title: Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis.
abstract: BACKGROUND
  This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation.
  
  
  METHODS
  Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio).
  
  
  RESULTS
  Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively.
  
  
  CONCLUSIONS
  TVD responded to ivacaftor therapy.3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.
authors.affiliation: Department of Radiology, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA. Electronic address: altest@health.missouri.edu.
authors.forename: Talissa A
authors.initials: TA
authors.lastname: Altes
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: mac_johnson@vrtx.com.
authors.forename: Mac
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: meredith_fidler@vrtx.com.
authors.forename: Meredith
authors.initials: M
authors.lastname: Fidler
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: martynbotfield@gmail.com.
authors.forename: Martyn
authors.initials: M
authors.lastname: Botfield
authors.affiliation: University of Virginia, 480 Ray C. Hunt Drive, Snyder Building, Office 124, Charlottesville, VA 22903, USA. Electronic address: ntustison@gmail.com.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Tustison
authors.affiliation: University of Virginia, University Hospital, First Floor 1215 Lee St., Charlottesville, VA, 22908, USA. Electronic address: carlosleivasalinas@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Leiva-Salinas
authors.affiliation: University of Virginia, University Hospital, First Floor 1215 Lee St., Charlottesville, VA, 22908, USA. Electronic address: eed6s@virginia.edu.
authors.forename: Eduard E
authors.initials: EE
authors.lastname: de Lange
authors.affiliation: University of Virginia, 100 Hospital Dr #5408, Charlottesville, VA 22903, USA. Electronic address: dkf2x@virginia.edu.
authors.forename: Deborah
authors.initials: D
authors.lastname: Froh
authors.affiliation: University of Virginia, Snyder Translational Research Building - Room 154, 480 Ray C. Hunt Drive, Charlottesville, VA 22903, USA. Electronic address: jpm7r@virginia.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Mugler
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000008:administration & dosage*; D065101:Chloride Channel Agonists / Q000008:administration & dosage; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006371:Helium / Q000494:pharmacology; D006801:Humans; D007554:Isotopes / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D015363:Quinolones / Q000008:administration & dosage*; D016037:Single-Blind Method
chemical_list: D000627:Aminophenols; D065101:Chloride Channel Agonists; D007554:Isotopes; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D006371:Helium; C000615206:Helium-3
keywords: cystic fibrosis transmembrane conductance regulator modulator; forced expiratory volume; pulmonary