Digital Commons Network^™

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 …

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 …

Simulated And Experimental Approaches To The Development Of Novel Test Phantoms For Radiofrequency Heating Of Implanted Medical Devices, Amgad M. Louka

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) has cemented itself as the gold standard for imaging of soft tissues and is only increasing in popularity. Given the rising number of MRI scanners and medical device being implanted into patients, it is becoming increasingly likely that patients undergoing MRI will have an implanted medical device (IMD). The presence of an elongated metallic IMD inside a scanner could result in dangerous interactions with the radiofrequency fields during MRI, thus some of these IMDs preclude the patients from being scanned.

Orthopedic devices typically fall into this category due to their high potential for RF induced heating, …

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 …

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 = …

Anatomical And Functional Lung Imaging With Volumetric Computed Tomography In Non-Small Cell Lung Cancer, Heather Young

Electronic Thesis and Dissertation Repository

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. A significant challenge in treating NSCLC is balancing aggressive treatment with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges. 4-dimensional computed tomography (4D-CT) is an important part of motion management, but images often suffer from motion-induced artifacts. Volumetric CT scanners with wide axial field-of-view (aFOV) may reduce these artifacts and present an opportunity to advance CT-based functional lung imaging.

Chapter 2 presents a …

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, …

Atrial Fibrillation And Cognitive Decline: A Computational Hemodynamics Investigation, Timothy J. Hunter

Electronic Thesis and Dissertation Repository

Background: Atrial fibrillation (AF) is a prevalent cardiac disease which has been associated with increased risk of dementia and cognitive decline. We hypothesize that atrial fibrillation leads to regional transient hypoperfusion events in the brain, and that geometric variations in the arterial structure called the Circle of Willis (CoW) play a role in these events.

Methods: A computational model was developed to simulate cerebral blood flow in six common variations of the CoW. Risk was assessed based on frequency of beat-wise regional hypoperfusion events during AF, and sensitivity analysis was performed with respect to this model output.

Results …

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 …

A Two-Layer Continuous-Capillary Oxygen Transport Model: Development And Application To Blood Flow Regulation In Resting Skeletal Muscle., Keith C. Afas

Electronic Thesis and Dissertation Repository

In skeletal muscle (SM), the microcirculation distributes blood flow to capillary networks to meet local oxygen (O₂) demand. Experiments using intra-vital video microscopy (IVVM) have quantified blood flow and O₂ supply in capillary networks, and using an O₂ exchange chamber have measured local changes in blood flow believed due to O₂-dependent regulation. However, IVVM is unable to simultaneously measure capillary O₂ supply and SM O₂ content, implying the need for theoretical models to understand how flow regulation and SM oxygenation interact. In this thesis, a novel blood-tissue O₂ transport model using …

The Effects Of Autophagy And Proteasomes On Tgfβ Signalling And Emt, Charles Brandon Trelford

Electronic Thesis and Dissertation Repository

Transforming growth factor-β (TGFβ) signalling regulates growth, proliferation, immunity, and development. Although TGFβ typically antagonizes tumour formation, tumour cells often acquire mutations within the TGFβ signalling pathway that activate epithelial-mesenchymal transition (EMT). During EMT, epithelial tumour cells lose epithelial-like properties and acquire mesenchymal-like characteristics, which allows tumour cells to detach from the primary tumour and establish metastatic colonies. In addition to EMT, TGFβ augments tumourigenesis by increasing the degradation of damaged macromolecules and organelles via autophagy. Autophagy contributes to radiotherapy and chemotherapy resistance by mitigating the damages inflicted on tumour cells. Currently, there is a growing interest in the relationship …

Prenatal Care Providers’ Experience With Pre-Test Counselling For Nipt In Ontario: Counselling Challenges And Support Required, Leichelle A. Little

Electronic Thesis and Dissertation Repository

Non-invasive prenatal testing (NIPT) is a prenatal test that has experienced unprecedented commercial development and transformed prenatal care. The Ontario Ministry of Health presently funds NIPT as a first-tier prenatal screening option for high-risk singleton pregnancies and all twin pregnancies. Individuals who do not qualify for public funding or would like to screen for additional conditions can pay for NIPT privately, starting at approximately $495-$550 (CA) for baseline panels. Prenatal care providers such as family physicians, maternal-fetal-medicine specialists, obstetrician-gynaecologists, residents, midwives and registered nurses have an increasingly important role in offering NIPT in Ontario. Although these healthcare professionals do not …

Software And Hardware-Based Tools For Improving Ultrasound Guided Prostate Brachytherapy, Nathan Orlando

Electronic Thesis and Dissertation Repository

Minimally invasive procedures for prostate cancer diagnosis and treatment, including biopsy and brachytherapy, rely on medical imaging such as two-dimensional (2D) and three-dimensional (3D) transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) for critical tasks such as target definition and diagnosis, treatment guidance, and treatment planning. Use of these imaging modalities introduces challenges including time-consuming manual prostate segmentation, poor needle tip visualization, and variable MR-US cognitive fusion. The objective of this thesis was to develop, validate, and implement software- and hardware-based tools specifically designed for minimally invasive prostate cancer procedures to overcome these challenges.

