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. 2018 Jan 17;9:263. doi: 10.1038/s41467-017-02499-9

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Ultrasound and MR imaging of utero-feto-placental blood flow. a Uterine artery pulsatility index, b uterine artery blood flow volume (cQUtA) corrected for maternal body weight, c umbilical artery pulsatility index, and d umbilical vein blood flow volume (cQUV) corrected for fetal abdominal circumference measured by Doppler ultrasound in the ZIKV-exposed animals and a cohort of control, non-infected rhesus macaques (n = 6, black closed circles; mean ± SEM) across gestation. e Ultrasound images showing the appearance of the placenta (white outline) in a representative control uninfected dam (102dGA) and f a ZIKV-infected dam at 61dpi (112dGA). Both images were acquired at the same gain setting. g CE-US calculated microvascular flux rate from control (n = 27 spiral artery sources from n = 7 animals) and ZIKV-infected animals. Co-registered axial MRI images from animal D23046 are shown in h (T2w HASTE acquisition) and i (quantitative T2* map). Regions of interest (ROIs) delineating both placental lobes are indicated by the dashed green lines, and a focal region of pronounced hypoperfusion is circled. j Plots normalized histograms of placental relaxation rate (R2* = 1/T2*) for all five ZIKV-infected animals (colored curves), along with the median histogram for the six control animals (black curve). k Plots median values of PSv_i (averaged over all placental lobules) for each of the six control animals (black points) versus values for the five ZIKV-infected animals (colored points), stratified by gestational age at time of infection. l Shows relative blood flow for both the primary and secondary placental lobes in D23046 determined from DCE-MRI measurements for the perfusion domains corresponding to each placental lobule, as determined from DCE-MRI measurements. Darker shades indicated regions of the placenta that are hypoperfused. m Image of the fetal side of the placenta in this animal, demonstrating infarcted regions (white arrows) corresponding to the regions of hypoperfusion seen on DCE-MRI. Of note, ZIKV RNA was detected at five sites across the two placental lobes, indicated by the white asterisk. These ZIKV + areas predominantly correspond to hypoperfused cotyledons. p < 0.0001 one-way ANOVA with Tukey’s multiple comparison test, ***p < 0.001, **p < 0.01