Perfusion of the placenta assessed using arterial spin labeling and ferumoxytol dynamic contrast enhanced magnetic resonance imaging in the rhesus macaque.

PURPOSE: To investigate the correspondence between arterial spin labeling (ASL) flow-sensitive alternating inversion recovery (FAIR) and ferumoxytol DCE MRI for the assessment of placental intervillous perfusion. METHODS: Ten pregnant macaques in late second trimester were imaged at 3 T using a 2D ASL FAIR, with and without outer-volume saturation pulses used to control the bolus width, and a 3D ferumoxytol DCE-MRI acquisition. The ASL tagged/control pairs were averaged, subtracted, and normalized to create perfusion ratio maps. Contrast arrival time and uptake slope were estimated by fitting the DCE data to a sigmoid function. Macaques (N = 4) received interleukin-1ß to induce inflammation and disrupt perfusion. RESULTS: The FAIR tag modification with outer-volume saturation reduced the median ASL ratio percentage compared with conventional FAIR (0.64% ± 1.42% versus 0.71% ± 2.00%; P < .05). Extended ferumoxytol arrival times (34 ± 25 seconds) were observed across the placenta. No significant DCE signal change was measured in fetal tissue ( - 0.6% ± 3.0%; P = .52) or amniotic fluid (1.9% ± 8.8%; P = .59). High ASL ratio was significantly correlated with early arrival time and high uptake slope (P < .05), but ASL signal was not above noise in late-DCE-enhancing regions. No significant differences were observed in perfusion measurements between the interleukin-1ß and controls (P > .05). CONCLUSION: The ASL-FAIR and ferumoxytol DCE-MRI methods are feasible to detect early blood delivery to the macaque placenta. Outer volume saturation reduced the high macrovascular ASL signal. Interleukin-1ß exposure did not alter placental intervillous perfusion. An endogenous-labeling perfusion technique is limited due to extended transit times for flow within the placenta beyond the immediate vicinity of the maternal spiral arteries.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.