First, a deep learning-based automatic 3D …

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 …

Activatable Synthetic Biomarker Systems For Gene- And Cell-Based Cancer Detection And Theranostics, Tianduo Wang

Electronic Thesis and Dissertation Repository

Introduction: The ability to non-invasively detect cancer cells and other cell types within tumours has many valuable applications for early cancer diagnosis and grading, monitoring disease progression, and assessing treatment response. While technologies for detecting endogenous cancer biomarkers in bodily fluids or through imaging are being rapidly developed, they often face challenges that result in low sensitivity and/or specificity. To address these limitations, an emerging strategy involves building exogenously delivered tools that use reporter genes as synthetic biomarkers. Leveraging synthetic biology, reporter genes can be assembled into cancer-activatable gene circuits which link their expression to the presence of endogenous cancer …

Examining The Association Between Brain Mri Measures At 7 Tesla And Cognition Following Covid-19 Infection, Helma Heidari

Electronic Thesis and Dissertation Repository

The long-term neuropsychological, cognitive, and neurobiological effects of the severe acute respiratory syndrome (SARS-CoV-2) in survivors with milder symptoms are still poorly understood. In this thesis we evaluated cognitive and psychological changes approximately five weeks after a wide range of symptoms in COVID-19 illness and determined whether advanced diffusion magnetic resonance imaging measures within subcortical brain structures of the limbic system were related to neurological, respiratory, psychiatric, and gastric symptoms experienced during the acute phase of illness. Cognitive and neuropsychological evaluations were performed in 45 participants who experienced neurological symptoms during the acute phase of COVID-19 illness. Participants also underwent …

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 …

Magnetic Resonance Systems Development For Point-Of-Care Mri Platforms, Eric J. Lessard

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging utilizes electromagnets to produce anatomical images in both clinical and research settings. In the race towards increasing performance head-optimized scanners have begun playing a significant role in providing high quality imaging of the head. However, they are implemented using smaller geometries and as such fail to allow entrance of the patient past their shoulders. This is overcome by designing asymmetric gradient coils which have their imaging region located towards one end of the gradient coil, as opposed to the geometric center, allowing brain imaging. There exists interest in compact configurations which allow imaging further into the cervical …

Three-Dimensional Ultrasound Imaging For Characterization Of Synovitis In First Carpometacarpal Osteoarthritis, Carla Du Toit

Electronic Thesis and Dissertation Repository

First carpometacarpal osteoarthritis is one of the most common forms of OA and is a significant source of pain and disability for patients. Discrepancies between traditional imaging modalities and patient reported outcomes have led galvanized researchers to developing objective point of care based imaging tools for assessing OA progression and treatment response. This thesis aims to describe the development and validation of a semi-submerged mechanical three-dimensional ultrasound device against magnetic resonance imaging. The validation of the 3D US device was conducted on a series of imaging phantoms, as well as ten CMC1 OA patients. Two-raters manually segmented areas of synovial …

Impaired Efferocytosis In Knee Osteoarthritis, Luigi M. Del Sordo

Electronic Thesis and Dissertation Repository

Non-resolving synovial inflammation is present in both human and animal models and plays a key role in the pathogenesis of knee osteoarthritis (OA). However, it is not known how inflammation affects synovial macrophage function and if this contributes to the loss of tissue homeostasis. The purpose of this thesis was to understand the role of efferocytosis in knee OA. There is an increased apoptotic cell burden within the synovium of patients with late-stage knee OA. Synovial-derived macrophages from these patients exhibited impaired efferocytosis. Healthy blood-derived macrophages exposed to synovial fluid from patients with knee OA recapitulated the defective efferocytosis. Impaired …

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 …

Cost-Effective Non-Destructive Testing Of Biomedical Components Fabricated Using Additive Manufacturing, Santiago Fabian Cobos

Electronic Thesis and Dissertation Repository

Biocompatible titanium-alloys can be used to fabricate patient-specific medical components using additive manufacturing (AM). These novel components have the potential to improve clinical outcomes in various medical scenarios. However, AM introduces stability and repeatability concerns, which are potential roadblocks for its widespread use in the medical sector. Micro-CT imaging for non-destructive testing (NDT) is an effective solution for post-manufacturing quality control of these components. Unfortunately, current micro-CT NDT scanners require expensive infrastructure and hardware, which translates into prohibitively expensive routine NDT. Furthermore, the limited dynamic-range of these scanners can cause severe image artifacts that may compromise the diagnostic value of …

Targeting Prostate Cancer Through High Dose Rate Brachytherapy, Christopher Smith

Electronic Thesis and Dissertation Repository

While prostate cancer is not typically an aggressive disease, it can be lethal for some patients. Treatment of the disease has proven to be effective; however, when the disease recurs locally it does so most commonly at the site of the dominant intraprostatic lesion (DIL). An effective treatment method for prostate cancer is high dose rate brachytherapy (HDR-BT). This is a radiation therapy where a radioactive seed is interstitially inserted into the patient to deliver the radiation dose. It was the goal of this work to utilize preprocedural imaging and pathological data from radical prostatectomy specimens to investigate methods to …

Visualization And Manual Segmentation Of The Post-Mortem Human Amygdala Subnuclei Using Ultra High Field Magnetic Resonance Imaging, Sara M. Pac

Electronic Thesis and Dissertation Repository

The human amygdala is composed of 13 functionally and anatomically distinct subnuclei. Because most nuclei are difficult to distinguish at the microanatomical level, they are also challenging to discern macroscopically. In low field strength magnetic resonance imaging (MRI) studies, the amygdala can be identified only in its entirety. Higher resolution scans can be acquired by employing ultra-high field strength MRI acquisition techniques. We present a step-by-step guide for the manual segmentation of the amygdala subnuclei at ultra-high field 9.4T MRI. Post-mortem human brain specimen amygdala prosections fit for the 9.4T MRI bore allowed for the collection of high resolution T2-weighted …

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 …