106: Novel MRI detection of impaired placental blood flow and fetal oxygen reserve in a non-human primate model of gestational protein restriction

Abstract

We have recently developed novel placenta-specific MRI protocols to estimate placental oxygen reserve using blood oxygenation levels (T2* imaging). High oxyhemoglobin concentration has long T2* and correlates with areas of high perfusion as validated by dynamic contrast enhanced (DCE) MRI. Short T2* relates to areas of high deoxyhemoglobin concentration. Here our objective was to evaluate the adverse effects of maternal malnutrition on placental oxygen reserve and placental perfusion in vivo in a non-human primate model of gestational protein restriction (PR). Rhesus macaques were fed a control diet (CON, 26% protein, n=8) or switched to either a 33% PR (17% protein, n=8) or 50% PR (13% protein, n=8) diet before and during pregnancy. All underwent Doppler ultrasound (D-US) and fetal biometry measurements followed by MRI consisting of T2* and DCE measurements at gestational day 85 (G85) and G135 (term is G168). D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume blood flow (cQuta) and placental volume blood flow (cQuv). Pregnancy loss rates were 0/8 in controls, 1/8 in 33% PR, and 3/8 in 50% PR (1 prior to G135). Animals fed a 50%PR diet had significantly smaller fetal abdominal circumference (G135) and lower cQuta (G135) and cQuv (G85 and G135) versus CON (Fig 1). Additionally, by DCE-MRI, placental blood flow was significantly lower at G135 in animals fed a 50% PR diet (Fig 1). Distributions of T2* throughout the placenta (Fig 2) show significant global reductions in T2* (blood oxyhemoglobin) in animals fed a 50% PR diet vs. CON (G85 and G135). These data from a relevant translational model demonstrate that a 50% gestational PR diet reduces maternal placental perfusion, decreases fetal oxygen availability and increases fetal mortality. However, animals fed a 33% PR diet were similar to CON suggesting that placental reserve capacity is able to compensate for some PR, but not a 50% reduction. The perturbations observed with placental blood flow and fetal oxygen availability may explain the noted increased risk of human growth restriction and stillbirth with severe PR diets in the developing world. Our imaging abilities have allowed early identification of pregnancies affected by placental dysfunction and is a first step in improving outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)