Medical Biophysics Commons^™

Development Of Magnetic Particle Imaging For Quantitative Immune Cell Tracking, Julia J. Gevaert

Electronic Thesis and Dissertation Repository

The Foster lab has been developing cellular MRI tools for well over a decade using superparamagnetic iron oxide (SPIO)-based contrast agents for numerous applications cell tracking applications. SPIO are used to label cells which are indirectly detected as regions of signal loss. The main challenge with this technique is quantification of cell number, which is important for applications such as dendritic cell (DC)-based immunotherapies where cell number is used as a predictor of immunotherapeutic response.

Magnetic particle imaging (MPI) is a novel pre-clinical modality that shows promise for cell tracking. MPI directly detects the nonlinear magnetization response of superparamagnetic iron …

Spatiotemporal Optimization Of Intratumoural Electric Field Modulation For Cancer Therapy, Erin Iredale

Electronic Thesis and Dissertation Repository

The use of anti-cancer non-ablative electric fields is an expanding area of research that includes clinically available external devices for the treatment of glioblastoma (GBM), and a pre-clinical internal system called Intratumoural Modulation Therapy (IMT). IMT uses multiple electrodes implanted within the tumour to apply low intensity electric fields (~1 V/cm) focused on the target region, anywhere in the brain, with no externally visible devices. In this thesis, multi-electrode spatiotemporally dynamic IMT is investigated through computer simulation, numerical optimization, brain phantom and in vitro validation methods. These planning and validation strategies are hypothesized to improve tumour coverage with the necessary …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

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 …

Evaluating The Biomechanical, Functional, And Clinical Outcomes Of Bicruciate Stabilized Total Knee Arthroplasty, Jordan S. Broberg

Electronic Thesis and Dissertation Repository

Total knee arthroplasty (TKA) is the only solution for treating arthritis of the knee joint. Although it is successful at reducing pain and returning function to affected joints, one in five patients still report dissatisfaction following their operation. Bicruciate stabilized (BCS) TKA was developed to improve outcomes by replicating normal knee structure and function. The biomechanical, functional, and clinical outcomes for the BCS design were investigated in this thesis through radiographic imaging techniques, wearable sensor systems, and questionnaires in a cohort of TKA patients.

A stereo x-ray technique, called radiostereometric analysis (RSA), assesses implant fixation by tracking micromotion of TKA …

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 …

Longitudinal Computed Tomography Airway Measurements In Ex-Smokers With And Without Chronic Obstructive Pulmonary Disease, Paulina V. Wyszkiewicz

Electronic Thesis and Dissertation Repository

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic airflow obstruction, emphysematous destruction, and airway remodeling. Thoracic CT has previously revealed abnormalities in the small airways, where disease onset is believed to initiate. In previous COPD cohort studies, airway wall thinning and diminished total airway count (TAC) were observed with increasing disease severity. However, longitudinal insights are lacking. Accordingly, the objective of this thesis was to evaluate longitudinal CT airway measurements at baseline and after three-years in ex-smokers. I observed that CT TAC was decreased only in ex-smokers with COPD, whilst airway walls were thinner in both …

Exploring Novel Intradialytic Techniques To Identify & Ameliorate Of Hemodialysis-Induced Myocardial Ischemic Injury, Jarrin D. Penny

Electronic Thesis and Dissertation Repository

Patients with chronic kidney disease requiring hemodialysis to sustain life have extremely high rates of cardiovascular morbidity/mortality. This is both a consequence of the disease process and treatment. Hemodialysis induces systemic circulatory stress is largely due to the extracorporeal circuit and volume removal. The stress induced by intermitted hemodialysis is repetitive with cumulative cardiovascular effect and is the principal driver of heart failure and sudden death in this vulnerable population. The insults imposed by hemodialysis result in left ventricular regional wall motion abnormalities and lead to myocardial stunning with permanent damage to the vasculature and myocardium. Currently, the adversity caused …

The Characterization Of Hemodialysis Membranes In Miniaturized Dialyzers, Mehrshad Moradshahi

Electronic Thesis and Dissertation Repository

Lack of an appropriate animal model prevents rapid evaluation of health outcomes associated with hemodialysis. We developed a miniaturized dialyzer for use in small rats. The aim of this study was to investigate whether the miniaturized dialyzers can differentiate performance characteristics representing hemodialysis membrane and fiber design. We evaluated internal filtration, water permeability, sieving coefficient (SC) and clearance of solutes, in the Medium Cut Off (MCO) and conventional High Flux (HF) miniaturized dialyzers. We found statistically significant differences between miniaturized MCO and conventional HF dialyzers with respect to ultrafiltration coefficient, clearance of Beta-2 Microglobulin (B2M), and SC of B2M.These outcomes …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Estimation Of Free Water-Corrected Microscopic Fractional Anisotropy., Nico J J Arezza, Tales Santini, Mohammad Omer, Corey A Baron

Medical Biophysics Publications

Water diffusion anisotropy MRI is sensitive to microstructural changes in the brain that are hallmarks of various neurological conditions. However, conventional metrics like fractional anisotropy are confounded by neuron fiber orientation dispersion, and the relatively low resolution of diffusion-weighted MRI gives rise to significant free water partial volume effects in many brain regions that are adjacent to cerebrospinal fluid. Microscopic fractional anisotropy is a recent metric that can report water diffusion anisotropy independent of neuron fiber orientation dispersion but is still susceptible to free water contamination. In this paper, we present a free water elimination (FWE) technique to estimate microscopic …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Use Of Cardiomems Hf Sensor In Management Of Nyha Class Iii Heart Failure, Trevor Andrunik, Anne Eady

Physician Assistant Capstones, 2020-current

Objective: Assess the ability of continuous pulmonary artery pressure monitoring via implantable CardioMEMs HF device to reduce hospitalization in New York Heart Association (NYHA) Class III heart failure patients over the age of 18. Design: Systematic literature review. Methods: Searches were conducted via PubMed and ClinicalTrials.gov using the single search term “CardioMEMs.” Inclusion criteria narrowed results to studies performed in the last 10 years, randomized control trials, cohort studies, and utilizing heart failure related hospitalization as the primary endpoint. Results: The current data unanimously asserts that the CardioMEMs HF device is effective at reducing heart failure related hospitalizations, with secondary …

Simulated And Experimental Approaches To The Development Of Novel Test Phantoms For Radiofrequency Heating Of Implanted Medical Devices, Amgad M. Louka

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) has cemented itself as the gold standard for imaging of soft tissues and is only increasing in popularity. Given the rising number of MRI scanners and medical device being implanted into patients, it is becoming increasingly likely that patients undergoing MRI will have an implanted medical device (IMD). The presence of an elongated metallic IMD inside a scanner could result in dangerous interactions with the radiofrequency fields during MRI, thus some of these IMDs preclude the patients from being scanned.

Orthopedic devices typically fall into this category due to their high potential for RF induced heating, …

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V. Pappu, Tom Misteli

Department of Biochemistry and Molecular Biology Faculty Papers

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters …

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

Multi-Scale Computational Modeling Of Coronary Blood Flow: Application To Fractional Flow Reserve., Jermiah Joseph

Electronic Thesis and Dissertation Repository

Introduction. Fractional flow reserve (FFR) is presently an invasive coronary clinical index. Non-invasive CT imaging combined with computational coronary flow modelling may reduce the patient’s burden of undergoing invasive testing.

Research statement. The ability to obtain information of the hemodynamic significance of detected lesions would streamline decision making in escalation to invasive angiography.

Methods. A reduced order (lumped parameter) model of the coronary vasculature was further developed. The model was used in the assessment of the roles of structure and function on the FFR. Sophisticated methods were used to elicit numerical

solutions. Further, CT imaging (n = …

Anatomical And Functional Lung Imaging With Volumetric Computed Tomography In Non-Small Cell Lung Cancer, Heather Young

Electronic Thesis and Dissertation Repository

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. A significant challenge in treating NSCLC is balancing aggressive treatment with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges. 4-dimensional computed tomography (4D-CT) is an important part of motion management, but images often suffer from motion-induced artifacts. Volumetric CT scanners with wide axial field-of-view (aFOV) may reduce these artifacts and present an opportunity to advance CT-based functional lung imaging.

Chapter 2 presents a …

Atrial Fibrillation And Cognitive Decline: A Computational Hemodynamics Investigation, Timothy J. Hunter

Electronic Thesis and Dissertation Repository

Background: Atrial fibrillation (AF) is a prevalent cardiac disease which has been associated with increased risk of dementia and cognitive decline. We hypothesize that atrial fibrillation leads to regional transient hypoperfusion events in the brain, and that geometric variations in the arterial structure called the Circle of Willis (CoW) play a role in these events.

Methods: A computational model was developed to simulate cerebral blood flow in six common variations of the CoW. Risk was assessed based on frequency of beat-wise regional hypoperfusion events during AF, and sensitivity analysis was performed with respect to this model output.

Results …