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


METHODS
Ten pregnant Merino sheep underwent surgery to implant arterial catheters in the target fetuses. Anesthetized ewes underwent 4D flow CMR with acquisition at 3 T for fetal whole-heart coverage with 1.2-1.5 mm spatial resolution and 45-62 ms 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.


RESULTS
Streaming 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 546 mL/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 14.2 ± 12.1%. Compared with 2D PC CMR, 4D flow showed a strong correlation (R2 = 0.85) but underestimated flow (bias = - 21.88 mL/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.
['Schrauben|Eric M|EM|0000-0002-3993-0497', 'Saini|Brahmdeep Singh|BS|', 'Darby|Jack R T|JRT|', 'Soo|Jia Yin|JY|', 'Lock|Mitchell C|MC|', 'Stirrat|Elaine|E|', 'Stortz|Greg|G|', 'Sled|John G|JG|', 'Morrison|Janna L|JL|', 'Seed|Mike|M|', 'Macgowan|Christopher K|CK|']
D000818:Animals D001783:Blood Flow Velocity D001808:Blood Vessels D003326:Coronary Circulation D005260:Female D005318:Fetal Heart D005865:Gestational Age D006340:Heart Rate, Fetal D006439:Hemodynamics D008279:Magnetic Resonance Imaging D055414:Myocardial Perfusion Imaging D011237:Predictive Value of Tests D011247:Pregnancy D011296:Prenatal Diagnosis D034561:Sheep, Domestic
Fetal Hemodynamics Cardiac Cardiovascular magnetic resonance 4D flow CMR