Detection And Quantification Of Cells Using Magnetic Particle Imaging And Magnetic Microspheres, Kierstin P. Melo

Electronic Thesis and Dissertation Repository

Magnetic particle imaging (MPI) is an emerging imaging modality that specifically detects superparamagnetic iron oxide nanoparticles (SPIOs). Our lab has shown that cell tracking with magnetic resonance imaging (MRI) has very high sensitivity, but low specificity and quantification of iron labeled cells is difficult. MPI cell tracking could overcome these limitations. A Momentum^TM MPI system was installed at Robarts in August 2019 and this is the first project to be completed using MPI. In Chapter 2 a series of in vitro experiments are reported which tested the repeatability and reproducibility of imaging SPIO labeled cell samples. There are no …

Improving Hydrid Pet/Mri Cardiovascular Imaging With Improved Hardware Design And Attenuation Correction Coefficient, Adam Helmy Farag

Electronic Thesis and Dissertation Repository

According to the World Health Organization (WHO) report in 2019, cardiovascular diseases (CVD) cause 52% of all illness-related deaths globally and are considered to be the second most common cause of death in Canada. CVD is also estimated to cost the Canadian economy about $21.2 billion in direct and indirect costs. With these figures, it is vital to develop the most effective and accurate methods and tools to diagnose accurately CVD and their causes. One of the promising tools for accurate diagnostic and therapeutic of CVD is the integrated Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) PET/MRI technology, …

Impact Of Graded Passive Cycling On Hemodynamics, Cerebral Blood Flow, And Heart Function In Healthy Adults And Septic Icu Patients, Jennifer Chen

Electronic Thesis and Dissertation Repository

Sepsis is a life-threatening dysregulation of host response to an infectious insult, which often leads to multi-organ failure. Sepsis survivors suffer from post-intensive care syndrome in part due to their prolonged bed rest and lack of mobility. Although early mobilization has been championed as a mechanism to counter the adverse effects associated with ICU immobility, due to sedation and mechanical ventilation, active early mobilization is not often administered in septic patients due to worries of hemodynamic instability and potential for inducing adverse events. Passive exercise is a mobilization modality that circumvents the need for patients to be conscious and participatory …

Chronic Neurological Impairment In Patients With Thrombotic Thrombocytopenic Purpura: Findings In Quantitative Mri, Jeffrey Hamilton

Electronic Thesis and Dissertation Repository

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, microvascular blood disorder that affects approximately 5 people per million per year. The disorder is characterized by insufficient activity in ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13), which is an important enzyme in hemostasis because it prevents thrombosis. Along with blood clotting, other predominant symptoms are fever, anaemia, kidney failure, and neurological changes. Neurological changes may include confusion and decreased levels of consciousness, as well as depression and increased risk of seizures or stroke. However, little is known about the general pathology of these neurological changes and this forms …

Metabolic Syndrome Impairs Cerebrovascular Tone And Behaviour In Obese Zucker Rats, Brayden D. Halvorson

Electronic Thesis and Dissertation Repository

Metabolic syndrome is associated with cerebrovascular disease and cognitive impairment. We determined vascular reactivity in middle cerebral arteries (MCA), and performed cognitive testing using an operant conditioning chamber (OCC) and Morris Water Maze (MWM). Male obese Zucker rats (OZR) were used to test the hypothesis that the pro-inflammatory environment present in the OZR impairs cerebrovascular tone regulation and is associated with neuroinflammation of the white matter and cognitive impairment. Dilation of MCA following challenge with acetylcholine was blunted, whereas constrictor responses were enhanced. Learning was impaired in the MWM and a shift in swim strategy towards increased allocentric navigation was …

The Development Of Bacterial Magnetic Resonance Imaging For Microbiota Analyses, Sarah C. Donnelly

Electronic Thesis and Dissertation Repository

Current microbial analyses to assess either the commensal microbiota or microorganism infection and disease typically require ex vivo techniques that risk contamination and are not undertaken in real time. The possibilities for employing imaging techniques in the microbiology field is becoming more prominent as studies expand on the use of positron emission tomography, ultrasound and numerous microscopy techniques. However, magnetic resonance imaging (MRI), a non-invasive in vivo modality that can produce real-time results is falling behind. Here, we examined the feasibility of detecting bacteria using clinical field strength MRI. Commensal, probiotic and uropathogenic Escherichia coli were scanned by 3 Tesla …

A 3d Microvessel Model For The Study Of Endothelial Cell Transluminal Pillar Formation, Emma Kate Prescott

Electronic Thesis and Dissertation Repository

BACKGROUND: Endothelial cells (ECs) line the blood vessel lumen and respond to fluid shear stress. ECs are also responsible for initiating the formation of new blood vessels. These new vessels can form either by sprouting angiogenesis or intussusceptive, or splitting, angiogenesis. The latter is poorly understood but recent evidence suggests that intussusception occurs with altered blood flow. However, the biomechanical and biochemical mechanisms of intussusceptive angiogenesis remain largely unknown and in vitro models do not exist.

