Medicine and Health Sciences Commons^™

Peptide-Mediated Targeting Of Angiogenesis For Molecular Imaging And Treatment Of Cancer, Choi-Fong Cho

Electronic Thesis and Dissertation Repository

The development of screening approaches to identify novel affinity ligands has paved the way for a new generation of molecular targeted nanomedicines. To identify novel targeting ligands, several studies have demonstrated the advantages in screening one-bead-one-compound (OBOC) libraries. Conventional methods typically bias the display of the target protein to ligands during the screening process. We have developed an unbiased multiplex ‘beads on a bead’ strategy to isolate, characterize, and validate high affinity ligands from OBOC libraries. In addition, due to the advantages associated with screening OBOC libraries directly against living cells, we sought to combine cell-based screen methods with automated …

Evidence Of Adult Lung Growth In Humans., Miranda Kirby, David G Mccormack, Grace Parraga

Medical Biophysics Publications

A 33-year-old woman underwent a right-sided pneumonectomy in 1995 for treatment of a lung adenocarcinoma. As expected, there was an abrupt decrease in her vital capacity, but unexpectedly, it increased during the subsequent 15 years. Serial computed tomographic (CT) scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Magnetic resonance imaging (MRI) with the use of hyperpolarized helium-3 gas showed overall acinar-airway dimensions that were consistent with an increase in the alveolar number rather than the enlargement of existing alveoli, but the alveoli in the growing lung were shallower than in normal lungs. This …

Hyperpolarized 3he And 129xe Mr Imaging In Healthy Volunteers And Patients With Chronic Obstructive Pulmonary Disease, Miranda Kirby, Sarah Svenningsen, Amir Owrangi, Andrew Wheatley, Adam Farag, Alexei Ouriadov, Giles E Santyr, Roya Etemad-Rezai, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography.

MATERIALS AND METHODS: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated …

What Can Computed Tomography And Magnetic Resonance Imaging Tell Us About Ventilation?, Brett A Simon, David W Kaczka, Alexander A Bankier, Grace Parraga

Medical Biophysics Publications

This review provides a summary of pulmonary functional imaging approaches for determining pulmonary ventilation, with a specific focus on multi-detector x-ray computed tomography and magnetic resonance imaging (MRI). We provide the important functional definitions of pulmonary ventilation typically used in medicine and physiology and discuss the fact that some of the imaging literature describes gas distribution abnormalities in pulmonary disease that may or may not be related to the physiological definition or clinical interpretation of ventilation. We also review the current state-of-the-field in terms of the key physiological questions yet unanswered related to ventilation and gas distribution in lung disease. …

Shift Work And Vascular Events: Systematic Review And Meta-Analysis., Manav V Vyas, Amit X Garg, Arthur V Iansavichus, John Costella, Allan Donner, Lars E Laugsand, Imre Janszky, Marko Mrkobrada, Grace Parraga, Daniel G Hackam

Medical Biophysics Publications

OBJECTIVE: To synthesise the association of shift work with major vascular events as reported in the literature.

DATA SOURCES: Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines.

STUDY SELECTION: Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population.

DATA EXTRACTION: Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, …

The Role Of Amino-Terminal In Determining Transjunctional Voltage-Dependent Gating And Unitary Conductance Of Cx36 And Cx50 Gap Junction Channels, Li Xin

Electronic Thesis and Dissertation Repository

Gap junction (GJ) channels directly connect the cytoplasm of neighboring cells, and allow for the transfer of ions and small molecules between two cells. GJ channels are known to be gated by the transjunctional voltage (V_j, the voltage difference between the interiors of adjoining cells), which is referred to as V_j-dependent gating. GJ channels show varying degrees of sensitivity to V_j, depending on the type of connexin(s) comprising the GJ channel. GJ channels formed by different connexins also show unique unitary conductance ranging from ~ 10 pS to ~300 pS. However, the molecular structures …

Mri-Based Attenuation Correction In Emission Computed Tomography, Harry R. Marshall

Electronic Thesis and Dissertation Repository

The hybridization of magnetic resonance imaging (MRI) with positron emission tomography (PET) or single photon emission computed tomography (SPECT) enables the collection of an assortment of biological data in spatial and temporal register. However, both PET and SPECT are subject to photon attenuation, a process that degrades image quality and precludes quantification. To correct for the effects of attenuation, the spatial distribution of linear attenuation coefficients (μ-coefficients) within and about the patient must be available. Unfortunately, extracting μ-coefficients from MRI is non-trivial. In this thesis, I explore the problem of MRI-based attenuation correction (AC) in emission tomography.

In particular, I …

Assessment Of Wear In Total Knee Arthroplasty Using Advanced Radiographic Techniques, Matthew G. Teeter

Electronic Thesis and Dissertation Repository

Total knee arthroplasty (TKA) has become the gold standard approach for treating advanced osteoarthritis of the knee. Although the surgery continues to be very successful at relieving pain and restoring joint function, its longevity is challenged by wear and loosening of the implant components. This requires the patient to undergo a revision surgery to replace the implant, a much more challenging operation than primary arthroplasty. Wear of the polyethylene tibial inserts from TKA is assessed in vitro using mechanical wear simulator testing and by examining failed implants retrieved from patients during revision surgery, as well as with direct in vivo …

Hearts And Minds: Examining The Evolution Of The Egyptian Excerebration And Evisceration Traditions Through The Impact Mummy Database, Andrew D. Wade

Electronic Thesis and Dissertation Repository

Egyptian mummification and funerary rituals were a transformative process, making the deceased a pure being; free of disease, injury, and disfigurements, as well as ethical and moral impurities. Consequently, the features of mummification available to specific categories of individuals hold social and ideological significance. This study refutes long-held classical stereotypes, particularly dogmatic class associations; demonstrates the apocryphal nature of universal heart retention; and expands on the purposes of excerebration and evisceration implied by synthetic and radiological analyses.

