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Structure And Function Of Asthma Evaluated Using Pulmonary Imaging, Rachel L. Eddy 2020 The University of Western Ontario

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) provides a ...


Characterization And Enhancement Of Local Drug Delivery In Orthopaedic Infection, Tina Khazaee 2020 The University of Western Ontario

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 ...


Role Of Atp1a1 In Skeletal Muscle Growth And Metabolism, Laura C. Kutz 2020 Marshall University

Role Of Atp1a1 In Skeletal Muscle Growth And Metabolism, Laura C. Kutz

Theses, Dissertations and Capstones

Skeletal muscle comprises approximately 30% of total body mass, and loss of muscle mass and dysfunctional muscle metabolism are implicated in multiple disease states, including type 2 diabetes, heart failure, and septic shock. As such, understanding the mechanisms of skeletal muscle growth and atrophy, including pharmaceutical targets that may prove safe and effective, is therefore an important goal of current research on skeletal muscle physiology. One potential target in skeletal muscle development and function that has not been fully explored is the Na/KATPase (NKA), especially the α1 isoform. This isoform has a unique signaling function that has previously been ...


Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell 2019 University of Arkansas, Fayetteville

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of ...


Normalisation Of Mri Ventilation Heterogeneity In Severe Asthma By Dupilumab, Sarah Svenningsen, Ehsan Ahmed Haider, Rachel L Eddy, Grace Parraga, Parameswaran Nair 2019 Western University

Normalisation Of Mri Ventilation Heterogeneity In Severe Asthma By Dupilumab, Sarah Svenningsen, Ehsan Ahmed Haider, Rachel L Eddy, Grace Parraga, Parameswaran Nair

Medical Biophysics Publications

Ventilation heterogeneity in asthma could be due to many reasons. Luminal obstruction due to inflammatory cells or mucus, smooth muscle constriction and airway wall thickness could all contribute individually or collectively to ventilation heterogeneity. Interleukin-4 and interleukin-13, acting through the common interleukin-4 receptor, have the potential to modulate all of these features of asthma.1 Inhaled hyperpolarised gas MRI provides a way to regionally visualise and quantify the functional consequence of these features.2 Dupilumab is a fully human monoclonal antibody directed against the alpha-subunit of the interleukin-4 receptor.3 Here, we report a severe asthmatic who showed significant improvement ...


Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G McCormack, Aaron D Ward, Aaron Fenster, Grace Parraga 2019 Western University

Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga

Medical Biophysics Publications

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (


Visualization Of The Small Airways:What It Is And Why It Matters, Mark L Schiebler, Grace Parraga 2019 Western University

Visualization Of The Small Airways:What It Is And Why It Matters, Mark L Schiebler, Grace Parraga

Medical Biophysics Publications

When the earth transitioned to an oxygen-containing atmosphere, many bacterial species were killed by the free radicals that developed in their cytoplasm. New life forms took advantage of this change by evolving to use oxygen as the final resting place for electrons involved in the Krebs cycle. Animals today rely on getting oxygen into the blood stream and getting carbon dioxide out by ventilation through sequentially smaller and smaller tubes until diffusion takes over, finally reaching the terminal respiratory bronchiole and its associated alveoli for gas exchange. All animals are obligate aerobes. One group has estimated that there are 274 ...


Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure, Juan Garcia Robledo M.D. 2019 The University of Western Ontario

Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure, Juan Garcia Robledo M.D.

Electronic Thesis and Dissertation Repository

Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and ...


Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong 2019 The University of Western Ontario

Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong

Electronic Thesis and Dissertation Repository

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this ...


Development Of A Computational Method For Assessing Static Field Induced Torque On Medical Implants, Xiao Fan Ding 2019 The University of Western Ontario

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 ...


Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon 2019 The University of Western Ontario

Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon

Electronic Thesis and Dissertation Repository

Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.

Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is ...


Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G McCormack, Grace Parraga 2019 Western University

Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition.

Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility

Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011 ...


Characterization Of A Non-Contact Imaging Scintillator-Based Dosimetry System For Total Skin Electron Therapy., Irwin I. Tendler, Petr Bruza, Michael Jermyn, Xu Cao, Benjamin B. Williams, Lesley A. Jarvis, Brian W. Pogue, David J. Gladstone 2019 Dartmouth College

Characterization Of A Non-Contact Imaging Scintillator-Based Dosimetry System For Total Skin Electron Therapy., Irwin I. Tendler, Petr Bruza, Michael Jermyn, Xu Cao, Benjamin B. Williams, Lesley A. Jarvis, Brian W. Pogue, David J. Gladstone

Open Dartmouth: Peer-reviewed articles by Dartmouth faculty

Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick  ×  15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied ...


An Apodized-Aperture X-Ray Detector Design For Improved Image Quality In Mammography, Tomi F. Nano 2019 The University of Western Ontario

An Apodized-Aperture X-Ray Detector Design For Improved Image Quality In Mammography, Tomi F. Nano

Electronic Thesis and Dissertation Repository

X-ray imaging for early cancer detection, such as screening mammography, requires images with high signal-to-noise ratio (SNR) using low levels of radiation exposure. Conventional detectors consist of a matrix of sensor elements, producing images where each pixel corresponds to a single sensor element. This imposes a fundamental limitation on image contrast and SNR for imaging fine detail for a given exposure. The work presented here reconsiders x-ray image formation using a new x-ray detector design that synthesizes image pixels from a large number of very small sensor elements with the goal of optimizing contrast and SNR.