The purpose of this thesis was to develop a three-dimensional EC culture model capable of forming transluminal pillars, a key step in angiogenesis, and …

Tspo Pet Detects Acute Neuroinflammation But Not Diffuse Chronically Activated Mhcii Microglia In The Rat, Nassir Al-Khishman

Electronic Thesis and Dissertation Repository

Abstract

Background

Accurate and sensitive imaging biomarkers are required to study the progression of white matter (WM) microglial activation in neurological diseases in vivo. The translocator protein (TSPO) is considered a sensitive target for imaging microglial activation with positron emission tomography (PET). This study aimed to test the ability of TSPO to detect WM microglial activation marked by major histocompatibility complex class II (MHCII) molecules in rat models of prodromal Alzheimer’s disease and acute subcortical stroke.

Methods

Fischer 344 wild-type (n = 12) and TgAPP21 (n = 11) rats were imaged with [¹⁸F]FEPPA PET and MRI to …

A Clinically Representative Rat Model Of Hip Hemiarthroplasty, Adam Dm Paish

Electronic Thesis and Dissertation Repository

Joint replacement is an increasingly common surgery with over 130,000 procedures performed annually in Canada. Although joint replacement surgery is highly successful, implants do not last a lifetime, and often have to be replaced via costly revision surgeries. Before innovations aimed at extending the life of implants are applied to the clinic, testing must be performed in animal models. Clinically representative small-animal models of joint replacement would be ideal in the initial stages of research and development, due to ease of handling and low costs, but few such models have been established in the literature. Thus, we describe the development …

A Hybrid Pet/Mri Brain Connectivity Approach For Improving Epilepsy Surgical Evaluation, Stefan E. Poirier

Electronic Thesis and Dissertation Repository

Hybrid PET/MRI can non-invasively improve epileptic focus (EF) localization prior to surgical resection in drug-resistant epilepsy (DRE), especially when MRI is negative. In this thesis, we developed an ¹⁸F-fluorodeoxyglucose (FDG) PET-guided diffusion tractography (PET/DTI) approach to assess white matter (WM) integrity in MRI-negative DRE and evaluated its potential impact on epilepsy surgical planning. To validate the potential of PET/MRI, we first evaluated the diagnostic competence of PET/MRI in DRE and found that PET/MRI provides similar diagnostic information as PET/CT (current clinical standard). For the PET/DTI approach, we used asymmetry index (AI) mapping of FDG-PET to guide WM fiber tractography …

Exploring The Effects Of Hemodialysis On Renal And Hepatic Blood Flow And Function Using Ct Perfusion Imaging, Raanan Marants

Electronic Thesis and Dissertation Repository

Hemodialysis (HD) is the most common form of renal replacement therapy for end-stage renal disease. However, patients develop complications that are driven by HD-induced circulatory stress from rapidly removing large fluid volumes during HD, making various vascular beds vulnerable to ischemia. By assessing how HD-induced circulatory stress affects different organs, it may be possible to characterize the mechanisms behind these complications and evaluate therapeutic interventions. This thesis aims to explore how HD affects renal and hepatic blood flow and function using CT perfusion imaging. For this work, patients received either standard or cooled HD first in a two-visit, crossover study …

Neurite Orientation Dispersion And Density Imaging In A Rodent Model Of Mild Traumatic Brain Injury, Patrick Mccunn

Electronic Thesis and Dissertation Repository

Mild traumatic brain injury (mTBI) has become a focal point within the medical community due to its increased prevalence in recent years. Unfortunately, there is currently no neuroimaging technique able to accurately diagnose and monitor mTBI in-vivo. One technique that has shown great promise is neurite orientation dispersion and density imaging (NODDI). NODDI is a diffusion MRI (dMRI) technique used to characterize microstructural complexity through the compartmental modelling of neural water fractions into Intra-neurite, Extra-neurite and CSF volume fractions. The overreaching theme of this thesis was to validate NODDI in a preclinical setting to then be applied to imaging …

Kinetic Analysis Of Dynamic Pet For Molecular, Functional And Physiological Characterization Of Diseases, Fiona Li

Electronic Thesis and Dissertation Repository

PET with targeted probes may better elucidate the molecular and functional basis of diseases. The widely used standardized uptake value from static imaging, however, cannot quantify the probe uptake processes like perfusion, permeability, binding to and disassociation (k₄) from target. The overarching thesis goal is to develop a model to enable kinetic analysis of dynamic imaging to separate these processes.

