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Abstract Increasing placental perfusion (PP) could improve outcomes of growth‐restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)‐5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116–117 days’ gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120–123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15–75 min (TAD 1) and ∼75–135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion‐Relaxation Combined Imaging for Detailed Placental Evaluation—‘DECIDE’ technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal‐placental blood volume fraction was increased in the TAD 2 period. Fetal DO2 and V̇O2 were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal–placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA DO2.

Abstract Babies born growth restricted are at an increased risk of both poor short‐and long‐term outcomes. Current interventions to improve fetal growth are ineffective and do not lower the lifetime risk of poor health status. Maternal resveratrol (RSV) treatment increases uterine artery blood flow, fetal oxygenation, and fetal weight. However, studies suggest that diets high in polyphenols such as RSV may impair fetal hemodynamics. We aimed to characterize the effect of RSV on fetal hemodynamics to further assess its safety as an intervention strategy. Pregnant ewes underwent magnetic resonance imaging (MRI) scans to measure blood flow and oxygenation within the fetal circulation using phase contrast‐MRI and T2 oximetry. Blood flow and oxygenation measures were performed in a basal state and then repeated while the fetus was exposed to RSV. Fetal blood pressure and heart rate were not different between states. RSV did not impact fetal oxygen delivery (DO2) or consumption (VO2). Blood flow and oxygen delivery throughout the major vessels of the fetal circulation were not different between basal and RSV states. As such, acute exposure of the fetus to RSV does not directly impact fetal hemodynamics. This strengthens the rationale for the use of RSV as an intervention strategy against fetal growth restriction.

Over recent decades, a variety of advanced imaging techniques for assessing cardiovascular physiology and cardiac function in adults and children have been applied in the fetus. In many cases, technical development has been required to allow feasibility in the fetus, while an appreciation of the unique physiology of the fetal circulation is required for proper interpretation of the findings. This review will focus on recent advances in fetal echocardiography and cardiovascular magnetic resonance (CMR), providing examples of their application in research and clinical settings. We will also consider future directions for these technologies, including their ongoing technical development and potential clinical value.

Abstract Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO2) can transform the clinical management of high‐risk pregnancies affected by fetal growth restriction (FGR). Here, a novel MRI method assesses the feasibility of identifying normally grown and FGR fetuses in sheep and is then applied to humans. MRI scans are performed in pregnant ewes at 110 and 140 days (term = 150d) gestation and in pregnant women at 28+3 ± 2+5 weeks to measure feto‐placental SO2. Birth weight is collected and, in sheep, fetal blood SO2 is measured with a blood gas analyzer (BGA). Fetal arterial SO2 measured by BGA predicts fetal birth weight in sheep and distinguishes between fetuses that are normally grown, small for gestational age, and FGR. MRI feto‐placental SO2 in late gestation is related to fetal blood SO2 measured by BGA and body weight. In sheep, MRI feto‐placental SO2 in mid‐gestation is related to fetal SO2 later in gestation. MRI feto‐placental SO2 distinguishes between normally grown and FGR fetuses, as well as distinguishing FGR fetuses with and without normal Doppler in humans. Thus, a multi‐compartment placental MRI model detects low placental SO2 and distinguishes between small hypoxemic fetuses and normally grown fetuses.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Abstract The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA. This was performed in Large White‐Landrace‐Duroc piglets (n = 34) spanning four age groups: term‐9 days, term‐3, term+1, and term+5. Subject's DA status was classified using 4D flow: closed DA, forward DA flow, reversed DA flow, and bidirectional DA flow. Over all states, vessel diameters and flows normalized to body weight increased with age (for example in the ascending aorta flow—term‐9: 126.6 ± 45.4; term+5: 260.2 ± 80.0 ml/min per kg; p = 0.0005; ascending aorta diameter—term‐9: 5.2 ± 0.8; term+5: 7.7 ± 0.4 mm; p = 0.0004). In subjects with reversed DA blood flow there was lower common carotid artery blood flow (forward: 37.5 ± 9.0; reversed: 20.0 ± 7.4 ml/min per kg; p = 0.032). Linear regression revealed that as net DA flow decreases, common carotid artery flow decreases (R2 = 0.32, p = 0.004), and left (R2 = 0.33, p = 0.003) and right (R2 = 0.34, p = 0.003) pulmonary artery flow increases. Bidirectional DA blood flow changed oxygen saturation as determined by MRI between the ascending and descending aorta (ascending aorta: 90.1% ± 8.4%; descending aorta: 75.6% ± 14.2%; p

Abstract Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low‐resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way. Preterm Yucatan miniature piglets are similar in size to extremely preterm human infants and share similar umbilical cord anatomy, raising the possibility to serve as a good model to investigate the AP. To characterize fetal cardiovascular physiology, the carotid artery (n = 24) was cannulated in utero and umbilical vein (UV) and umbilical artery were sampled. Fetal UV flow was measured by MRI (n = 16). Piglets were delivered at 98 ± 4 days gestation (term = 115 days), cannulated, and supported on the AP (n = 12) for 684 ± 228 min (range 195–3077 min). UV flow was subphysiologic (p = .002), while heart rate was elevated on the AP compared with in utero controls (p = .0007). We observed an inverse relationship between heart rate and UV flow (r2 = .4527; p