Non‐invasive quantification of vascular reactivity in human placentas in utero

Abstract

ABSTRACTObjectiveMaintaining oxygen homeostasis across gestation, is one of the most critical functions of the placenta. Placental vascular reactivity (PLVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders are known to alter PLVR characteristics resulting in sub‐optimal oxygen delivery which consequently impairs fetal development. Our current understanding of PLVR characteristics, in healthy and pathological pregnancies, is limited by the lack of non‐invasive, repeatable methods to measure PLVR in utero.Our objective was to quantify PLVR by measuring placental response to transient changes in maternal CO2 using blood oxygen level dependent (BOLD) MRI. We hypothesized that (a) PLVR will increase with gestational age to meet the changing demands of a growing fetus; and (b) will be driven by maternal response to CO2 changes.MethodsThis is a cross‐sectional study of 34 women with healthy pregnancies with a mean gestational age of 32.6 weeks (22.6 to 38.4 weeks). Pregnant women were instructed to follow audiovisual breathing cues during the MRI. Maternal end‐tidal CO2 was measured concurrently with resting BOLD MRI of the placenta for a total of 7 minutes. Preprocessing of MRI images consisted of manual delineation of placental anatomy and motion correction. At each placental voxel, vascular reactivity was computed using coherence weighted general linear model between MRI signal and end‐tidal CO2 stimulus. Global placental vascular reactivity was computed as the mean of voxel wise vascular reactivity values across the placenta.ResultsPlacental vascular reactivity, quantified from the placenta's response to induced, transient changes in maternal CO2, can be measured consistently using MRI in utero. Placental vascular reactivity increases with gestational age (p<0.001) and was higher on the fetal‐facing side of the placenta compared to the maternal‐facing side.ConclusionWe present, for the first time, a non‐invasive paradigm to quantify placental vascular reactivity in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that placental vascular reactivity is driven by fetal response to changes in maternal CO2. Ease of clinical translation of our paradigm makes placental vascular reactivity a promising biomarker for the diagnosis and management of high‐risk pregnancies.This article is protected by copyright. All rights reserved.