Fetal hemodynamics and cardiac streaming assessed by 4D flow cardiovascular magnetic resonance in fetal sheep

BackgroundTo date it has not been possible to obtain a comprehensive 3D assessment of fetal hemodynamics because of the technical challenges inherent in imaging small cardiac structures, movement of the fetus during data acquisition, and the difficulty of fusing data from multiple cardiac cycles when a cardiac gating signal is absent. Here we propose the combination of volumetric velocity-sensitive cardiovascular magnetic resonance imaging (4D flow CMR) and a specialized animal preparation (catheters to monitor fetal heart rate, anesthesia to immobilize mother and fetus) to examine fetal sheep cardiac hemodynamics in utero.MethodsTen pregnant Merino sheep underwent surgery to implant arterial catheters in the target fetuses. Anesthetized ewes underwent 4D flow CMR with acquisition at 3T for fetal whole-heart coverage with 1.2-1.5mm spatial resolution and 45-62ms temporal resolution. Flow was measured in the heart and major vessels, and particle traces were used to visualize circulatory patterns in fetal cardiovascular shunts. Conservation of mass was used to test internal 4D flow consistency, and comparison to standard 2D phase contrast (PC) CMR was performed for validation.ResultsStreaming of blood from the ductus venosus through the foramen ovale was visualized. Flow waveforms in the major thoracic vessels and shunts displayed normal arterial and venous patterns. Combined ventricular output (CVO) was 546mL/min per kg, and the distribution of flows (%CVO) were comparable to values obtained using other methods. Internal 4D flow consistency across 23 measurement locations was established with differences of 14.212.1%. Compared with 2D PC CMR, 4D flow showed a strong correlation (R-2=0.85) but underestimated flow (bias=-21.88mL/min per kg, p<0.05).Conclusions The combination of fetal surgical preparation and 4D flow CMR enables characterization and quantification of complex flow patterns in utero. Visualized streaming of blood through normal physiological shunts confirms the complex mechanism of substrate delivery to the fetal heart and brain. Besides offering insight into normal physiology, this technology has the potential to qualitatively characterize complex flow patterns in congenital heart disease phenotypes in a large animal model, which can support the development of new interventions to improve outcomes in this population.