Semiquantitative measurement of murine bleomycin-induced lung fibrosis in in vivo and postmortem conditions using microcomputed tomography: correlation with pathologic scores--initial results.
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.
Lee
Hyun Ju
HJ
Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine. Seoul, Korea.
Goo
Jin Mo
JM
Kim
Na Ra
NR
Kim
Min A
MA
Chung
Doo Hyun
DH
Son
Kyu-Ri
KR
Kim
Hyo-Cheol
HC
Lee
Chang Hyun
CH
Park
Chang Min
CM
Chun
Eun Ju
EJ
Im
Jung-Gi
JG
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*
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin