Assessment of fetal and placental blood flow in primates using contrast enhanced ultrasonography

Ultrasonographic contrast agents that stay within the vascular space and do not cross the placenta may permit differentiation between the maternal and fetal portions of the placenta and may be clinically useful for diagnosis of placental abnormalities. This study was performed to assess the effects of Levovist (Schering AG, Berlin) on the placental circulation and to determine whether hemodynamic effects on the fetus occur. Ten studies were performed in five pregnant macaques (median weight, 9.15 kg; range, 6.15 to 11 kg; median gestational age, 121 days; range, 34 days to term) under anesthesia. Gray scale, color, and duplex Doppler sonographic scans of the fetus and placenta were acquired using a 5 MHz curved array transducer. Fetal heart rate, resistive index, and systolic-diastolic ratios were measured in the fetal middle cerebral artery, aorta, umbilical artery, and uterine artery before and after administration of contrast agent. The following dose regimen was tested: 5 ml of physiologic saline solution followed by 0.1 ml/kg of 300 mg/ml Levovist (diagnostic dose), 0. 5 ml/kg of 400 mg/ml Levovist (maximum dose), and 5 ml physiologic saline solution. The order of diagnostic dose and maximal dose was randomized among animals. Color enhancement of the basal portions of the placenta was documented after administration of contrast agent. Heart rate and middle cerebral artery systolic-diastolic ratio did not change between baseline and injections. A 7% decrease of the resistive index from baseline to maximum dose was measured in the uterine artery (not significant). A 7.7% decrease in the systolic-diastolic ratio from baseline to maximum dose was recorded in the umbilical artery. However, an identical change was measured after saline solution was injected. The resistive index in the aorta increased by 2.6% from baseline to maximum dose, a change that was not significant (P > 0.5). Ultrasonographic contrast enhancement of the maternal circulation in placenta is demonstrated to be without significant effects on the fetal circulation as measured in this limited population.