Placental MRI Predicts Fetal Oxygenation and Growth Rates in Sheep and Human Pregnancy

Abstract

Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO 2 ) 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 SO 2 . Birth weight is collected and, in sheep, fetal blood SO 2 is measured with a blood gas analyzer (BGA). Fetal arterial SO 2 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 SO 2 in late gestation is related to fetal blood SO 2 measured by BGA and body weight. In sheep, MRI feto-placental SO 2 in mid-gestation is related to fetal SO 2 later in gestation. MRI feto-placental SO 2 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 SO 2 and distinguishes between small hypoxemic fetuses and normally grown fetuses.

Advanced imaging of fetal cardiac function

“…Acquiring Doppler spectra with correct alignment can be challenging in the fetus, although mathematical angle corrections are possible ( 96 ). In fetal hypoxia, deep or reversed a-waves in the ductus venosus and pulsatile flow in the umbilical vein reflect cardiac dysfunction ( 64 , 97 – 99 ) and correlate with poor fetal outcomes ( 18 , 85 , 100 ). Similarly, middle cerebral artery pulsatility is reduced due to cerebral vasodilation or “brain-sparing physiology” in the setting of fetal hypoxemia secondary to placental insufficiency or other causes ( 82 , 93 , 101 – 103 ).…”

“…A combination of vessel flow and magnetic resonance oximetry has also been applied in sheep to assess the distribution of blood flow and oxygen transport across the fetal circulation, and as an approach to comprehensively quantifying the placental oxygen transfer (31,(46)(47)(48)(49)(50)(51). Fetal CMR has been used in human pregnancies to study the effect of congenital cardiac malformations on fetal cardiovascular physiology, particularly through the implementation of cine phase contrast for quantifying vessel flow and relaxometry for characterizing vessel oxygen saturation and hematocrit, techniques that have also been applied in the setting of fetal growth restriction and anemia (19,25,29,33,37,38,50,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64).…”

Phenotype of early-onset fetal growth restriction in sheep

“…The use of preclinical animal models of pregnancy and birth compromise allows specific characterisation of how structural deficits underpin functional deficits of multiple organ systems including the brain, heart and lungs ( 27 , 32 , 50 , 59 – 61 ). In animal experiments, the wellbeing of the fetus can be monitored in utero , postnatal clinically applicable assessments such as MRI and haemodynamic monitoring can be performed ( 62 – 64 ), and these can all be correlated with cellular level assessment of structural alterations in organs collected at post-mortem ( 64 , 65 ). Such studies to reveal fundamental relationships between organ structure and function are essential to better our understanding of how fetal compromise alters the trajectory of development, and these studies cannot be undertaken in humans.…”

The effect of maternal position on placental blood flow and fetoplacental oxygenation in late gestation fetal growth restriction: a magnetic resonance imaging study

“…Therefore, measuring FO 2 with DECIDE MRI may provide an earlier and more direct indication of the degree of placental dysfunction and fetal hypoxaemia than that which becomes apparent using Doppler ultrasound, which is also highly user‐dependent (Browne et al., 2015). A prior study in sheep and humans conducted an assessment of the relationship between DECIDE parameters and fetal weight, and showed that fractional parameters v and f did not relate to fetal weight (Flouri et al., 2022). Diffusivity values represent the micro‐environment of the placenta, with lower values reflecting reduced diffusion of water/blood, and in FGR pregnancies changes in these values may be driven by a reduced fetal blood volume, or as observed anatomically, be due to lower calibre fetoplacental blood vessels (Kingdom et al., 2000).…”

“…Diffusivity values represent the micro-environment of the placenta, with lower values reflecting reduced diffusion of water/blood, and in FGR pregnancies changes in these values may be driven by a reduced fetal blood volume, or as observed anatomically, be due to lower calibre fetoplacental blood vessels (Kingdom et al, 2000). Blood gas sampling in sheep indicates that DECIDE FO 2 is a good predictor of measured blood gases, and so this parameter is likely to be useful for distinguishing fetal hypoxia in the growth-restricted fetus from constitutionally small but normoxic fetuses (Flouri et al, 2022). Placental flux quantifies the diffusive movement of oxygen within the placenta, and its transfer across the villous membrane into fetal blood.…”