Uteroplacental and Fetal 4D Flow MRI in the Pregnant Rhesus Macaque

Abstract

Background: Pregnancy complications are often associated with poor uteroplacental vascular adaptation and standard diagnostics are unable to reliably quantify flow in all uteroplacental vessels and have poor sensitivity early in gestation.

Purpose: To investigate the feasibility of using 4D flow MRI to assess total uteroplacental blood flow in pregnant rhesus macaques as a precursor to human studies.

Study type: Retrospective feasibility study.

Animal model: Fifteen healthy, pregnant rhesus macaques ranging from the 1^st trimester to 3^rd trimester of gestation.

Field strength/sequence: Abdominal 4D flow MRI was performed on a 3.0T scanner with a radially undersampled phase contrast (PC) sequence. Reference ferumoxytol-enhanced angiograms were acquired with a 3D ultrashort echo time sequence with a center-out radial trajectory.

Assessment: Repeatability of flow measurements was assessed with scans performed same-day and on consecutive days in the uterine arteries and ovarian veins. In-flow was compared against out-flow in the uterus, umbilical cord, and fetal heart with a conservation of mass analysis. Conspicuity of uteroplacental vessels was qualitatively compared between PC angiograms derived from 4D flow data and ferumoxytol-enhanced angiograms.

Statistical tests: Bland-Altman analysis was used to quantify same-day and consecutive-day repeatability.

Results: Same-day flow measurements showed an average difference between scans of 13% in both the uterine arteries and ovarian veins, while consecutive-day measurements showed average differences of 22% and 24%, respectively. Comparisons of in-flow and out-flow showed average differences of 15% in the uterus, 8% in fetal heart, and 15% in the umbilical cord. PC angiograms showed similar depiction of main uteroplacental vessels as high-resolution, ferumoxytol-enhanced angiograms.

Data conclusion: 4D flow MRI could be used in the rhesus macaque for repeatable flow measurements in the uteroplacental and fetal vasculature, setting the stage for future human studies.

Level of evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:534-545.

FIGURE 1

Vascular anatomy of the human placenta. Most of the maternal arterial blood in the placenta is supplied by the uterine arteries with additional contributions from the ovarian stem arteries. Corresponding veins run alongside these vessels. These vessels feed the spiral arteries, which drain into an intervillous space in the placenta where nutrients and oxygen can be transferred to and from the fetal circulation through two umbilical arteries and one umbilical vein in the umbilical cord. Measurement planes of interest to capture total uteroplacental and fetal-placental flow are marked by black bars. Although the rhesus macaque placenta has two distinct discs unlike the single disc in humans, the vascular anatomy is almost identical.

FIGURE 2

Representative PC MRA of three separate healthy pregnant rhesus macaques at different trimesters of gestation. The main arterial blood supply to the placenta appeared to be the uterine arteries (yellow), while the main venous return was through the ovarian veins (light blue). Uterine veins and ovarian stem arteries were not apparent. While fetal vessels (dark blue and red) were most notable around the 3^rd trimester, the main uteroplacental vessels were seen as early as late 1^st trimester.

FIGURE 3

Segmented PC angiogram of the fetal and umbilical vasculature in the early 3^rd trimester of pregnancy. The umbilical cord can be seen unbundling into one umbilical vein (red) and two umbilical arteries (blue), one of which forms the aortic arch, in the fetus. A corresponding slice from the PC VIPR magnitude images is shown at the right with the yellow arrows denoting placenta discs and the red arrow showing the umbilical cord.

FIGURE 4

PC angiograms in a single monkey across two days. Two angiograms were acquired on each day. The uterine arteries (yellow) showed minimal motion between days, while the ovarian veins (light blue) and the fetal and umbilical vessels (purple) showed more noticeable changes in position on subsequent days. Same day scans showed similar positioning of all vessels.

FIGURE 5

Comparison between ferumoxytol-enhanced angiogram (left) and PC angiogram (right) in the same rhesus macaque on the same day. The color scheme of the uteroplacental and fetal vessels is the same as in Figure 4, except in the ferumoxytol-enhanced angiogram where the uterine arteries and veins, which appear fused together, are a light red (white arrow).

FIGURE 6

Bland-Altman analysis of flow measurements in the uterine arteries from PC VIPR acquisitions. Repeatability results are presented for repeated scans (test-retest) on the same day and consecutive days, inter-observer analysis, and intra-observer analysis.

FIGURE 7

Bland-Altman analysis of flow measurements in the ovarian veins from PC VIPR acquisitions. Repeatability results are presented for repeated scans (test-retest) on the same day and consecutive days, inter-observer analysis, and intra-observer analysis.