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 (VnormalO2) 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 VnormalO2 by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental VnormalO2 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 VnormalO2, which involves the quantification of maternal‐ and fetal‐placental blood flows, fetal oxygen delivery and VnormalO2, 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 (VnormalO2) 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 (DnormalO2) and VnormalO2 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 DnormalO2 and VnormalO2. Maternal DnormalO2 (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 DnormalO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VnormalO2 (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 VnormalO2 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 VnormalO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VnormalO2 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 VnormalO2 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’.

Breath of Life: Heart Disease Link to Developmental Hypoxia

“… 108 In recent years, several magnetic resonance imaging approaches for the assessment of placental function and fetal cardiovascular physiology in sheep have also been developed. 109 These noninvasive techniques provide indispensable approaches to identifying placental and fetal cardiometabolic dysfunction in complicated pregnancy. Such technologies hold significant promise which will help in the translation of potential interventions, such as the use of mitochondria-targeted antioxidants, into the human clinical situation.…”

Placental pathologic lesions associated with stroke in term neonates

“…Placental pathology may provide input into a stroke risk stratification algorithm, but the timeframe required for placental examination will be a limiting factor until new techniques are developed that can offer real-time, clinically-relevant information. In order to establish preventative strategies, advanced methods of in utero assessment are needed, such as the many emerging methods in advanced placental magnetic resonance imaging ( 43 – 46 ).…”

Maternal sleep behaviours preceding fetal heart rate events on cardiotocography

“…Given the limitations in assessing human placental function non‐invasively, recent studies have demonstrated the feasibility of using MRI to measure blood flow and oxygen content in the uterine and umbilical vessels to calculate oxygen delivery and uteroplacental oxygen consumption (Saini et al . 2020, 2021). While these innovative techniques may be able to better quantify the impact of maternal positioning on fetal wellbeing, the difficulty lies in applying these techniques to a maternal sleep state where cardiovascular and respiratory function is altered.…”

“…Interpretation of the CTG in an antenatal setting can be challenging, but the pathophysiological adaptations and responses of the fetus seen intrapartum can be extrapolated to the antenatal setting to provide a real-time assessment of fetal wellbeing to hypoxic challenges (Judd et al 2020). Given the limitations in assessing human placental function non-invasively, recent studies have demonstrated the feasibility of using MRI to measure blood flow and oxygen content in the uterine and umbilical vessels to calculate oxygen delivery and uteroplacental oxygen consumption (Saini et al 2020(Saini et al , 2021. While these innovative techniques may be able to better quantify the impact of maternal positioning on fetal wellbeing, the difficulty lies in applying these techniques to a maternal sleep state where cardiovascular and respiratory function is altered.…”