Contrast-enhanced ultrasound reveals real-time spatial changes in vascular perfusion during early implantation in the macaque uterus

Abstract

Objective: To use contrast-enhanced ultrasound (CEU) to quantify blood flow in the macaque uterus during early pregnancy.

Design: Prospective nonhuman primate study.

Setting: Oregon National Primate Research Center.

Animals: Naturally cycling female rhesus macaques (Macaca mulatta).

Intervention(s): Female macaques were mated on days 11-14 of the cycle. Females were then imaged by CEU and Doppler ultrasound once every 3 days from day 21 through day 39 of the fertile cycle.

Main outcome measure(s): Visualization and quantification of uterine vascular perfusion.

Result(s): CEU identified the primary placental disc and underlying vessels approximately 2 days earlier than Doppler ultrasound was able to observe endometrial thickening. CEU revealed spatial differences in vascular perfusion between the endometrium, myometrium, and endometrial-myometrial (junctional) zone. Myometrium displayed the highest rate of blood flow (>10 mL/min/g tissue). There was less blood flow in the endometrium and junctional zone (<3 mL/min/g). A brief fall in progesterone was observed during early implantation, which was correlated with reduced blood flow to all three uterine compartments, but did not reduce flow to the placenta.

Conclusions: CEU provides a sensitive, noninvasive method to assess vascular perfusion of the uterus during embryo implantation in macaques. We propose CEU as a new diagnostic tool to monitor vascular changes associated with early pregnancy in women.