Medical Biophysics Commons^™

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Mechanistic Basis For Atrial And Ventricular Arrhythmias Caused By Kcnq1 Mutations, Daniel C. Bartos

Theses and Dissertations--Physiology

Cardiac arrhythmias are caused by a disruption of the normal initiation or propagation of electrical impulses in the heart. Hundreds of mutations in genes encoding ion channels or ion channel regulatory proteins are linked to congenital arrhythmia syndromes that increase the risk for sudden cardiac death. This dissertation focuses on how mutations in a gene (KCNQ1) that encodes a voltage-gated K⁺ ion channel (Kv7.1) can disrupt proper channel function and lead to abnormal repolarization of atrial and ventricular cardiomyocytes.

In the heart, Kv7.1 coassembles with a regulatory protein to conduct the slowly activating delayed rectifier K^{+ …}

Raman Micro Spectroscopy For The Characterisation Of Cervical Cancer., Nosheen Rashid

Doctoral

The primary purpose of this study is to evaluate the potential of FTIR and Confocal Raman micro spectroscopy (CRM) in elucidating the biochemical changes occurring in different layers of the cervical epithelium including basal, superficial and the underlying connective tissue known as stroma during the progression of Cervical Intraepithelial Neoplasia (CIN) to cancer. Initially the two techniques were compared and Raman was chosen based on its higher spatial and spectral resolution. The sample preparation and spectral measurement procedures were optimised and all samples were formalin fixed paraffin processed, dewaxed using xylene, and measured on calcium fluoride windows. Raman spectra were …

Development Of A Beam-Specific Planning Target Volume And A Robust Plan Analysis To Ol For Proton Therapy, Peter Park

Dissertations and Theses (Open Access)

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of …

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 …

Neurophysiological Impact And Modeling-Independent Elucidation Of Inactivation Pathways In A-Type K+ Channels, J.D. Fineberg, David Ritter, Manuel Covarrubias

Department of Molecular Physiology and Biophysics Faculty Papers

Poster presented at Society for Neuroscience

Abstract:

A-type voltage-gated K⁺ channels auto-regulate their function by undergoing fast inactivation. Independent of molecular mechanisms, this inactivation can proceed after channel opening (open-state inactivation, OSI) or from a closed state prior to opening (closed-state inactivation, CSI). We hypothesize that the specific neurophysiological roles of A-type Kv channels depend on whether they undergo OSI, CSI or both (CSI+OSI). To explore these possibilities, we introduced Markov kinetic schemes of the A-type Kv4 conductance into a computational model of the hippocamcal CA1 neuron assuming either CSI or CSI+OSI and compared the properties of the somatic …

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, …

Male Breast Cancer, Edward Yu

Data and Test Instruments

No abstract provided.

Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui

Dissertations and Theses (Open Access)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In …

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 …

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 …

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 …

Optimal Strategy For Prophylactic Cranial Irradiation In Limited Stage Small Cell Lung Cancer, Edward Yu, Patricia Tai, Avi Assouline, Kurian Joseph

Data and Test Instruments

No abstract provided.

Glucose Decouples Intracellular Ca2+ Activity From Glucagon Secretion In Mouse Pancreatic Islet Alpha-Cells., Sylvain J Le Marchand, David W Piston

Farber Institute for Neuroscience Faculty Papers

The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+)](i)) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+)](i) and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP) channel activity but not on tetrodotoxin-sensitive Na(+) channels. …

Development And Implementation Of Acoustic Feedback Control For Scanning Probe Microscopy, Rodolfo Fernandez Rodriguez

Dissertations and Theses

A remote-sensing acoustic method for implementing position control feedback in Scanning Probe Microscopy (SPM) is presented. The capabilities of this feedback control using the new Whispering Gallery Acoustic Sensing (WGAS) method is demonstrated in a Shear-force Scanning Probe Microscope that uses a sharp probe attached to a piezoelectric Quartz Tuning Fork (QTF) firmly mounted on the microscope's frame. As the QTF is electrically driven its mechanical response reaches the SPM frame which then acts as a resonant cavity producing acoustic modes measured with an acoustic sensor strategically placed on the SPM head. The novelty of the WGAS resides in using …