Abstract Magnetic resonance imaging provides a new perspective on abnormal fetal cardiovascular physiology resulting from congenital heart disease Using a combination of cine phase contrast MRI for vessel flow quantification and relaxometry for oximetry and blood oxygen content measurement it has been possible to reproduce prior fetal sheep invasive hemodynamic measurements in humans These have revealed that a combination of placental dysfunction, reduced umbilical perfusion and interruption of the normal streaming of oxygenated blood towards the cerebral circulation is associated with delayed brain growth and development Thus, fetal interventions aimed at improving cerebral oxygenation in fetuses with congenital heart disease could be helpful in preventing the adverse neurodevelopmental outcomes seen in many children with congenital heart disease Keywords fetal circulation; phase contrast; magnetic resonance oximetry; in utero brain development Introduction The ability to accurately measure blood flow and oxygen saturations across the human late-gestation fetal circulation offered by advances in magnetic resonance imaging (MRI) has provided new insights into the impact of congenital heart disease (CHD) on the developing fetus MRI has demonstrated redistribution of blood flow and interruption of the normal streaming of blood resulting from the obstructions to flow and abnormal connections that characterize CHD Abnormal fetal hemodynamics have been linked to the dysmaturation of the lungs and brain that are typical of newborns with more severe forms of CHD We have also learned how diminished cardiac output in fetuses with single-ventricle physiology is associated with reduced fetal perfusion of the placenta and impaired placental oxygen exchange, which may account for the growth restriction typical of late-gestation fetuses with these types of cardiac malformations Recent data indicate that an impaired maternal-fetal environment may have an important impact on congenital cardiac surgical results.1 These observations are likely to be of relevance as we seek to understand better the risk factors for adverse outcomes of neonatal cardiac surgery and develop new therapies to alter the natural history of CHD prior to birth Normal Fetal Circulatory Physiology Much of what is known about fetal cardiovascular physiology has been learned through invasive experiments performed in sheep Elaborating on methods for exteriorizing and catheterizing the fetal lamb developed by Joseph Barcroft and Geoffrey Dawes at Cambridge and Oxford universities, Abraham Rudolph and his coinvestigators at the Cardiovascular Research Institute at the University of California, San Francisco, defined our modern understanding of the distribution of blood flow and oxygen transport across the fetal circulation.2 Rudolph's flow measurements were achieved through the selective injection of radioactive microspheres into different venous compartments that were subsequently trapped in the microcirculation of the end organs supplied by the fetal heart By measuring the relative activity of the different tracers in each of the various fetal organs and applying the Fick principle to measure umbilical flow, blood flow in each of the major vessels was calculated These flow measurements were combined with blood pressure measurements and oximetry performed by conventional blood gas analysis of samples obtained using catheters placed in the fetal vessels Based on observations regarding differences between the species, including the size of the fetal brain and hematocrit, Rudolph then predicted the distribution of blood flow and oxygen saturations across the human fetal circulation To summarize, the fetal circulation operates in parallel, with shunts at the ductus venosus, foramen ovale, and ductus arteriosus, which allow well-oxygenated blood returning from the placenta to pass directly to the most metabolically active fetal organs, the heart and brain, while deoxygenated blood is directed back to the placenta In the fetus, the blood with the highest oxygen saturation of approximately 85% is found in the umbilical vein and, downstream, the oxygen saturation is 10% to 15% higher in the left heart (65%) than the right (55%) (see Video 7.1) In fetal sheep, this is achieved by a remarkable streaming of blood emerging from the ductus venosus and left hepatic vein toward the foramen ovale, while more deoxygenated blood passes from the infrahepatic inferior vena cava and right hepatic vein toward the tricuspid valve In fetal sheep, the right ventricle provides the more dominant contribution (approximately two-thirds) toward the combined ventricular output, the majority of which passes into the ductus arteriosus and descending aorta Rudolph suggested that the right ventricle was also dominant in the human, with about 15% of the combined ventricular output passing into the pulmonary circulation,