Dissertation Repository

Sepsis is a life-threatening dysregulation of host response to an infectious insult, which often leads to multi-organ failure. Sepsis survivors suffer from post-intensive care syndrome in part due to their prolonged bed rest and lack of mobility. Although early mobilization has been championed as a mechanism to counter the adverse effects associated with ICU immobility, due to sedation and mechanical ventilation, active early mobilization is not often administered in septic patients due to worries of hemodynamic instability and potential for inducing adverse events. Passive exercise is a mobilization modality that circumvents the need for patients to be conscious and participatory …

A Clinically Representative Rat Model Of Hip Hemiarthroplasty, Adam Dm Paish

Electronic Thesis and Dissertation Repository

Joint replacement is an increasingly common surgery with over 130,000 procedures performed annually in Canada. Although joint replacement surgery is highly successful, implants do not last a lifetime, and often have to be replaced via costly revision surgeries. Before innovations aimed at extending the life of implants are applied to the clinic, testing must be performed in animal models. Clinically representative small-animal models of joint replacement would be ideal in the initial stages of research and development, due to ease of handling and low costs, but few such models have been established in the literature. Thus, we describe the development …