Medicine and Health Sciences Commons^™

Hepcidin-Mediated Iron Regulation In P19 Cells Is Detectable By Mri, Kobra Alizadeh Pourbouyeh

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) can be used to track cellular activities in the body using iron-based contrast agents. However, intrinsic cellular iron handling mechanisms may also influence the detection of magnetic resonance (MR) contrast. For instance, inflammation involves downregulation of iron export in macrophages by the hormone hepcidin, due to degradation of the iron export protein, ferroportin (Fpn). We examined the effect of hepcidin on iron regulation and MR transverse relaxation rates in multi-potent P19 cells, which display high iron export activity, similar to macrophages. In response to varying conditions of iron supplementation, our results showed similar Fpn expression in …

Evaluating Small Airways Disease In Asthma And Copd Using The Forced Oscillation Technique And Magnetic Resonance Imaging, Heather M. Young

Electronic Thesis and Dissertation Repository

Obstructive lung disease, including asthma and chronic obstructive pulmonary disease (COPD), is characterized by heterogeneous ventilation. Unfortunately, the underlying structure-function relationships and the relationships between measurements of heterogeneity and patient quality-of-life in obstructive lung disease are not well understood. Hyperpolarized noble gas MRI is used to visualize and quantify ventilation distribution and the forced oscillation technique (FOT) applies a multi-frequency pressure oscillation at the mouth to measure respiratory impedance to airflow (including resistance and reactance). My objective was to use FOT, ventilation MRI and computational airway tree modeling to better understand ventilation heterogeneity in asthma and COPD. FOT-measured respiratory system …

A Longitudinal Study Of Tumour Metabolism Using Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging In A Preclinical Model Of Glioma, Heeseung Lim

Electronic Thesis and Dissertation Repository

Glioma is the most common and aggressive primary malignant brain tumour. Glioma is typically treated with surgery followed by radio/chemotherapy. Even with aggressive treatment, median survival time is expected to be ~12 to 15 months. Reoccurrence of glioma is almost inevitable, further threatening the well-being of patients who have already endured rigorous treatment. Therefore, it is paramount to choose the most effective therapy and to accurately determine outcome as early as possible to provide optimum end-of-life care. Tumours alter their metabolism in response to increasing energy demands, mainly through increased glycolysis and accompanying lactate production. This increases production of other …

Characterization Of An Orthotopic Rat Model Of Glioblastoma Using Multiparametric Magnetic Resonance Imaging And Bioluminescence Imaging, Trung Le

Electronic Thesis and Dissertation Repository

Glioblastoma multiforme (GBM) is a lethal and incurable disease. The C6 rat model of GBM shares several similarities to human GBM and longitudinal non-invasive imaging may allow tumour features to be studied. In this thesis, a multimodality imaging framework, consisting of bioluminescence imaging (BLI) and multiparametric magnetic resonance imaging (mpMRI), was applied to the C6 rat model to characterize the growth of orthotopic tumours. BLI signal, a measure of cell viability, tended to increase and then decrease in the majority of animals, whereas tumour volume (from MRI) continually increased. Cellular viability and tumour volume did not correlate across all days, …

Electrospun Collagen Nanofibers For Tissue Engineering, Nisha Sharma

Electronic Thesis and Dissertation Repository

Design and fabrication of the scaffold is an important part of the tissue engineering process. Nanofibrous scaffolds based on proteins are gaining increasing acceptance due to its structural similarity to the extracellular matrix. Making use of the electrospinning technique, rat tail collagen type I nanofibers were produced using a collagen in hexafluoroisopropanol (HFIP) solution. In addition to optimizing the electrospinning process parameters, the effect of humidity on fiber morphology and diameter was investigated for fiber size control for particular tissue engineering applications. A generalized humidity effect on polymer fiber diameter of the polymer solution electrospinning process was developed. The as …

Using Computed Tomography Perfusion To Evaluate The Blood-Brain-Barrier And Blood-Tumor-Barrier Response Following Focused Ultrasound Sonication With Microbubble Administration, Hassaan Ahmed

Electronic Thesis and Dissertation Repository

The blood-brain-barrier (BBB) is the single most limiting factor in the delivery of neurotherapeutics into the brain. Focused ultrasound sonication combined with intravenous microbubble administration (FUSwMB) is a novel technique that can transiently disrupt the BBB, with minimal vascular or tissue damage, allowing for localized drug delivery over the targeted region. The goals of this thesis are to: 1) use computed tomography (CT) perfusion to measure the permeability surface area product (PS) following USwMB in normal rabbits with an intact BBB, and 2) to evaluate the blood-tumor-barrier (BTB) PS response following FUSwMB in a C6 rat glioma model.

The Design, Fabrication, And Characterization Of Nanoparticle-Protein Interactions For Theranostic Applications, Wai Hei Tse

Electronic Thesis and Dissertation Repository

Theranostics, a combination of therapeutics and diagnostics, spans a spectrum of research areas to provide new opportunities in developing new healthcare technologies and medicine at affordable prices. Through employing a personalized medicine approach, biotechnology can be tailored to the needs of an individual. Applications of theranostics include drug delivery carriers capable of sustained drug release and targeted delivery, biosensors with high sensitivity and selectivity, and diagnostic relevant entities that can be incorporated into the former technologies. Nanotechnology provides a suitable foundation for theranostics to build upon due to material-based properties; magnetism, biocompatibility, and quantum effects to name a few. Purpose …

Angiogenesis And Neo-Microcirculatory Function In Diseased Tissue Revealed By Intravital Microscopy, Giovanni-Michele Arpino

