Characterization of reduced pulmonary arterial branching in rat with congenital diaphragmatic hernia: Automated quantitative imaging analysis

Abstract

Impaired fetal lung arterial histology determines degree of pulmonary hypertension in congenital diaphragmatic hernia (CDH). This study aims to demonstrate morphometric measurements differing in pulmonary arteries of fetuses with CDH. Age-matched 15 healthy and 5 Nitrofen-induced CDH SD rat fetuses at embryonic day 21 were included. Fetuses were scanned with micro-computed tomography. Pulmonary arterial tree9s 3D reconstruction was performed with artificial intelligence algorithms. Effective model for the vessel ordering schema of arterial trees was obtained via modified Strahler approach. Vessels with the smallest diameter are classified as order 1 (O1), order numbers increased with their diameters. Structural characteristics of the pulmonary vascular trees were compared with Mann-Whitney U and ANOSIM test. Number of segments in fetal CDH rat lungs was significantly lower than control on both left (U=2.5, p=0.004) and right (U=0, p=0.001) sides for O1, whereas there was significant difference only on right side for O2 and O3 (U=1, p=0.001, U=6, p=0.012), no differences for O4. Control group demonstrated that number of segments in right lung was higher than the ones in left lung only for O2 and O3 (U=13(p=0.003) and U=16.5(p=0.007), respectively). Pooled element numbers in control group obeyed Horton’s Law (R2=0.996 for left, and R2=0.811 for right lungs), while CDH group broke the law. Connectivity matrices showed that average number of elements of O1 springing from elements of O1 on the left side (U=5, p=0.014) and number of elements of O1 springing from elements of O3 on the right side (U=2.5, p=0.003) were significantly lower in CDH lungs. Herein, we demonstrated that radiological imaging techniques were able to define prenatal lung vascular tree.