Medicine and Health Sciences Commons^™

Investigating A Novel Receptor That Mediates Vasoconstriction In Mouse Femoral Arteries, Joselia Carlos

Electronic Thesis and Dissertation Repository

The synthetic peptide trans-cinnamoyl-leucine-isoleucine-glycine-arginine-leucine-ornithine-amide (tcLIGRLO) causes smooth muscle contraction in mouse femoral arteries. The identity of the receptor that mediates this response is undetermined. We hypothesize that the novel mechanism for tcLIGRLO-induced contractions involves a G-protein coupled receptor (GPCR) and a G_q-Ca²⁺ signalling pathway. Chapter 2 describes experiments using femoral arteries isolated from male and female systemic protease-activated receptor 2 (PAR2KO) mice (n=31; 21 – 39 weeks of age) using tcLIGRLO and the G_q-inhibitor, YM-254890 (YM). Contractions produced by tcLIGRLO did not differ by sex but decreased as age increased. YM inhibited tcLIGRLO-induced contractions. Chapter …

Investigating Bone Cement Susceptibility Related Artifacts And Adhesion, Eric Kuindersma

Electronic Thesis and Dissertation Repository

Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) utilizes pulse sequences sensitive to changes in concentration of deoxyhemoglobin to indirectly measure neural activity. Sequences used for BOLD are sensitive to magnetic susceptibility differences that may cause signal voids. Our lab has designed an awake marmoset head coil that eliminates confounds associated with imaging an animal under anesthesia. This design requires a head chamber attached to an animal’s skull with a cement that may cause a susceptibility artifact. Motivation behind this project was to find an MRI compatible cement that remains secure to the skull with minimal artifacts. Four …

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 …

Frequency Dependent Diffusion Kurtosis Measurement In The Human Brain With Oscillating Gradients, Kevin B. Borsos

Electronic Thesis and Dissertation Repository

Oscillating gradient spin-echo (OGSE) is an implementation of diffusion MRI that enables shorter effective diffusion times than the conventional pulse gradient spin-echo (PGSE) by periodically modulating the diffusion gradient. Measurements of the diffusion kurtosis, which reflects the degree of restricted diffusion, have previously been prohibited with OGSE due to technical limitations of clinical gradient systems. This thesis presents a novel oscillating gradient waveform that enables the measurement of kurtosis using OGSE without requiring advanced gradient hardware. Decreases of kurtosis are observed in OGSE acquisitions of healthy human subjects relative to PGSE, demonstrating the dependence of the kurtosis on oscillation frequency. …

Delineating The Skeletal Muscle-Microvessel Regeneration Program After Ischemic Injury, Jason J. Lee

Electronic Thesis and Dissertation Repository

Understanding the cellular processes involved in skeletal muscle regeneration after damage is critical to advancing translational efforts toward the development of targeted therapeutics. The purpose of this thesis was to ascertain the dynamic interplay between regenerating muscle and regenerating blood vessels after ischemic injury.

First, using a novel systematic investigation of a widely used preclinical mouse model of limb ischemia, I generated a detailed atlas of muscle injury zones and angiogenesis zones in C57BL/6 mice subjected to femoral artery excision. This uncovered previously unrecognized regional variability and an exclusive relationship between angiogenesis and actively regenerating muscle zones. Then, an unbiased, …

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 …

Three-Dimensional Ultrasound Imaging For Quantifying Knee Cartilage Volume, Samuel Papernick

Electronic Thesis and Dissertation Repository

Arthritis is the most common chronic health condition in Canada, with the most common form being osteoarthritis (OA). There is a great clinical need for an objective imaging-based point-of-care tool to assess OA status, progression, and response to treatment. This thesis aims to validate a handheld mechanical three-dimensional (3D) ultrasound (US) device against the current clinical standard of magnetic resonance imaging (MRI) for quantifying femoral articular cartilage (FAC) volume. Knee images of 25 healthy volunteers were acquired using 3D US and 3.0 Tesla MRI scans. Two raters manually segmented the trochlear FAC during separate sessions to assess intra- and inter-rater …

Computer-Assisted Lesion Classification And Intervention Planning For Prostate Cancer, Ryan M. Alfano

Electronic Thesis and Dissertation Repository

Multi-parametric magnetic resonance imaging (mp-MRI) is emerging as a useful tool for classifying prostate cancer (PCa); however, it suffers from two major limitations: (1) complex, multi-dimensional signals make interpretation challenging and (2) inter-observer variability of lesion classification between physicians. Critically needed are methods for augmenting the interpretability of mp-MRI to assist in lesion classification. To meet this need, we leveraged a patient cohort with post-surgery pathologist-annotated transverse histology images registered to pre-surgery in-vivo mp-MRI with a measured target registration error. We developed a radiomics-based machine learning model trained on annotations for PCa vs. non-PCa, and found that a 5-feature Naïve-Bayes …

In Vivo Detection Of Car-T Cell Immunotherapy Using 3 Tesla Fluorine-19 Mri, Veronica Dubois

Electronic Thesis and Dissertation Repository

Chimeric antigen receptor (CAR) T cell therapy is an emerging cancer treatment that has shown remarkable success in the treatment of B cell malignancies. However, this therapy still has the potential to cause severe toxicities or poor treatment responses in some patients. An imaging tool for tracking CAR-T cells could provide important patient-specific data on CAR-T cell fate. In chapter 2, fluorine-19 magnetic resonance imaging (¹⁹F MRI) was evaluated as a method to track the location of ¹⁹F perfluorocarbon (PFC) labeled CAR-T cells non-invasively in a mouse model of B cell leukemia. We show for the first …

Mri Of Structural & Functional Changes Associated With Western Diet Consumption, Lauren M. Smith

Electronic Thesis and Dissertation Repository

The Western diet (WD) is a high-fat, high-sugar diet increasingly common in the Western world and is associated with adverse effects in many organs, though the mechanisms behind these changes are unclear. Magnetic resonance imaging (MRI) techniques that provide structural and functional information non-invasively were used to investigate the effect of the WD on the liver and placenta in a guinea pig model.

The WD leads to a manifestation of the metabolic syndrome in the liver known as non-alcoholic fatty liver disease (NAFLD). Fat-fraction MRI was used to confirm the onset of NAFLD in a guinea pig model fed a …

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 …

Experimental, Theoretical, And Translational Studies Of Rbc Distribution In Capillary Networks, Asher Mendelson

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to evaluate the physiology of red blood cell (RBC) distribution in skeletal muscle capillary networks. Because this is the terminal site of oxygen exchange in the microcirculation, characterization of this fundamental process informs an understanding of how microvascular blood flow regulation matches oxygen supply with local tissue demand. Prior studies in this field have focused on small groups of capillaries, and have not linked capillary network structure with functional measurements, nor evaluated the temporal complexity of RBC distribution over physiologically-relevant scales. It is also unclear how the functional units called capillary modules – comprised …

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 …