Metabolic Correlates In Spinal Cord Compression Measured By Magnetic Resonance Spectroscopy In The Motor And Sensory Cortices, Sandy Goncalves

Electronic Thesis and Dissertation Repository

Surgical outcome for patients suffering from cervical myelopathy (CM) is unpredictable with varying motor and sensory symptom recovery. Previous in-vivo magnetic resonance spectroscopy (MRS) studies of patients surgically treated for CM have demonstrated decreased N-acetylaspartate (NAA)/creatine levels in the motor cortex indicating reduced neuronal function. The goal of this thesis was to determine whether absolute NAA changes in the motor and sensory cortices mirror the pattern of motor and sensory functional change observed in patients post surgical treatment.

MRS data were acquired on a 3.0 Tesla Siemens MRI along with clinical outcome measures at baseline, 6-weeks and 6-months post-surgery. …

Modulation Of The Cardiomyocyte Hypertrophic Responses To Endothelin-1 By Adipocytes, Suresh Chandra Bairwa

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Leptin and adiponectin are the adipokines that are shown to exert pro-hypertrophic and anti-hypertrophic effects respectively, in cardiomyocytes. We sought to determine the direct interaction between the adipocytes and cardiomyocytes during endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and determine the role of leptin and adiponectin.

The adipose tissue conditioned medium (ACM) inhibited the ET-1-induced hypertrophy in a concentration-dependent manner and this anti-hypertrophic effect was more potent or reversed in the presence of leptin receptor antagonist (LRA; 0.1 nM) or adiponectin receptor-1 antibody (ARA; 100 ng/mL), respectively. ACM from heart failure rats induced by coronary artery ligation or obese rats did not mitigate …

Mouse Models Of Intervertebral Disc Development, Degeneration And Mechanical Loading, Matthew R. Mccann

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Intervertebral disc (IVD) degeneration is a complex and multi-factorial process that is influenced by aging, genetic predispositions and environmental influences, such as altered mechanical loading. While recent studies have begun to characterize changes in the IVD associated with degeneration, the underlying etiology remains elusive. It is thought that the loss of notochord cells from the nucleus pulposus (NP) is one initiating factor contributing to the cascade of disc degeneration. However, questions remain about the function of notochord cells within the disc, including their capacity as tissue specific progenitor cells for the nucleus pulposus. We have demonstrated, with the use of …

The Relationship Of Plantar Sensation With Standing Balance And Gait Post-Stroke, Stephen Parsons

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Gait and balance dysfunction after stroke limit independence and quality of life. Numerous contributing factors have been investigated but the role of sensation deficits has received little attention. This thesis investigated the relationship between plantar cutaneous sensation and 1) standing balance, 2) gait, and 3) use of vision to compensate for sensory loss with a secondary analysis of data from individuals with subacute stroke. Associations between standing balance, gait and sensation were investigated with Spearman correlations. Individuals classified as impaired or intact sensation were compared on gait and standing balance measures. This thesis found plantar sensation is related to standing …

Regulation Of Crfr1 And 5-Ht2ar By Pdz Domain-Containing Proteins Sap97 And Psd-95, Henry A. Dunn

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Previous studies identified a crosstalk mechanism whereby CRFR1 sensitized 5-HT_2AR-mediated signaling via interactions with PDZ domain-containing proteins: a mechanism that may underlie stress-induced anxiety and depression. This prompted an investigation into uncovering which PDZ domain-containing proteins could regulate the crosstalk between these two receptors, and how they could be regulated individually. In the current studies, a subset of PDZ domain-containing proteins were identified that may interact with CRFR1 and 5-HT_2AR. The focus narrowed to two candidates previously implicated in psychiatric disease: SAP97 and PSD-95. We confirmed SAP97 and PSD-95 as interacting partners of CRFR1 in adult …

Pancreatic Beta Cell Plasticity And Involvement Of Insulin-Expressing Progenitor Cells, Christine A. Beamish

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Islet transplants have been successfully used as treatment for diabetes, but are limited by shortages of cadaveric insulin-producing β-cells. An alternate source may be the dedifferentiation, expansion, and subsequent redifferentiation of pancreatic islets or β-cells using in vitro techniques prior to transplant. Based on protocols which described the dedifferentiation of human islets to ductal-like cells, we hypothesized that neonatal mouse islets could be similarly dedifferentiated in vitro. Dedifferentiation techniques produced significant duct-like cells, but redifferentiation to insulin-expressing cells was limited. RIPCre;Z/AP+/+ mice were consequently utilized to lineage trace β-cell fate during culture by a human placental alkaline phosphatase (HPAP) reporter. …

