Medicine and Health Sciences Commons^™

The Vascular Link Between Intrauterine Hypoxia And Postnatal Cardiovascular Pathology, Jennifer A. Thompson

Electronic Thesis and Dissertation Repository

The effect of intrauterine hypoxia on arterial development was evaluated with use of large and small animal models. Analyses included expression and deposition of extracellular matrix (ECM) proteins, differentiation and proliferation of vascular smooth muscle cells (VSMCs), intima formation and wall thickening. A comprehensive investigation of possible molecular, mechanical and hormonal mediators of altered arterial development was afforded by a sheep model with both acute and chronic hypoxemia studies, whereas a guinea pig model allowed for long-term study. Our findings show that chronically hypoxic fetal sheep and intrauterine growth restricted (IUGR) guinea pigs exhibit a reduction in elastic fibre content …

Effects Of Methamphetamine On Sexual Behavior, Karla S. Frohmader

Electronic Thesis and Dissertation Repository

Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus (HIV). Currently, the neurobiological basis for this drug-sex nexus is unknown. Moreover, there is a lack of studies investigating the effects of Meth on sexual behavior and more importantly, compulsive sex-seeking behavior, under controlled experimental settings in animal models. First, using immuhistochemistry for mating- and Meth-induced neural activation it was demonstrated that Meth administration in male rats activates neurons in brain regions of the …

Magnetic Field Effects On The Neuroprocessing Of Pain, John A. Robertson

Electronic Thesis and Dissertation Repository

Magnetic fields can affect behaviour in a variety of ways, in a manner that is dependent on the particulars of the magnetic field exposure. A specific pulsed magnetic field with analgesic properties was investigated using functional magnetic resonance imaging with acute thermal pain. The functional activation of pain was significantly different pre/post exposure vs. a sham condition within areas of the brain associated with the affective component of pain, in particular the anterior cingulate and the right insula. Sleep was found to be a significant confound with a 45-minute exposure. This was the first time fMRI has been used as …

Decoding Motor Intentions From Human Brain Activity, Jason P. Gallivan

Electronic Thesis and Dissertation Repository

“You read my mind.” Although this simple everyday expression implies ‘knowledge or understanding’ of another’s thinking, true ‘mind-reading’ capabilities implicitly seem constrained to the domains of Hollywood and science-fiction. In the field of sensorimotor neuroscience, however, significant progress in this area has come from mapping characteristic changes in brain activity that occur prior to an action being initiated. For instance, invasive neural recordings in non-human primates have significantly increased our understanding of how highly cognitive and abstract processes like intentions and decisions are represented in the brain by showing that it is possible to decode or ‘predict’ upcoming sensorimotor …

Structural Role Of S100 Proteins In Membrane Repair, Atoosa Rezvanpour

Electronic Thesis and Dissertation Repository

Membrane repair can be modulated by the association of an S100A10 dimer with the calcium- and phospholipid-binding protein annexin A2. This heterotetrameric complex has the ability to form larger multiprotein assemblies such as those with the enlargeosome protein AHNAK and members of the transmembrane ferlin family. The main goals of this thesis were to design, synthesize and characterize a molecule that would facilitate assembly of larger S100 multiprotein complexes, investigate the arrangement of the proteins, stoichiometry and affinity of AHNAK for the S100A10-annexin A2 complex and identify structural details of the ternary complex formed between S100A10, annexin A2 and AHNAK. …

Real-Time Three-Dimensional Photoacoustic Imaging, Michael B. Roumeliotis

Electronic Thesis and Dissertation Repository

Photoacoustic imaging is a modality that combines the benefits of two prominent imaging techniques; the strong contrast inherent to optical imaging techniques with the enhanced penetration depth and resolution of ultrasound imaging. PA waves are generated by illuminating a light-absorbing object with a short laser pulse. The deposited energy causes a pressure change in the object and, consequently, an outwardly propagating acoustic wave. Images are produced by using characteristic optical information contained within the waves.

