Medicine and Health Sciences Commons^™

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

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 …

Oscillometry And Pulmonary Magnetic Resonance Imaging In Asthma And Copd, Rachel L Eddy, Andrew Westcott, Geoffrey N Maksym, Grace Parraga, Ronald J Dandurand

Medical Biophysics Publications

Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized

Hyperpolarized 3he Mri Ventilatory Apparent Diffusion Coefficient Of Alpha-1 Antitrypsin, Andrew Westcott, Dante P I Capaldi, Alexei Ouriadov, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Alpha-1 antitrypsin deficiency (AATD) leads to disabling chronic obstructive pulmonary disease (COPD). Current therapy aimed at slowing lung disease progression includes exogenous alpha-1 antitrypsin augmentation therapy, but there are few potential new treatments under development. Currently used measurements of AATD-related emphysema include the forced expiratory volume in 1 second (FEV1) and the diffusing capacity of carbon monoxide (DLCO); both are relatively insensitive to therapy, although computed tomography (CT) lung density measurements have been shown to worsen more slowly in treated patients.

Oscillometry And Pulmonary Mri Measurements Of Ventilation Heterogeneity In Obstructive Lung Disease: Relationship To Quality Of Life And Disease Control, Heather M Young, Fumin Guo, Rachel L Eddy, Geoffrey Maksym, Grace Parraga

Medical Biophysics Publications

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized

Mri Ventilation Abnormalities Predict Quality-Of-Life And Lung Function Changes In Mild-To-Moderate Copd: Longitudinal Tincan Study, Miranda Kirby, Rachel L Eddy, Damien Pike, Sarah Svenningsen, Harvey O Coxson, Don D Sin, David G Mccormack, Grace Parraga

Medical Biophysics Publications

CT biomarkers of emphysema (15th percentile of the CT density histogram, HU15%) and airways disease (wall thickness of airways with 10 mm internal perimeter, Pi10) have shown promise for providing prognostic information.2 Although recent data3 showed that the change in CT emphysema may be used to estimate the efficacy of therapy in patients with α-1-antitrypsin-deficiency, thus far none of the currently developed CT biomarkers have been shown to reflect changes in outcomes that are important to patients with COPD. MRI with inhaled noble gases provide highly sensitive and unique microstructural and functional information in COPD.4 MRI biomarkers of COPD are …

Pulmonary Ct And Mri Phenotypes That Help Explain Chronic Pulmonary Obstruction Disease Pathophysiology And Outcomes, Eric A Hoffman, David A Lynch, R Graham Barr, Edwin J R Van Beek, Grace Parraga

Medical Biophysics Publications

Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of …

This Is What Copd Looks Like, Khadija Sheikh, Harvey O Coxson, Grace Parraga

Medical Biophysics Publications

Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub-optimal COPD patient phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient-relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different …

Pulmonary Imaging Biomarkers Of Gas Trapping And Emphysema In Copd: (3)He Mr Imaging And Ct Parametric Response Maps, Dante P I Capaldi, Nanxi Zha, Fumin Guo, Damien Pike, David G Mccormack, Miranda Kirby, Grace Parraga

Medical Biophysics Publications

PURPOSE: To directly compare magnetic resonance (MR) imaging and computed tomography (CT) parametric response map (PRM) measurements of gas trapping and emphysema in ex-smokers both with and without chronic obstructive pulmonary disease (COPD).

MATERIALS AND METHODS: Participants provided written informed consent to a protocol that was approved by a local research ethics board and Health Canada and was compliant with the HIPAA (Institutional Review Board Reg. #00000940). The prospectively planned study was performed from March 2014 to December 2014 and included 58 ex-smokers (mean age, 73 years ± 9) with (n = 32; mean age, 74 years ± 7) and …

Copd: Do Imaging Measurements Of Emphysema And Airway Disease Explain Symptoms And Exercise Capacity?, Miranda Kirby, Damien Pike, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease.

MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and …

Pulmonary Ventilation Defects In Older Never-Smokers, Khadija Sheikh, Gregory A Paulin, Sarah Svenningsen, Miranda Kirby, Nigel A M Paterson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Hyperpolarized (3)He MRI previously revealed spatially persistent ventilation defects in healthy, older compared with healthy, younger never-smokers. To understand better the physiological consequences and potential relevance of (3)He MRI ventilation defects, we evaluated (3)He-MRI ventilation-defect percent (VDP) and the effect of deep inspiration (DI) and salbutamol on VDP in older never-smokers. To identify the potential determinants of ventilation defects in these subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise test (CPET) measurements, as well as occupational and second-hand smoke exposure. Fifty-two never-smokers (71 ± 6 yr) with no history of chronic respiratory disease were evaluated. During a single visit, …

On The Role Of Abnormal Dl(Co) In Ex-Smokers Without Airflow Limitation: Symptoms, Exercise Capacity And Hyperpolarised Helium-3 Mri, Miranda Kirby, Amir Owrangi, Sarah Svenningsen, Andrew Wheatley, Harvey O Coxson, Nigel A M Paterson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

BACKGROUND: The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood.

OBJECTIVE: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD.

METHODS: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and …

Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?, Damien Pike, Grace Parraga

Medical Biophysics Publications

No abstract provided.

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 …

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 …

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

Chronic Obstructive Pulmonary Disease: Quantification Of Bronchodilator Effects By Using Hyperpolarized ³He Mr Imaging, Miranda Kirby, Lindsay Mathew, Mohammadreza Heydarian, Roya Etemad-Rezai, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To evaluate short-acting bronchodilator effects in chronic obstructive pulmonary disease (COPD) by using hyperpolarized helium 3 (³He) magnetic resonance (MR) imaging, spirometry, and plethysmography.

MATERIALS AND METHODS: Fourteen ex-smokers with COPD provided written informed consent to a local ethics board-approved and Health Insurance and Portability Accountability Act-compliant protocol and underwent hyperpolarized ³He and hydrogen 1 MR imaging, spirometry, and plethysmography before and a mean of 25 minutes ± 2 (standard deviation) after administration of 400 μg salbutamol. Distribution of ³He gas was evaluated by using semiautomated segmentation of ³He voxel intensities, where cluster 1 represented regions of signal void …

Imaging Of Lung Function Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review Of Current And Emerging Translational Methods And Applications, Sean Fain, Mark L Schiebler, David G Mccormack, Grace Parraga

Medical Biophysics Publications

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical …

Hyperpolarized (3)He Magnetic Resonance Imaging-Derived Pulmonary Pressure-Volume Curves, Stephen Choy, Andrew Wheatley, David G Mccormack, Grace Parraga

Medical Biophysics Publications

We aimed to evaluate the potential for the use of hyperpolarized helium-3 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) surrogates of alveolar size, together with literature-based morphological parameters in a theoretical model of lung mechanics to simulate noninvasive transpulmonary pressure-volume curves. Fourteen ex-smokers with chronic obstructive pulmonary disease (COPD) (n = 8 stage II, n = 6 stage III/IV COPD) and five age-matched never-smokers, provided written, informed consent and were evaluated at baseline and 26 + or - 2 mo later (n = 15 subjects) using plethysmography, spirometry, and (3)He MRI at 3.0 T. Total lung capacity, residual volume, …

Chronic Obstructive Pulmonary Disease: Longitudinal Hyperpolarized (3)He Mr Imaging, Miranda Kirby, Lindsay Mathew, Andrew Wheatley, Giles E Santyr, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging.

MATERIALS AND METHODS: All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and …

Mapping And Quantifying Hyperpolarized 3he Magnetic Resonance Imaging Apparent Diffusion Coefficient Gradients, Andrea Evans, David G Mccormack, Giles Santyr, Grace Parraga

Medical Biophysics Publications

We measured hyperpolarized 3He magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) and quantified ADC gradients in each three-by-three voxel region of interest (ROI). Such local ADC gradients can be represented in vector maps showing the magnitude (|G3x3|) and direction of ADC gradients, providing a qualitative visualization tool and quantitative measurement of airway and air space heterogeneity. Twenty-four subjects (15 male, mean age=67+/-7 yr) with global initiative for chronic obstructive lung disease (GOLD) stage II (n=9, mean age 68+/-6 yr), GOLD stage III chronic obstructive pulmonary disease (COPD; n=7, mean age 67+/-8 yr), and age-matched healthy volunteers (n=8, mean age …