Influence Of Polycaprolactone And Basic Fibroblast Growth Factor On Gingival Fibroblasts, Sarah Michelsons

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Guided tissue regeneration (GTR) to regenerate periodontal tissue involves placement of a cell-occlusive barrier membrane functionally excluding the gingiva and associated oral epithelium from the periodontal defect. Gingival connective tissue (CT) contains a rich vascular plexus and is a source of progenitor cells which could contribute to periodontal regeneration. We propose the use of a novel biodegradable and bioactive electrospun fibrous polycaprolactone (PCL) scaffold loaded with microspheres releasing basic fibroblast growth factor (bFGF) to promote gingival CT growth while maintaining a barrier to the oral epithelium. Scaffolds supported human gingival fibroblast proliferation and mesenchymal cell infiltration in a bFGF dose …

Acquisition And Reconstruction Techniques For Fat Quantification Using Magnetic Resonance Imaging, Abraam S. Soliman

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Quantifying the tissue fat concentration is important for several diseases in various organs including liver, heart, skeletal muscle and kidney. Uniquely, MRI can separate the signal from water and fat in-vivo, rendering it the most suitable imaging modality for non-invasive fat quantification. Chemical-shift-encoded MRI is commonly used for quantitative fat measurement due to its unique ability to generate a separate image for water and fat. The tissue fat concentration can be consequently estimated from the two images. However, several confounding factors can hinder the water/fat separation process, leading to incorrect estimation of fat concentration.

The inhomogeneities of the main …

The Effect Of Diffusive And Convective Sodium Balance During Hemodialysis On Interdialytic Weight Gain, Benjamin Thomson

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Patients with end stage renal disease (ESRD) often require hemodialysis treatments in which blood’s water and dissolved solutes undergo diffusion and convection by exposure to an extracorporeal membrane. The leading cause of death in this population is cardiovascular, and how hemodialysis is prescribed alters total sodium balance, a critical determinant of cardiovascular health. We performed retrospective and prospective analysis of data from patients in the Southwestern Ontario Regional Hemodialysis Program. An increased Dialysate sodium (Dial-Na+) to Pre-dialysis plasma sodium (Pre- Na+) concentration difference (DPNa+) leads to adverse clinical outcomes in hemodialysis patients. The post- to pre-dialysis plasma sodium difference (PPNa+) …

Towards Stem Cell Treatment For Duchenne Muscular Dystrophy-Related Cardiomyopathy, Bogdan A. Bondoc

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Duchenne muscular dystrophy (DMD) is a progressive muscular degenerative disease affecting 1 in 3,500 boys. Cardiomyopathy is observed in 95% of patients aged 18 and older, accounting for 30% of deaths. While innovative treatments have been employed to curb symptoms in skeletal muscle, few show success in the heart, and no cure for DMD exists. Recently, regenerative therapy using cardiac stem cells (CSCs) has shown very promising results, but efficacy in DMD remains undetermined. This dissertation sought to provide preliminary insight into the effects of murine Sca-1⁺ CSC therapy. Three-dimensional echocardiography was validated and used to gauge cardiomyopathy in …

A Pseudo Non-Cartesian Pulse Sequence For Hyperpolarized Xenon-129 Gas Mri Of Rodent Lungs At Low Magnetic Field Strength, Krzysztof Wawrzyn

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Background: Early diagnosis of radiation-induced lung injury (RILI) following radiation therapy is critical for prevention of permanent lung damage. Pulmonary imaging using magnetic resonance imaging (MRI) of the apparent diffusion coefficient (ADC) of hyperpolarized xenon (¹²⁹Xe) gas shows promise for early measurement of RILI.

Methods: An ultra-short echo time imaging sequence based on a pseudo-Cartesian k-space trajectory, known as Sectoral, is implemented at low magnetic field (0.07 T) for efficient use of the non-renewable magnetization of hyperpolarized ¹²⁹Xe gas. A pilot study was performed to demonstrate the feasibility of ADC mapping using the Sectoral sequence …

Regulation Of The High-Affinity Choline Transporter Activity And Trafficking In Alzheimer’S Disease-Related Pathological Conditions, Leah K. Cuddy

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Cholinergic neurons play a key role in cognitive processes through the action of the neurotransmitter acetylcholine (ACh). Dysfunction of these neurons occurs in several neurodegenerative disorders, including Alzheimer’s disease (AD). The high-affinity choline transporter CHT recycles choline back into synaptic terminals, which is the rate-limiting step to ACh production. CHT proteins traffic between the cell surface and subcellular organelles in a constitutive manner, which maintains plasma membrane transporter levels, thereby regulating CHT activity and maintaining cholinergic transmission. Pathological conditions associated with AD may alter CHT function in a manner that reduces choline uptake activity and impairs cholinergic neurotransmission. Thus, my …

Quantitative Mri Correlates Of Hippocampal And Neocortical Pathology In Intractable Temporal Lobe Epilepsy, Maged Goubran

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Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI …

Quantitative Analysis Of Relaxation Rate Dependence On Interecho Time In Maga-Expressing, Iron-Labeled Cells, Casey Yesol Lee

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Reporter gene-based methods of labeling cells with iron is an emerging method of providing magnetic resonance imaging (MRI) contrast for long-term cell tracking and monitoring of cellular activities. This thesis investigates 9.4 T NMR properties of mammalian cells over-expressing a magnetotactic bacterial putative iron transport gene, MagA, and the associated untransfected parental cells. Cells were cultured in medium alone or supplemented with 250 μM ferric nitrate. Using the Carr-Purcell-Meiboom-Gill sequence, the relationship between R2 and interecho time was analyzed for each of the cell types using a model based on water diffusion in weak magnetic field inhomogeneities (Jensen and Chandra, …

The Effect Of Fixation Plate Length On Spinal Instability Following Anterior Cervical Plate Fixation For The Repair Of In Vitro Flexion-Distraction Injuries, Abdulaziz J. Al-Kuwari

Electronic Thesis and Dissertation Repository

Abstract:

The Effect of Fixation Plate Length on Spinal Instability Following Anterior Cervical Plate Fixation for the Repair of in Vitro Flexion-Distraction Injuries

Introduction: Anterior cervical decompression and fusion with a plate (ACDFP) is a commonly performed treatment following a traumatic injury to the subaxial cervical spine. The purpose of the presented work was to determine the biomechanical effect of plate length on cervical spine kinematic stability following ACDFP stabilization for a simulated traumatic injury.

Methods: Eleven fresh-frozen cadaveric C5-C6 and C6-C7 motion segments were examined in this study. To assess kinematics, flexibility testing was performed on each specimen …

Three-Dimensional Photoacoustic Tomography System Design Analysis And Optimization, Philip Wong

Electronic Thesis and Dissertation Repository

Photoacoustic tomography (PAT) is an emerging imaging modality capable of mapping optical absorption in tissues. It is a hybrid technique that combines the high spatial resolution of ultrasound imaging with the high contrast of optical imaging, and has demonstrated much potential in biomedical applications. Conventional PAT systems employ raster scanning to capture a large number of projections, thus improving image reconstruction at the cost of temporal resolution. Arising from the desire for real-time 3D PA imaging, several groups have begun to design PAT systems with staring arrays, where image acquisition is only limited by the repetition rate of the laser. …

Cell Death Regulates Injury And Inflammation During Renal Allograft Transplantation, Arthur Lau

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Renal transplantation invariably results in tissue injury resulting from ischemia reperfusion injury (IRI), inflammation, drug toxicity, and rejection. Tubular epithelial cells (TEC) comprise the majority of renal parenchyma and are susceptible to cell death and injury during diverse forms of inflammation, which has direct and indirect effects on long term allograft function. Renal TEC have the unique ability to attenuate inflammation and alloimmune injury through the expression of various mediators of cell death and inflammatory molecules. Inhibition of cell death pathways in renal allografts may influence outcomes of alloimmune responses and graft survival. In this body of investigation, alteration of …

Investigation Of Sox9 Ablation On Neuroplasticity And Recovery After Ischemic Stroke, Bethany Robin Lenore Bass

Electronic Thesis and Dissertation Repository

Neuroplasticity is a key factor in post-stroke functional recovery. A chief inhibitor of post-stroke neuroplasticity is the expression of chondroitin sulfate proteoglycans (CSPGs). Recent research has shown that the transcription factor SOX9 is responsible for upregulating the expression of CSPGs in the injured central nervous system. Accordingly, CSPG levels are significantly lower in mice with the Sox9 gene conditionally knocked out. The purpose of this study was to determine how Sox9 ablation affects neuroplasticity and recovery after stroke. Behavioural test results revealed that Sox9 KO mice exhibited significantly improved functional recovery after stroke compared to controls. This correlated with increased …

Regulation Of Metabotropic Glutamate Receptor 5 Activity By Ca2+/Calmodulin-Dependent Protein Kinase Iiα, Fitore Raka

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The metabotropic glutamate receptor 5 (mGluR5) is a GPCR coupled to the heterotrimeric G protein Ga_q/11 and activates signaling pathways important for excitatory synaptic transmission. Emerging studies reveal that Amyloid b (Ab) acts as an extracellular scaffold for mGluR5. We have identified Ca²⁺/Calmodulin-dependent protein Kinase IIα (CAMKIIα) as an interacting protein of mGluR5. We hypothesize that CaMKIIα plays a role in mGluR5 signaling and Ab produces differential effects on the regulation of mGluR5 by CAMKIIα. We find that overexpression of CAMKIIα significantly impairs mGluR5-mediated ERK1/2 phosphorylation but does not effect inositol phosphate formation or Ca²⁺ release. …

The Antisaccade Task: Visual Distractors Elicit A Location-Independent Planning 'Cost', Jesse C. Desimone

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Prosaccades are rapid eye movements with direct stimulus and response relations and are designed to bring the fovea onto a target or area of interest. In contrast, antisaccades require the inhibition of a prosaccade and the evocation of a saccade to a target’s mirror-symmetrical location. Previous work has shown that a remote (i.e., midline, contralateral) – but not proximal (i.e., ipsilateral) – task-irrelevant distractor relative to a visual target delays prosaccade reaction times (RT) (i.e., remote distractor effect: RDE). To my knowledge, however, no work has examined whether antisaccade RTs are similarly influenced by a RDE. Accordingly, I sought to …

The Effects Of Rhamm On Cell Division, Cell Motility, And Tumorigenesis, Sallie Elhayek

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Overexpression of a RHAMM isoform (RHAMM^Δ163) transforms fibroblasts but the mechanisms underlying this oncogenic function are not well understood. RHAMM^Δ163 binds to the mitotic spindle and centrosomes via a C-terminal leucine zipper; these interactions are predicted to regulate genomic stability and cell polarity and proposed to account for the oncogenic function of RHAMM^Δ163. We hypothesized that RHAMM leucine zipper maintains mitotic spindle integrity and impacts directional cell migration through its interactions with microtubule and centrosome structures. The consequences of a mutated leucine zipper on cell division, cell motility, and tumorigenesis were assessed. Although mutant RHAMM …

Task-Switching In Oculomotor Control: Systematic Investigations Of The Unidirectional Prosaccade Switch-Cost, Jeffrey Weiler

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An antisaccade requires suppressing a stimulus-driven prosaccade (i.e., response suppression) and remapping a target’s spatial location to its mirror-symmetrical position (i.e., vector inversion). Notably, my previous work demonstrated that the successful execution of an antisaccade selectively lengthens the reaction time (RT) of a subsequently completed prosaccade (i.e., the unidirectional prosaccade switch-cost; Weiler & Heath, 2012a; Weiler & Heath, 2012b). Thus, the objective of this dissertation was further investigate, and ultimately provide a mechanistic explanation for the unidirectional prosaccade switch-cost.

In Chapter Two, I demonstrate that the magnitude of the unidirectional prosaccade switch-cost is not dependent of the number of …

Fully Automated Segmentation And Quantification Of Abdominal Adipose Tissue Compartments In Mouse Mri, Colin M. Mccurdy

Electronic Thesis and Dissertation Repository

Obesity currently affects 25% of Canadians and is strongly associated with many diseases including diabetes, cardiovascular disease, and cancer. However, only Intra-Abdominal Adipose Tissue (IAAT) is an important predictor of obesity associated disease and mortality. Magnetic Resonance Imaging (MRI) is an effective modality for imaging fat and methods have been developed to automate segmentation of IAAT. Currently existing techniques for automated segmentation in mice require acquisition using high magnetic field MRI equipment and use image acquisition techniques with low precision for fat quantification. We demonstrate a new fully automated technique for fat quantification in clinical strength mouse MRI through adaptation …

Dual Energy Imaging For Determining Urinary Calculi Composition: A Theoretical And Experimental Study With Computed Tomography, Stephanie Nykamp

