title: Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema.
abstract: OBJECTIVE
  A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.
  
  
  METHODS
  Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.
  
  
  RESULTS
  PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.
  
  
  CONCLUSIONS
  The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction-before global changes occur.
authors.affiliation: Personalised Healthcare and Biomarkers, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zurek
authors.affiliation: Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Sladen
authors.affiliation: Personalised Healthcare and Biomarkers, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Edvin
authors.initials: E
authors.lastname: Johansson
authors.affiliation: Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Marita
authors.initials: M
authors.lastname: Olsson
authors.affiliation: Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Sonya
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
authors.forename: Gaell
authors.initials: G
authors.lastname: Mayer
authors.affiliation: Personalised Healthcare and Biomarkers, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.|MedTech West, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hockings
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests
chemical_list: D010196:Pancreatic Elastase; D010100:Oxygen