Medicine and Health Sciences Commons^™

In Vivo Multi-Modal Imaging Approaches For Cancer, Stem And Immune Cells, Nourhan Shalaby

Electronic Thesis and Dissertation Repository

Introduction: Molecular imaging allows for non-invasive longitudinal visualization of cellular functions in vivo. This area of research has provided better understanding of fundamental molecular and biochemical processes, enabled optimization of pre-clinical and clinical assessments for new treatments, and allowed for more accurate and early detection of many pathologies. Extensive research for novel imaging techniques and emerging technologies have rapidly advanced the field. However, an ideal single imaging modality or approach does not exist. Alternatively, multi-modal imaging approaches are commonly applied to overcome limitations of individual technologies. In this thesis, we design, develop, validate, and image various cell types using …

Building A Magnetosome-Like Nanoparticle For Magnetic Resonance Imaging, Qin Sun

Electronic Thesis and Dissertation Repository

With its superb spatial and temporal resolution, magnetic resonance imaging (MRI) has great potential to track cellular activities that define early stages of disease. To improve molecular imaging techniques, we are developing MRI reporter gene expression based on the magnetosome. In magnetotactic bacteria (MTB), magnetosome formation compartmentalizes iron biominerals in membrane-enclosed vesicles. We hypothesize that essential magnetosome proteins interact in any cell type to form rudimentary magnetosome-like nanoparticles, providing a genetically-controlled contrast agent for molecular MRI.

MTB genes mamE, mamB, mamI, and mamL were cloned from M. magneticum sp. AMB-1 genomic DNA by PCR and inserted into …

Novel 129xe Magnetic Resonance Imaging And Spectroscopy Measurements Of Pulmonary Gas-Exchange, Alexander M. Matheson

Electronic Thesis and Dissertation Repository

Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy.

In vivo Xenon-129 gas-exchange magnetic resonance imaging (¹²⁹Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized ¹²⁹Xe gas, it …

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 …

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 …

Development Of A Computational Method For Assessing Static Field Induced Torque On Medical Implants, Xiao Fan Ding

Electronic Thesis and Dissertation Repository

The objective of this thesis is the development of a computational method for finding the torque induced on an object when placed in the static magnetic field of an MR scanner. As a preliminary step, the classic EM problems of a sphere and infinitely long cylinder of linear material was modeled in commercially available simulation software. Upon verification of the parameters implemented, the second step is the simulation of simple objects with realistic material properties, stainless-steel cylinders. Physical cylinders were machined to match those in the simulations and underwent the ASTM standard method for measuring induced torque. An adjacent study …

Texture Analysis And Machine Learning To Predict Pulmonary Ventilation From Thoracic Computed Tomography, Andrew Westcott

Electronic Thesis and Dissertation Repository

Chronic obstructive pulmonary disease (COPD) leads to persistent airflow limitation, causing a large burden to patients and the health care system. Thoracic CT provides an opportunity to observe the structural pathophysiology of COPD, whereas hyperpolarized gas MRI provides images of the consequential ventilation heterogeneity. However, hyperpolarized gas MRI is currently limited to research centres, due to the high cost of gas and polarization equipment. Therefore, I developed a pipeline using texture analysis and machine learning methods to create predicted ventilation maps based on non-contrast enhanced, single-volume thoracic CT. In a COPD cohort, predicted ventilation maps were qualitatively and quantitatively related …

Imaging Biomarkers Of Pulmonary Structure And Function, Dante Capaldi

Electronic Thesis and Dissertation Repository

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airflow limitations resulting from airway obstruction and/or tissue destruction. The diagnosis and monitoring of these pulmonary diseases is primarily performed using spirometry, specifically the forced expiratory volume in one second (FEV₁), which measures global airflow obstruction and provides no regional information of the different underlying disease pathologies. The limitations of spirometry and current therapies for lung disease patients have motivated the development of pulmonary imaging approaches, such as computed tomography (CT) and magnetic resonance imaging (MRI). Inhaled hyperpolarized noble gas MRI, specifically using helium-3 (³He) and …

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 …

Multi-Nuclear Magnetic Resonance Imaging Of Obstructive Lung Disease, Khadija Sheikh

Electronic Thesis and Dissertation Repository

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated …

Pulmonary Imaging To Better Understand Asthma, Sarah Svenningsen

Electronic Thesis and Dissertation Repository

Asthma is characterized using the spirometry measurement of the forced expiratory volume in one second (FEV₁). Simple and inexpensive, FEV₁ provides a global estimate of lung function but this metric cannot regionally identify airways responsible for airflow limitation, asthma symptoms or control. Work that brought about an understanding that airway abnormalities are heterogeneously distributed within the lung in asthma patients has motivated the development of pulmonary imaging approaches, such as hyperpolarized helium-3 (³He) and xenon-129 (¹²⁹Xe) magnetic resonance imaging (MRI). These methods provide a way to visualize and quantify lung regions accessed by …

Investigation Of Endogenous In-Vivo Sodium Concentration In Human Prostate Cancer Measured With 23na Magnetic Resonance Imaging, Justin C. Peterson

Electronic Thesis and Dissertation Repository

Prostate cancer (PCa) is the most common malignancy in men. Aggressive prostate tumours must be identified, differentiated from indolent tumours, and treated to ensure survival of the patient. Currently, clinicians use a combination of multi-parametric magnetic resonance imaging (mpMRI) contrasts to improve PCa detection. While these techniques provide very good spatial resolution, the specificity is often insufficient to unequivocally identify malignant lesions.

Utilizing specialized MRI hardware developed for sensitive in-vivo detection of sodium, this work has investigated differences in sodium concentration between healthy and malignant prostate tissue. Patients with biopsy-proven PCa underwent conventional mpMRI and sodium MRI followed by radical …

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

Electronic Thesis and Dissertation Repository

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, …

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in a …

Delta Relaxation Enhanced Magnetic Resonance - Development And Application Of A Field-Cycling Contrast Mechanism, Yonathan Araya

Electronic Thesis and Dissertation Repository

Delta relaxation enhanced magnetic resonance (dreMR) is a novel imaging method capable of producing contrast proportional only to the concentration of the bound form of the targetable contrast agent using a dynamic field-cycling technique. The characteristic high relaxivity magnetic field dependence of bound paramagnetic contrast agents enables suppression of tissue contrast from unbound agents and unenhanced tissue, thereby increasing probe specificity. The dreMR technique requires an auxiliary actively shielded field-shifting insert electromagnet to modulate the strength of the main clinical magnetic field as a function of time during the relaxation and evolution periods of a pulse sequence.

Ablavar (approved for …