The Fetal Lamb Model of Congenital Diaphragmatic Hernia Shows Increased Lung Stiffness Using Shear Wave Elastography

Purpose: Children born with congenital diaphragmatic hernia (CDH) have intrinsic lower lung compliance. Shear wave elastography (SWE) is an emerging, noninvasive tool to evaluate lung stiffness with the potential to predict postnatal lung function. SWE of the lung in CDH has never been performed in utero. We aimed to evaluate lung elastography in a fetal lamb model of CDH.

Methods: Following IACUC-approved protocols, 3 fetal lambs underwent left-sided CDH creation at 70-78 days gestational age (GA). 3 healthy age-matched lambs were used as controls. At 135-141 days GA (term=145 days), in utero ultrasonographic evaluation of the fetuses was performed. A Siemens Sequoia ultrasound system with a linear 10L4 SWE transducer was used to evaluate the peripheral right lower lobe stiffness at an imaging depth of 1-3 cm (Figure 1). Mean lung stiffness (kPa) was compared between the groups using one-way ANOVA. CDH was confirmed at necropsy. Total lung weight (TLW) and lung weight/body weight (LW/BW) were compared with Welch’s t-tests.

Results: 112 SWE measurements of the peripheral right lung were analyzed: 47 in fetuses with CDH and 65 in controls. There was a statistically significant increase in mean lung stiffness in CDH animals compared to controls (4.03 ± 1.19 kPa vs. 3.11 ± 0.59 kPa, p<0.001). Additionally, CDH animals demonstrated decreased mean TLW and LW/BW compared to controls (72.8g vs. 146.4g; p=0.02 and 1.7% vs. 2.6%; p=0.04).

Conclusion: Using SWE, increased lung stiffness was demonstrated in fetal lambs with left-sided CDH compared to controls. Severity of pulmonary hypoplasia was confirmed with corresponding decreased lung weight in CDH lambs.

Clinical Relevance/Application: SWE can be utilized as a noninvasive approach to evaluate pulmonary stiffness, which may correlate with pulmonary compliance in CDH. This technique could provide further insight into pulmonary mechanics and improve prenatal prognostication and postnatal management of children with CDH.