Electronic Thesis and Dissertation Repository

Angiogenesis is the process of generating new blood microvessels. In adults, angiogenesis is fundamental to tumor biology and also to tissues rendered ischemic from vascular occlusion. Despite a promising appeal, strategies designed to simulate or otherwise modify the angiogenic process in adult tissues have yet to realize significant therapeutic potential. Importantly, understanding the structure and function of new microvascular networks formed in adult, diseased tissues is limited. In fact, it remains unknown if a new or regenerated microcirculation can effectively deliver oxygen to the tissue. The purpose of this thesis was to seek out novel determinants of functional angiogenesis and …

3d Ultrasound In The Management Of Post Hemorrhagic Ventricle Dilatation, Jessica Kishimoto

Electronic Thesis and Dissertation Repository

Enlargement of the cerebral ventricles is relatively common among extremely preterm neonates born before 28 weeks gestational age. One common cause of ventricle dilatation is post hemorrhagic ventricle dilatation following a bleed in the cerebral ventricles. While many neonates with PHVD will have spontaneous resolution of the condition, severe, persistent PHVD is associated with a greater risk of brain injury and morbidity later in life and left untreated can cause death. The current clinical management strategy consists of daily measurements of head circumference and qualitative interpretation of two-dimensional US images to detect ventricular enlargement and monitoring vital signs for indications …

In Vivo Magnetic Resonance Imaging Morphometry Measurements Of Pulmonary Airspace Enlargement, Eric J. Lessard

Electronic Thesis and Dissertation Repository

Diffusion-weighted magnetic resonance imaging (MRI) provides unparalleled information and measurements of lung structure and function without the burden of ionizing radiation. In particular, diffusion-weighted MRI provides estimates of airspace enlargement, which is a hallmark characteristic of emphysema. MRI provides a way to measure in vivo mean-linear-intercept (L_m) and this is a promising measurement for clinical evaluation of disease progression in patients with Alpha-1 Antitrypsin Deficiency (AATD) in which airspace enlargement begins early in life. As such, our objective was to evaluate MRI measurements of airspace enlargement in AATD patients and compare these measurements to ex-smokers with chronic obstructive …

Automated Vascular Smooth Muscle Segmentation, Reconstruction, Classification And Simulation On Whole-Slide Histology, Yiwen Xu

Electronic Thesis and Dissertation Repository

Histology of the microvasculature depicts detailed characteristics relevant to tissue perfusion. One important histologic feature is the smooth muscle component of the microvessel wall, which is responsible for controlling vessel caliber. Abnormalities can cause disease and organ failure, as seen in hypertensive retinopathy, diabetic ischemia, Alzheimer’s disease and improper cardiovascular development. However, assessments of smooth muscle cell content are conventionally performed on selected fields of view on 2D sections, which may lead to measurement bias. We have developed a software platform for automated (1) 3D vascular reconstruction, (2) detection and segmentation of muscularized microvessels, (3) classification of vascular subtypes, and …

Quantification Of Cerebral Blood Flow And Oxidative Metabolism In Infants With Post-Hemorrhagic Ventricular Dilatation, Peter Mclachlan

Electronic Thesis and Dissertation Repository

Post-hemorrhagic ventricular dilatation (PHVD) is highly predictive of mortality and morbidity among very low birth weight preterm infants. Impaired cerebral blood flow (CBF) due to elevated intracranial pressure (ICP) is believed to be a contributing factor. In this study, a hyperspectral near-infrared spectroscopy (NIRS) method of measuring CBF and the cerebral metabolic rate of oxygen (CMRO₂) was used to investigate perfusion and metabolism changes in patients receiving a ventricular tap (VT) based on clinical signs of elevated ICP. To improve measurement accuracy, the spectral analysis was modified to account for compression of the cortical mantle caused by PHVD …

Tools For Improving High-Dose-Rate Prostate Cancer Brachytherapy Using Three-Dimensional Ultrasound And Magnetic Resonance Imaging, William T. Hrinivich

Electronic Thesis and Dissertation Repository

High-dose-rate brachytherapy (HDR-BT) is an interstitial technique for the treatment of intermediate and high-risk localized prostate cancer that involves placement of a radiation source directly inside the prostate using needles. Dose-escalated whole-gland treatments have led to improvements in survival, and tumour-targeted treatments may offer future improvements in therapeutic ratio. The efficacy of tumour-targeted HDR-BT depends on imaging tools to enable accurate dose delivery to prostate sub-volumes. This thesis is focused on implementing ultrasound tools to improve HDR-BT needle localization accuracy and efficiency, and evaluating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for tumour localization.

First, we implemented a device enabling …

Developments In Pet-Mri For Radiotherapy Planning Applications, John Christian Patrick

Electronic Thesis and Dissertation Repository

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance …

Novel Determinants Of Smooth Muscle Cell-Based Vascular Integrity, Brittany N. Balint

Electronic Thesis and Dissertation Repository

Vascular smooth muscle cells (SMCs) impart stability to blood vessels, regulate vascular tone, and elaborate extracellular matrix (ECM). In healthy arteries, SMCs physically associate with one another in layered, circumferential arrangements and perform their functions in this context. However, there are circumstances in which SMCs lose their organization and their functionality. The purpose of this thesis was to identify new determinants of SMC-based vascular integrity.

Using a novel model of human SMC collectivization, I found that SMC-SMC adhesion entails the formation of adherens junction complexes consisting of cadherin-11 and N-cadherin hybrid nanotracks. These complexes formed rapidly and depended on withdrawal …