title: 18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.
abstract: PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion.
  
  
  METHODS
  Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H2O; plateau pressure, 30 cm H2O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS+] group; n = 6) or not (lipopolysaccharide-negative group; n = 6). (18)F-FDG PET emission scans were then acquired. (18)F-FDG phosphorylation rate and distribution volume were calculated with a 4-compartment model. Lung tissue expression of inflammatory cytokines was measured using real-time quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  (18)F-FDG uptake increased in LPS+ (P = 0.012) and in surfactant-depleted sheep (P < 0.001). These increases were topographically heterogeneous, predominantly in dependent lung regions, and without interaction between alveolar lavage and LPS. The increase of (18)F-FDG uptake in the LPS+ group was related both to increases in the (18)F-FDG phosphorylation rate (P < 0.05) and to distribution volume (P < 0.01). (18)F-FDG distribution volume increased with infiltrating neutrophils (P < 0.001) and phosphorylation rate with the regional expression of IL-1β (P = 0.026), IL-8 (P = 0.011), and IL-10 (P = 0.023).
  
  
  CONCLUSIONS
  Noninvasive (18)F-FDG PET-derived parameters represent histologic and gene expression markers of early lung injury. Pulmonary metabolism assessed with (18)F-FDG PET depends on the mechanism of injury and appears to be additive for endotoxemia and surfactant depletion. (18)F-FDG PET may be a valuable imaging biomarker of early lung injury.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Medical Intensive Care Unit, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France nicolas.de-prost@hmn.aphp.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Prost
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Tyler
authors.initials: T
authors.lastname: Wellman
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Pulmonary Division, Cardio-pulmonary Department, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil; and.
authors.forename: Mauro R
authors.initials: MR
authors.lastname: Tucci
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Pulmonary Division, Cardio-pulmonary Department, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil; and.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Costa
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Guido
authors.initials: G
authors.lastname: Musch
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.affiliation: Department of Medicine (Pulmonary and Critical Care Unit), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Harris
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Venegas
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Vidal Melo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D005786:Gene Expression Regulation; D007249:Inflammation; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D011654:Pulmonary Edema / Q000000981:diagnostic imaging; D019275:Radiopharmaceuticals; D012128:Respiratory Distress Syndrome / Q000000981:diagnostic imaging*; D012756:Sheep; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D019275:Radiopharmaceuticals; D013501:Surface-Active Agents; D019788:Fluorodeoxyglucose F18
keywords: endotoxemia; fluorodeoxyglucose F18; positron emission tomography; pulmonary edema; respiratory distress syndrome, adult