An MRI approach to assess placental function in healthy humans and sheep

Abstract

Key points: Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ((Formula presented.)) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and (Formula presented.) by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental (Formula presented.) by MRI was ∼4 ml min−1 kg−1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental (Formula presented.), which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and (Formula presented.), and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. Abstract: It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ((Formula presented.)) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ((Formula presented.)) and (Formula presented.) in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal (Formula presented.) and (Formula presented.). Maternal (Formula presented.) (ml min−1 kg−1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal (Formula presented.) (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal (Formula presented.) (ml min−1 kg−1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal (Formula presented.) ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min−1 kg−1 fetus) decreased with advancing age (P = 0.008), while fetal (Formula presented.) was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal (Formula presented.) was preserved through stable umbilical flow (ml min−1 kg−1; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal (Formula presented.) between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical ‘placental function test’.