A new approach using image analysis to assess pulmonary hypoplasia in the fetal lamb diaphragmatic hernia model
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In congenital diaphragmatic hernia (CDH), there is pulmonary hypoplasia (PH) and also pulmonary vascular and bronchial abnormalities. Few studies have investigated bronchial maldevelopment in CDH. We evaluated bronchial area (BA) by bronchography in a fetal lamb DH model to develop a measure of PH.
We created DH in fetal lambs at 75 days gestation, delivering by cesarean section and killing them at term (DH, n = 12). Normal term fetuses provided controls (C, n = 5). We measured total lung volume (TLV) and performed barium bronchography. Using image analysis, BA, total lung area (TLA) and bronchial area/lung area ratio (B/L ratio) were calculated. Student’s T test (p < 0.05; significant) and Spearman's correlation coefficient were performed.
TLV (ml) was 133.3 ± 41.2 in DH and 326 ± 22.5 in C (p = 0.0000001). TLA (cm2) was 78.8 ± 17.4 in DH and 107.1 ± 10.3 in C (p = 0.006). BA (cm2) was 39.6 ± 11.9 in DH and 52.2 ± 7.7 in C (p = 0.019). The B/L ratio was 0.45 ± 0.06 in DH and 0.49 ± 0.05 in C (p = 0.28). There are correlations in DH between TLV and TLA (r = 0.79), TLV and BA (r = 0.73) and in C between TLV and TLA (r = 0.97) and TLV and BA (r = 0.67).
It may be possible to assess PH on fetal MRI, given the correlation between TLV and TLA, and TLV and BA.
KeywordsCongenital diaphragmatic hernia CDH Pulmonary hypoplasia Image analysis Bronchial abnormalities
Management of the animals in the laboratory was supervised by Dr. Rebecca Dyson and Taylor Wilson, animal technicians at the BRU at University of Otago, Wellington. The ewes were bred by Mr. Denis Taylor, who also managed the flock on the farm between procedures. The authors thank Shigeko Ohnuma and the other staff in the Department of Pathology St. Marianna University School of Medicine for assistance in processing the histology.
This study was supported by the Japanese Society for Grant-in-aid of Scientific Research.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interest.
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