We have developed a 3D PA imaging system by using a staring, sparse array approach to produce real-time PA images. The technique employs the use …

In Vivo Cellular Mri In Experimental Traumatic Spinal Cord Injury, Laura E. Gonzalez-Lara

Electronic Thesis and Dissertation Repository

Spinal cord injury (SCI) remains one of the most devastating conditions in medicine; it is a complex medical condition with no cure currently available. Inflammation plays an important role in SCI as it can have both beneficial and detrimental effects. Cell therapy has emerged as a promising treatment for SCI due to the potential for stem cells, including multipotent mesenchymal stromal cells (MSC), for tissue regeneration and immunomodulation of the inflammatory cascade after the initial trauma. However, there are still important, unresolved questions regarding cell therapy that magnetic resonance imaging (MRI) can help to address by producing high-resolution images with …

Elucidating The Genetic Determinants Of The Archetypal Complex Disease Hypertriglyceridemia, Christopher T. Johansen

Electronic Thesis and Dissertation Repository

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Canada. Among non-traditional risk factors, plasma triglyceride (TG) concentration is re-emerging as a significant risk factor. Patients with hypertriglyceridemia (HTG) – an archetypal complex phenotype defined by fasting plasma TG concentration >95^th percentile – thus have significantly increased CVD risk, compounded by associated co-morbidities such as obesity, metabolic syndrome and type 2 diabetes. However, the molecular pathways contributing to HTG susceptibility are incompletely defined. A better understanding of the genetic determinants that underlie the phenotypic spectrum of plasma TG and HTG susceptibility is necessary to identify novel …

Representation Of Somatosensory Afferents In The Cortical Autonomic Network, Ruma Goswami

Electronic Thesis and Dissertation Repository

The relationship between somatosensory stimulation and the autonomic nervous system has been established with effects on heart rate (HR) and sympathetic tone. However, the involvement of the cortical autonomic network (CAN) during muscle sensory afferent stimulation has not been identified. The main objective of the research in this dissertation was to determine the representation of somatosensory afferents in the CAN and their physiologic impact on cardiovascular control. Somatosensory afferent activation was elicited by electrical stimulation of type I and II afferents (sub-motor threshold) and type III and IV afferents (motor threshold), and CAN patterns were assessed using blood-oxygenation level-dependent functional …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

Investigation Of Subchondral Bone Abnormalities Associated With Osteoarthritis Using Image-Based Biomechanics, David D. Mcerlain

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is degenerative disease caused by a mechanical failure of bone and cartilage. Common risk factors for developing OA include: being over-weight, female, having joint malalignment, or a history of prior joint injury. Post-traumatic OA is extremely common in the knee as individuals frequently suffer injuries to structures that provide stability to the joint. To enhance our understanding about OA, animal models are employed where the injury can be and monitored in a controlled environment. When used in conjunction with pre-clinical imaging techniques the longitudinal degradation of bone and cartilage can be quantitatively monitored in vivo. Recent evidence …

Predicting Drug Hypersensitivity Reactions: Mechanistic And Clinical Implications, Abdelbaset A. Elzagallaai

Electronic Thesis and Dissertation Repository

Adverse drug reactions (ADRs) are responsible for a high number of morbidities and mortalities worldwide and estimated to be the fourth most important cause of death in the US and Canada after heart diseases, cancer and stroke. ADRs are either type A (~80%) which are predictable, related to the drug pharmacology and dose-dependent or type B (~20%), which are unpredictable, unrelated to the drug pharmacology and have no clear dose-dependency. Drug hypersensitivity reactions (DHRs) represent the majority of type-B ADRs, which are rare but potentially fatal and unpredictable. The latter aspect makes DHRs very difficult to diagnose and necessitate the …

The Effects Of Low Protein During Gestation On Mouse Pancreas Development And Beta Cell Regeneration, Aaron R. Cox

Electronic Thesis and Dissertation Repository

Effects of a low protein (LP) diet during gestation on the metabolism of rat offspring have been well characterized and leads to glucose intolerance in adulthood. It is unknown how LP impacts endocrine pancreas development in the mouse, or whether this affects future β-cell plasticity. Streptozotocin (STZ) – induced β-cell injury has been demonstrated to be followed by β-cell regeneration in young animals, but the mechanism(s) of regeneration are not clear. Our objective was to characterize a mouse model of maternal LP, in addition to identifying factors that contribute to the long term development of glucose intolerance and the mechanism …

Modeling Lung Tissue Motions And Deformations: Applications In Tumor Ablative Procedures, Ali Sadeghi Naini

Electronic Thesis and Dissertation Repository

Various types of motion and deformation that the lung undergoes during minimally invasive tumor ablative procedures have been investigated and modeled in this dissertation. The lung frequently undergoes continuous large respiratory deformation, which can greatly affect the pre-planned outcome of the operation, hence deformation compensation becomes necessary. The first type of major deformation involved in a target lung throughout a tumor ablative procedure is the one encountered in procedures where the lung is totally deflated before starting the operation. A consequence of this deflation is that pre-operative images (acquired while the lung was partially inflated) become inaccurate for targeting the …

