New Technology to Assess Treatment for Chronic Obstructive Pulmonary Disease (COPD)
New Technology to Assess Treatment for Chronic Obstructive Pulmonary Disease (COPD)
First, the investigators will image patients with hyperpolarized xenon (Xe) magnetic
 resonance imaging (MRI) to develop the technique of hyperpolarized xenon MRI at the
 University of Virginia (UVA). Magnetic Resonance (MR) sequences will need to be developed and
 optimized for the equipment at UVA. These sequences will need to be evaluated in healthy
 adults for comparison with results obtained and in adults with lung diseases to optimize the
 sequences for the detection and evaluation of lung diseases. The MR pulse sequences need to
 be optimized for the parameters of a human MR coil and the gas exchange characteristics in
 healthy and diseased lungs.

 Second, the investigators propose to exploit the power of Xe129 MRI as a diagnostic tool to
 monitor therapeutic responses of a combination inhaler, Advair, which contains a long-acting
 beta-adrenoceptor agonist (LABA) and an inhaled corticosteroid (ICS) - two major classes of
 the current COPD therapeutics. The investigators will characterize the functional changes of
 the lungs with COPD at baseline, and investigate the responses of the lungs to the treatment
 after a three-month trial. Also the investigators will compare corresponding results obtained
 by Xe129 dissolved phase (DP) MRI to the results obtained by gadolinium-based dynamic
 contrast-enhanced perfusion MRI (perfusion MRI) and high resolution computed tomography
 (HRCT) of the lung to indirectly validate the Xe129 DP MRI technique. The investigators
 anticipate that the results from this project will greatly improve the investigators
 understanding of the lung functional responses of COPD subjects to current therapeutics.
 Also, the investigators expect that this project will provide evidence to consider Xe129 MRI
 as a diagnostic strategy to assess and monitor therapeutic responses of existing and new
 pharmaceuticals, and thus Xe129 MRI will stimulate development of novel therapies for COPD in
 the future
Inclusion Criteria:

 -  Subjects should be at their clinical baseline on the day of imaging

 -  Subjects must be clinically stable in order to participate in the study

 -  Smoking history >10 pack years

 -  Subjects must not be currently taking Advair or have taken it within 4 weeks prior to
 screening

 -  No subject will be withdrawn from Advair to participate in this study

 The subjects with COPD will be categorized according to the Global Initiative for Chronic
 Obstructive Lung Disease (GOLD) COPD severity classification:

 -  Class 1: forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) <
 70 and FEV1 > 80% predicted;

 -  Class 2: FEV1/FVC < 70 and 50% < FEV1 < 80% predicted;

 -  Class 3: FEV1/FVC < 70 and 30% < FEV1 < 50% predicted;

 -  Class 4: FEV1/FVC < 70 and FEV1 < 30% predicted

 Exclusion Criteria:

 -  Continuous oxygen use at home

 -  Blood oxygen saturation of 92% less than as measured by pulse oximetry on the day of
 imaging

 -  FEV1 percent predicted less than 25%

 -  Pregnancy or lactation

 -  Claustrophobia, inner ear implants, aneurysm or other surgical clips, metal foreign
 bodies in eye, pacemaker or other contraindication to MR scanning

 -  Subjects with any implanted device that cannot be verified as MRI compliant will be
 excluded.

 -  Chest circumference greater than that of the xenon MR and/or helium coil. The
 circumference of the coil is approximately 42 inches.

 -  History of congenital cardiac disease, chronic renal failure, or cirrhosis.

 -  Inability to understand simple instructions or to hold still for approximately 10
 seconds.

 -  History of respiratory infection within 2 weeks prior to the MR scan

 -  History of myocardial infarction (MI) , stroke and/or poorly controlled hypertension.

 -  Known hypersensitivity to albuterol or any of its components, or levalbuterol

 -  Glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 or known hypersensitivity to
 Gd-contrast agents based on a serum creatinine drawn within 30 days of the MRI

 -  Acute kidney injury

 -  History of paraproteinemia syndromes such as multiple myeloma

 -  Hepatorenal syndrome

 -  Liver transplant