title: Semiquantitative measurement of murine bleomycin-induced lung fibrosis in in vivo and postmortem conditions using microcomputed tomography: correlation with pathologic scores--initial results.
abstract: OBJECTIVE
  To evaluate whether the semiquantification of lung inflammation and fibrosis in murine bleomycin-induced lung fibrosis using micro-computed tomography (micro-CT) in in vivo and postmortem conditions is feasible, and to correlate micro-CT and pathologic scores.
  
  
  METHODS
  Bleomycin-induced lung fibrosis was created by intratracheally instilling 3 mg/kg of bleomycin into C57BL/6 mice. Mice were allocated randomly to 2-week, 4-week, and 8-week follow-up groups. In each group, in vivo and follow-up postmortem micro-CT were performed using a voxel size of 35 x 35 x 35 microm. Ground-glass opacity (GGO), consolidation, parenchymal lines, honeycombing, and peripheral bronchial dilatation were scored on micro-CT images in a semiquantitative fashion, whereas inflammation and fibrosis were scored histopathologically. The confidence levels of micro-CT findings were also scored. Correlations between micro-CT and pathologic findings were examined using Spearman rank correlation analysis, and differences between CT scores and confidence levels for in vivo and postmortem micro-CT were subjected to Wilcoxon signed rank testing. Agreements between in vivo and postmortem micro-CT scores were tested using weighted kappa statistics.
  
  
  RESULTS
  Consolidation in vivo (r = 0.46) and at postmortem (r = 0.39) and GGO in vivo (r = 0.31) by micro-CT showed fair to moderate correlation with pathologic inflammation scores (P < 0.001). By in vivo and postmortem micro-CT, parenchymal lines (r = 0.72 vs. 0.83) showed good to excellent and peripheral bronchial dilatation (r = 0.47 vs. 0.68) showed moderate to good correlation with pathologic fibrosis scores (P < 0.001). For GGO, consolidation, peripheral bronchial dilatation, and parenchymal lines, fair to moderate agreement was obtained between in vivo and postmortem micro-CT. However, confidence levels for peripheral bronchial dilatation, parenchymal lines, and honeycombing were significantly higher by postmortem micro-CT (P < 0.001).
  
  
  CONCLUSIONS
  Micro-CT scores and pathologic scores were found to be well correlated by in vivo and postmortem micro-CT. Although agreements between in vivo and postmortem micro-CT were significant, the confidence levels for fibrosis-related CT findings were significantly higher by postmortem micro-CT.
authors.affiliation: Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine. Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Goo
authors.forename: Na Ra
authors.initials: NR
authors.lastname: Kim
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Kyu-Ri
authors.initials: KR
authors.lastname: Son
authors.forename: Hyo-Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Park
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Chun
authors.forename: Jung-Gi
authors.initials: JG
authors.lastname: Im
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008838:Microcomputers; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D011897:Random Allocation; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin