title: Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD.
abstract: OBJECTIVE
  Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests.
  
  
  METHODS
  COPD patients (n=40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler(®) 320/9μg or formoterol Turbuhaler(®). OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function.
  
  
  RESULTS
  OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p<0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p<0.05) and increased oxygen extraction from the lung by 58% (p<0.01). Single-dose formoterol increased both lung wash-out time (+47%, p<0.05) and lung oxygenation time (+47%, p<0.05). FEV1 was improved by single-dose formoterol (+12%, p<0.001) and 8 weeks of budesonide/formoterol (+ 18%, p<0.001), consistent with published studies.
  
  
  CONCLUSIONS
  In COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.
authors.affiliation: Bioxydyn Ltd, Manchester, UK; Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK. Electronic address: alex.morgan@bioxydyn.com.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Morgan
authors.affiliation: Bioxydyn Ltd, Manchester, UK; Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Geoff J M
authors.initials: GJ
authors.lastname: Parker
authors.affiliation: Bioxydyn Ltd, Manchester, UK; Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Caleb
authors.initials: C
authors.lastname: Roberts
authors.affiliation: Bioxydyn Ltd, Manchester, UK.
authors.forename: Giovanni A
authors.initials: GA
authors.lastname: Buonaccorsi
authors.affiliation: Bioxydyn Ltd, Manchester, UK.
authors.forename: Niall C
authors.initials: NC
authors.lastname: Maguire
authors.affiliation: Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Penny L
authors.initials: PL
authors.lastname: Hubbard Cristinacce
authors.affiliation: University of Manchester, Medicines Evaluation Unit, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: University of Manchester, Medicines Evaluation Unit, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.affiliation: Department of Respiratory Medicine & Allergology, Skåne University Hospital, Lund, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.affiliation: Department of Clinical Physiology, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Jögi
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Taib
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Janeli
authors.initials: J
authors.lastname: Sarv
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Piet L B
authors.initials: PL
authors.lastname: Bruijnzeel
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Olsson
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Bondesson
authors.affiliation: Department of Respiratory Medicine & Allergology, Skåne University Hospital, Lund, Sweden; AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Nihlén
authors.affiliation: Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: McGrath
authors.affiliation: AstraZeneca R&D, Alderley Park, UK.
authors.forename: Simon S
authors.initials: SS
authors.lastname: Young
authors.affiliation: Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK; AstraZeneca R&D, Alderley Park, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Nordenmark
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D004338:Drug Combinations; D019819:Budesonide; D010100:Oxygen; D000068759:Formoterol Fumarate
keywords: Biomarkers; Chronic obstructive pulmonary disease; Dynamic; Lung function; Lung imaging; MRI