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Urinary calculi is a common problem worldwide and is associated with substantial patient morbidity and healthcare costs. The choice of treatment is dependent on the composition of the stone. Currently that can only be determined once it has been removed which is too late to impact treatment decisions. Considerable investigation into the use of dual-energy CT (DECT) for determining stone composition has lead to mixed results. The varied results may be due to inherent sources of error and it is unclear whether the mixed results with DECT are due to CT artifacts or insufficient fundamental difference in the linear attenuation …

Efficacy Of Novel Antifouling/Antimicrobial Coatings For The Prevention Of Urinary Device Associated Infection And Encrustation, Thomas O. Tailly

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Device associated urinary tract infections are a very important healthcare issue. Despite best efforts in preventing and treating these infections, many patients and physicians are still confronted with this problem. Our research group is involved in testing and evaluating new stent coatings for the prevention of device associated infections and device encrustation. In the current project, we tested two new coating copolymers, both based on a long chain polymer backbone and mussel adhesive protein to this purpose in a rabbit and porcine model. The results demonstrate efficiency of one copolymer in preventing infections in the rabbit model. Interestingly there is …

Functional Imaging Of Malignant Gliomas With Ct Perfusion, Timothy Pok Chi Yeung

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The overall survival of patients with malignant gliomas remains dismal despite multimodality treatments. Computed tomography (CT) perfusion is a functional imaging tool for assessing tumour hemodynamics. The goals of this thesis are to 1) improve measurements of various CT perfusion parameters and 2) assess treatment outcomes in a rat glioma model and in patients with malignant gliomas. Chapter 2 addressed the effect of scan duration on the measurements of blood flow (BF), blood volume (BV), and permeability-surface area product (PS). Measurement errors of these parameters increased with shorter scan duration. A minimum scan duration of 90 s is recommended. Chapter …

Intensity Based Non-Rigid Registration Of 3d Whole Mouse Optical And Mr Image Volumes, Jacqueline Kathleen Harris

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Novel magnetic resonance (MR) imaging techniques can be validated using accurate co-registration with histology. Whole-animal histological sections allow for simultaneous analysis of multiple tissues, and may also aid in registration by providing contextual information and structural support to tissues which if isolated from the body would be difficult to register.

This thesis explores the feasibility of co-registration between whole mouse histology with 3D MR images using an intermediate optical image volume acquired during tissue sectioning. Of the two transformations required for this approach, 3D co-registration of MR and optical images is more challenging to perform due to changes in contrast, …

Transcriptional Regulation Of Peptidylarginine Deiminase Type Iv: Implications For Rheumatoid Arthritis, Ali Abbas

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High titers of anti-citrullinated protein antibodies have been detected in sera of rheumatoid arthritis (RA) patients, implicating citrullinating enzymes in the pathogenesis of RA. Peptidylarginine deiminase type IV (PAD4) is a member of the PAD family of enzymes that catalyze the post- translational modification of arginine to citrulline and has been linked with RA. However, little is known about its transcriptional regulation. Therefore, our aim was to determine how transcription of PAD4 is activated in the myeloid lineage. Using bioinformatics, a potential nuclear factor kappa B (NF-kB) binding site was identified on the PAD4 promoter. Luciferase assays were used to …

The Development Of A Digital X-Ray Imaging System For The Characterization Of Transmission Of Whole-Body Vibration In Mice, Zhengyi Hu

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Mechanical stimulus such as whole-body vibration (WBV) has shown to promote bone formation both in humans and animals. WBV has been hypothesized as a potentially useful osteoporosis intervention. While the transmission of WBV has been well characterized in humans, there is currently a lack of knowledge in the transmission of vibration in small animal models, such as mice, due to the lack of an implantable accelerometer appropriate to make such measurements. This thesis introduces an imaging-based method to quantify transmission of vibration in mice using x-ray imaging. Specifically, it utilizes motion blur of fiducial markers, which are implanted into the …

Magnetic Resonance Spectroscopy Investigations Of Alzheimer Disease, Jacob Penner

Electronic Thesis and Dissertation Repository

Alzheimer disease is a progressively devastating neurodegenerative disease of the brain that impairs cognition and is ultimately fatal. Cholinesterase inhibitors are the current standard treatment for Alzheimer disease and they can alleviate some of the symptoms and thus improve quality of life. Cognitive measures aid in the diagnosis and monitoring of individuals with Alzheimer disease, but they do not directly measure disease pathophysiology. The purpose of this thesis is to investigate metabolic changes measured with proton magnetic resonance spectroscopy within the hippocampus and posterior cingulate, two brain regions known to be effected in Alzheimer disease, following cholinesterase inhibitor treatment. Such …