Features of the embalming traditions, specifically the variable excerebration and evisceration traditions, represented the Egyptian view of death. Fine-grain analyses, through primary imaging …

Modeling Oxygen Transport In Three-Dimensional Capillary Networks, Graham M. Fraser

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to examine how the use of real 3-dimensional (3D) capillary network geometries affect models of oxygen transport to tissue. Software was developed to reconstruct microvascular geometry in 3D from intravital video. Characterization of 3D reconstructions demonstrated that capillary density, length and capillary diameter were consistent with previous findings. Using reconstructed capillary networks a strategy was devised that utilized red blood cell (RBC) supply rate (SR) as a metric for flow modeling. Applying the RBC SR based flow model on baseline and perturbed flow conditions demonstrated that RBC SR is a major determinant of oxygen …

Quantitative Pulmonary Imaging Using Computed Tomography And Magnetic Resonance Imaging, George R Washko, Grace Parraga, Harvey O Coxson

Medical Biophysics Publications

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image-based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy …

Evaluating Bronchodilator Effects In Chronic Obstructive Pulmonary Disease Using Diffusion-Weighted Hyperpolarized Helium-3 Magnetic Resonance Imaging, Miranda Kirby, Mohammadreza Heydarian, Andrew Wheatley, David G Mccormack, Grace Parraga

Medical Biophysics Publications

The objective of this study was to evaluate the regional effects of bronchodilator administration in chronic obstructive pulmonary disease (COPD) using hyperpolarized helium-3 ((3)He) MRI apparent diffusion coefficient (ADC). Ten COPD ex-smokers provided written, informed consent and underwent diffusion-weighted, hyperpolarized (3)He MRI, spirometry, and plethysmography before and 25 ± 2 min after bronchodilator administration. Pre- and postsalbutamol whole-lung (WL) ADC maps were generated and registered together to identify the lung regions containing the (3)He signal at both time points, and mean ADC within those regions of interest (ROI) was determined for a measurement of previously ventilated ROI ADC (ADC(P)). Lung …

Medical Physics Staffing For Radiation Oncology: A Decade Of Experience In Ontario, Canada., Jerry J. Battista Dr., Brenda G Clark, Michael S Patterson, Luc Beaulieu, Michael B Sharpe, L John Schreiner, Miller S Macpherson, Jacob Van Dyk

Oncology Publications

The January 2010 articles in The New York Times generated intense focus on patient safety in radiation treatment, with physics staffing identified frequently as a critical factor for consistent quality assurance. The purpose of this work is to review our experience with medical physics staffing, and to propose a transparent and flexible staffing algorithm for general use. Guided by documented times required per routine procedure, we have developed a robust algorithm to estimate physics staffing needs according to center-specific workload for medical physicists and associated support staff, in a manner we believe is adaptable to an evolving radiotherapy practice. We …

Chest Mri In Children: Why Bother?, Amir M Owrangi, Grace Parraga

Medical Biophysics Publications

In this issue of Respirology, Montella and colleagues ask this question: How does high‐field chest MRI compare with CT of children with non‐cystic fibrosis (CF) lung disease? In an important extension of the first description of this study where they compared MRI and CT with pulmonary function measurements, the authors evaluated how widely‐used chest CT and almost never‐utilized lung MRI compare for diagnostic imaging of chronic lung disease. Here they show that high‐field (3Tesla as compared with the 1.5Tesla clinical standard) thoracic MRI has high reliability and good‐to‐excellent agreement with CT, definitively answering the important question at hand; their results …

Hyperpolarized 3he Functional Magnetic Resonance Imaging Of Bronchoscopic Airway Bypass In Chronic Obstructive Pulmonary Disease., Lindsay Mathew, Miranda Kirby, Donald Farquhar, Christopher Licskai, Giles Santyr, Roya Etemad-Rezai, Grace Parraga, David G Mccormack

Medical Biophysics Publications

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was

Modeling Stochastic And Spatial Heterogeneity In A Human Airway Tree To Determine Variation In Respiratory System Resistance, Del Leary, Swati A Bhatawadekar, Grace Parraga, Geoffrey N Maksym

Medical Biophysics Publications

Asthma is a variable disease with changes in symptoms and airway function over many time scales. Airway resistance (Raw) is variable and thought to reflect changes in airway smooth muscle activity, but just how variation throughout the airway tree and the influence of gas distribution abnormalities affect Raw is unclear. We used a multibranch airway lung model to evaluate variation in airway diameter size, the role of coherent regional variation, and the role of gas distribution abnormalities on mean Raw (Raw) and variation in Raw as described by the SD (SDRaw). We modified an anatomically correct airway tree, provided by …