As perfusion delivery is not modelled in the current standard two tissue compartment (S2TC) model, I developed a flow modified two tissue compartment (F2TC) model that incorporates the blood flow effect. The model’s performances were investigated with simulation. …

Quantitative Dynamic Pet & Ct Perfusion For Cancer Imaging: Diagnosis & Monitoring Treatment Response, Dae-Myoung (Danny) Yang

Electronic Thesis and Dissertation Repository

Hybrid PET/CT imaging is a newer cancer imaging modality which allows contemporaneous PET metabolic/molecular and CT anatomical imaging during a single diagnostic session on a single device. However, current PET imaging has relied heavily on measuring the tracer accumulation in the tumour as a surrogate of the pathologic activity targeted by the tracer while CT is limited to measuring tumour size or visualizing tumour enhancement pattern, all of which lack sensitivity and specificity in detecting cancer and assessing treatment response. Therefore, it is critical to develop pharmacokinetic techniques for assessing the physiologic/molecular characteristics of tumours with clinical PET/CT scanners to …

A Novel System And Image Processing For Improving 3d Ultrasound-Guided Interventional Cancer Procedures, Derek J. Gillies

Electronic Thesis and Dissertation Repository

Image-guided medical interventions are diagnostic and therapeutic procedures that focus on minimizing surgical incisions for improving disease management and reducing patient burden relative to conventional techniques. Interventional approaches, such as biopsy, brachytherapy, and ablation procedures, have been used in the management of cancer for many anatomical regions, including the prostate and liver. Needles and needle-like tools are often used for achieving planned clinical outcomes, but the increased dependency on accurate targeting, guidance, and verification can limit the widespread adoption and clinical scope of these procedures. Image-guided interventions that incorporate 3D information intraoperatively have been shown to improve the accuracy and …

Structure And Function Of Asthma Evaluated Using Pulmonary Imaging, Rachel L. Eddy

Electronic Thesis and Dissertation Repository

Asthma has been understood to affect the airways in a spatially heterogeneous manner for over six decades. Computational models of the asthmatic lung have suggested that airway abnormalities are diffusely and randomly distributed throughout the lung, however these mechanisms have been challenging to measure in vivo using current clinical tools. Pulmonary structure and function are still clinically characterized by the forced expiratory volume in one-second (FEV₁) – a global measurement of airflow obstruction that is unable to capture the underlying regional heterogeneity that may be responsible for symptoms and disease worsening. In contrast, pulmonary magnetic resonance imaging (MRI) …

Machine Learning For Prostate Histopathology Assessment, Wenchao Han

Electronic Thesis and Dissertation Repository

Pathology reporting on radical prostatectomy (RP) specimens is essential to post-surgery patient care. However, current pathology interpretation of RP sections is typically qualitative and subject to intra- and inter-observer variability, which challenges quantitative and repeatable reporting of lesion grade, size, location, and spread. Therefore, we developed and validated a software platform that can automatically detect and grade cancerous regions on whole slide images (WSIs) of whole-mount RP sections to support quantitative and visual reporting. Our study used hæmatoxylin- and eosin-stained WSIs from 299 whole-mount RP sections from 71 patients, comprising 1.2 million 480μm×480μm regions-of-interest (ROIs) covering benign and cancerous tissues …

Characterization And Enhancement Of Local Drug Delivery In Orthopaedic Infection, Tina Khazaee

Electronic Thesis and Dissertation Repository

The delivery of antibiotics is an important component of therapy for orthopedic device-related infections (ODRI). In this study, we have investigated new techniques to characterize and enhance antibiotic delivery for ODRI. Characterization of small-molecule diffusion is essential to the development of drug-delivery systems. We have developed a quantitative, non-invasive, longitudinal, micro-CT technique to quantify the diffusion of small-molecules in an intact phantom. We employed a radio-opaque molecule (i.e., Iohexol) as a surrogate for commonly used antibiotics (e.g., Vancomycin). We characterized diffusion from a finite-core carrier into an agar, tissue-equivalent phantom. The estimate of the diffusion coefficient was derived …