Mechanisms Of Atrial Arrhythmia: Investigations Of The Neuro-Myogenic Interface In The Mouse, Jari Michael Tuomi

Electronic Thesis and Dissertation Repository

Arrhythmia mechanisms rely on multiple factors including structural (myogenic), nervous (neurogenic), and interrelated (the neuro-myogenic interface) factors. I hypothesized that due to this neuro-myogenic interface, the intrinsic cardiac autonomic nervous system (ICANS) is involved in most atrial arrhythmias. This thesis also provides a "Threshold Model" as a tool to assess the role of different physiological factors influencing arrhythmia. This model allows relative comparison and interpretation of the role of various factors influencing arrhythmogenesis. The mouse allows relatively simple manipulation of genes to determine their role in arrhythmia. This thesis determined what atrial arrhythmias are inducible in the mouse (in vivo) …

Assessing And Improving 4d-Ct Imaging For Radiotherapy Applications, Greg Pierce

Electronic Thesis and Dissertation Repository

Lung cancer has both a high incidence and death rate. A contributing factor to these high rates comes from the difficulty of treating lung cancers due to the inherent mobility of the lung tissue and the tumour. 4D-CT imaging has been developed to image lung tumours as they move during respiration. Most 4D-CT imaging methods rely on data from an external respiratory surrogate to sort the images according to respiratory phase. However, it has been shown that respiratory surrogate 4D-CT methods can suffer from imaging artifacts that degrade the image quality of the 4D-CT volumes that are used to plan …

Glutamatergic Metabolites And Gray Matter Losses In Schizophrenia: A Longitudinal Study Using In Vivo Proton Magnetic Resonance Spectroscopy, Naoko Aoyama

Electronic Thesis and Dissertation Repository

Approximately one in hundred people suffer from schizophrenia. Current medications partially improve the symptoms. There is no cure. Glutamate, an excitatory neurotransmitter, is a possible cause of the schizophrenia symptoms. Excessive glutamate release eventually leads to neurodegeneration. Longitudinal studies are necessary to observe the neurodegenerative process.

Seventeen schizophrenia patients and 17 healthy volunteers underwent proton magnetic resonance spectroscopy (MRS) and imaging to measure neurochemical and structural changes in vivo. Metabolite levels were measured from a 1.5cm³ voxel in the anterior cingulate and thalamus using the stimulated echo acquisition mode sequence. Gray matter (GM) was assessed with voxel-based morphometry …

Fluid Percussion Injury In The Rat As An Animal Model Of Concussion: Cumulative Effects Of Repeated Concussion And Its Treatment By Anti-Cd11d Antibody, Sandy Rc Shultz

Electronic Thesis and Dissertation Repository

Traumatic brain injury is a global health concern with limited treatment options currently available. Concussion is the most common form of traumatic brain injury, and although a single concussion rarely results in long-term neurological dysfunction, repeated concussion can result in cumulative damage and chronic neurodegenerative disease. However, little is known about the factors and mechanisms of concussion involved in these detrimental effects. Animal models provide a means to examine the factors and mechanisms involved in traumatic brain injury, as well as potential treatments, in experiments that cannot be conducted using human participants. In the present thesis a fluid percussion model …

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …

Quantification Of Pulmonary Ventilation Using Hyperpolarized 3he Magnetic Resonance Imaging, Lindsay Mathew

Electronic Thesis and Dissertation Repository

Smoking-related lung diseases including chronic obstructive pulmonary disease (COPD) and lung cancer are projected to have claimed the lives of more than 30,000 Canadians in 2010. The poor prognosis and lack of new treatment options for lung diseases associated with smoking are largely due to the inadequacy of current techniques for evaluating lung function. Hyperpolarized ³He magnetic resonance imaging (MRI) is a relatively new technique, and quantitative measurements derived from these images, specifically the ventilation defect volume (VDV) and ventilation defect percent (VDP) have the potential to provide new sensitive measures of lung function. Here, we evaluate the reproducibility …

Hemodynamics In The Stenosed Carotid Bifurcation With Plaque Ulceration, Emily Y. Wong

Electronic Thesis and Dissertation Repository

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in …