Purpose or Case Report: Assessment of fetal brain perfusion with contrast-enhanced ultrasound (CEUS) has not been performed in vivo in congenital diaphragmatic hernia (CDH). The development of the EXTra-uterine Environment for Neonatal Development allows investigation of CEUS and fetal brain perfusion parameters. The purpose of this study was to assess for aberrations in brain perfusion using CEUS in fetal lambs with CDH and correlate with cardiac output data.
Methods & Materials: Following IACUC-approved protocols, 4 fetal lambs underwent surgical CDH creation at 71-76 days gestational age (GA) and were transferred from placental support to the EXTEND system at 115-120 days GA and maintained per protocol. 4 lambs without CDH served as controls. At 115-130 days GA, 0.9-1.3mL Definity® US contrast mixed in 50mL of saline was administered by infusion at 100-120mL/hr depending on estimated weight. Flash-replenishment CEUS cine clips (15 sec; in triplicate) were acquired using a GE Logiq E9 US system and a C2-9 transducer and analyzed with post-processing software developed in MATLAB. Time-intensity-curves were used to generate metrics including flux rate (FR), transit time (TT), and perfusion. CEUS parameters were compared between groups with univariate analyses and repeated measures ANOVA. Right-to-left ventricular cardiac output (RLCO) was calculated by daily echocardiogram.
Results: 206 CEUS examinations were quantified, of which 169 were considered adequate with curve fit r²≥0.9 and included in analyses. CDH animals demonstrated similar FR (median 0.65, IQR 0.56-0.74; vs. 0.65, IQR 0.57-0.72 a.u./sec; p=0.9), similar TT (median 2.14, IQR 1.87-2.48 vs. 2.14, IQR 1.94-2.48) sec; p=0.8), and slightly increased perfusion (median 54.2, IQR 44-65 vs. 49.9, IQR 40-66; p=0.6) when compared to controls. However, in CDH animals, GA was correlated with FR, TT, and perfusion (all p≤0.01). Models showed progressively decreased TT with GA in CDH animals (p<0.01) and increased TT in controls (p<0.01). Additionally, brain perfusion progressively increased with GA in CDH animals (p<0.01) while it decreased in controls (p=0.01). Mean RLCO was increased in CDH animals compared to controls [1.78 ± 0.51 vs. 1.46 ± 0.19; (p<0.01)].
Conclusions: Aberrant CEUS brain perfusion parameters are identified in CDH animals compared to controls. These perfusion parameters change with time suggesting progressive effects of CDH on cerebral blood flow, which may be partially explained by increased RLCO.