Our new detector design ...


Scintillation Event Localization In Novel Hemi-Ellipsoid Detector For Spect, Hanif R. Soysal 2019 Louisiana State University and Agricultural and Mechanical College

Scintillation Event Localization In Novel Hemi-Ellipsoid Detector For Spect, Hanif R. Soysal

LSU Master's Theses

A high sensitivity Cardiac SPECT system using hemi-ellipsoid crystals with pinhole collimation was previously proposed by Dey et al. To investigate detector resolution for this design, the scintillation light spread on a monolithic hemi-ellipsoidal CsI crystal was simulated using Geant4 Monte Carlo. The expected distribution of scintillation light on the outer surface of the crystal from photoelectric absorption events was obtained from the simulations for selected points inside the crystal. Two sets of simulations were performed. For the first set, a look-up table (LUT) of 12 points was created and each point mapped to its expected light distribution—four points ...


Towards On-Line Plan Adaptation Of Unified Intensity-Modulated Arc Therapy Using A Fast-Direct Aperture Optimization Algorithm, Michael MacFarlane 2019 The University of Western Ontario

Towards On-Line Plan Adaptation Of Unified Intensity-Modulated Arc Therapy Using A Fast-Direct Aperture Optimization Algorithm, Michael Macfarlane

Electronic Thesis and Dissertation Repository

External beam radiotherapy (EBRT) plays a vital role in the treatment of cancer, with close to half of all cancer patients receiving EBRT at some point over their course of treatment. Although EBRT is a well-established form of treatment, there are a number of ways in which EBRT could still be improved in terms of quality and efficiency for treatment planning and radiation dose delivery. This thesis reports a series of improvements made to EBRT.

First, we developed and evaluated a new treatment planning technique called unified intensity-modulated arc therapy (UIMAT) which combines the optimization and delivery of rotational volumetric ...


Signal Intensity Analysis And Optimization For In Vivo Imaging Of Cherenkov And Excited Luminescence., Ethan P. M. LaRochelle, Jennifer R. Shell, Jason R. Gunn, Scott C. Davis, Brian W. Pogue 2019 Dartmouth College

Signal Intensity Analysis And Optimization For In Vivo Imaging Of Cherenkov And Excited Luminescence., Ethan P. M. Larochelle, Jennifer R. Shell, Jason R. Gunn, Scott C. Davis, Brian W. Pogue

Open Dartmouth: Peer-reviewed articles by Dartmouth faculty

During external beam radiotherapy (EBRT), in vivo Cherenkov optical emissions can be used as a dosimetry tool or to excite luminescence, termed Cherenkov-excited luminescence (CEL) with microsecond-level time-gated cameras. The goal of this work was to develop a complete theoretical foundation for the detectable signal strength, in order to provide guidance on optimization of the limits of detection and how to optimize near real time imaging. The key parameters affecting photon production, propagation and detection were considered and experimental validation with both tissue phantoms and a murine model are shown. Both the theoretical analysis and experimental data indicate that the ...


Texture Analysis And Machine Learning To Predict Pulmonary Ventilation From Thoracic Computed Tomography, Andrew Westcott 2019 The University of Western Ontario

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 ...


Evaluation Of Ventilation Assistance For Improving Respiratory Reproducibility In Radiation Therapy, Cameron J. Sprowls 2019 Louisiana State University and Agricultural and Mechanical College

Evaluation Of Ventilation Assistance For Improving Respiratory Reproducibility In Radiation Therapy, Cameron J. Sprowls

LSU Master's Theses

Background: Respiratory motion affects all tumor sites in the thorax and abdomen. Variations of the respiratory pattern cause variations of the tumor motion which can result in differences between the planned and delivered dose distributions. Previous breathing guidance techniques have been investigated to improve respiratory reproducibility; however, ventilation assistance has not been investigated. We evaluated using bi-level positive airway pressure (BIPAP) ventilation assistance for improving respiratory reproducibility in patients with tumor sites impacted by respiratory motion.

Methods: Written informed consent was obtained for 10 patients currently undergoing radiation therapy treatment. Patients participated in sessions over their course of treatment, which ...


The Effect Of Sepsis On Cerebral Microvascular Blood Flow, Laura Mawdsley, Mamadou Diop, Chris G. Ellis 2019 Western University

The Effect Of Sepsis On Cerebral Microvascular Blood Flow, Laura Mawdsley, Mamadou Diop, Chris G. Ellis

Western Research Forum

Background: Sepsis is a dysregulated host response to infection that affects 18 000 000 people worldwide, and over 325 000 000 dollars are spent treating sepsis in Canada every year. One of the symptoms of severe sepsis is an altered mental state, which is accompanied with a measured decrease in oxygen levels in the skeletal muscle microvasculature. It is hypothesized that his altered mental state is due to a lack of oxygenated blood reaching the brain.

Hypothesis: After the onset of sepsis, microvascular cerebral blood flow and oxygen levels in the blood will decrease. Onset of decreased blood flow in ...


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