In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study

Abstract

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.

Conflict of interest statement

J. Luo, E. Abaci Turk, P.E. Grant, N. Malpica, and E. Adalsteinsson are co-inventors on a patent applications describing the MRI based method for measuring placental transport.

Figures

Figure 1

Schematic diagrams depicting (A) the main components of a monochorionic diamniotic twin gestation. The magnified views in (B) represent the maternal placental circulation (left) and the fetal placental circulation (right) with an inset cartoon (C) representing oxygen transport from mother to the fetuses. Oxygen exchange between maternal hemoglobin and fetal hemoglobin by free diffusion across the interhemal membrane, and is modulated by the oxygen gradient, membrane permeability, and blood flow in both circulations.

Figure 2

Example cross-sections of a placenta (gestational age 31.4 weeks) during different stages of maternal hyperoxia. (A–C) BOLD images of the same cross-section view, at baseline (Fraction of inspired oxygen, FiO2 = 0.21), during hyperoxia (FiO2 = 1.0), and post hyperoxia. Dashed line in B defines the plane of section for images (D–F). (D–F) cross-sectional views orthogonal to (A–C) respectively. Note multiple hyperintense regions in a cotyledon-like distribution. The temporal pattern of signal instensity from baseline to hyperoxia and back is further investigated in the cotyledon circled in B and E in Supplementary Materials.

Figure 3

From left to right: BOLD images, TTP maps, histogram of TTP distribution and histology (10X). One control (top) is compared to one case with abnormal placental pathology (bottom). Yellow dashes in A and E outline the placenta. For healthy subjects, TTP values were short and placental histology was normal. For pathological cases, TTP values were longer and less uniform (blue regions in (F) and blue box in (G)). Arrows in H point to avascular villi and the star identifies chorangiosis.

Figure 4

Illustrations of segmentation volumes and of mean time-to-plateau (TTP). (A) placenta for the discordant twin pair with indication of ROI segmentation used for the average TTP calculation. (B) 3D view of segmented fetal brains and livers in the corresponding discordant twin pair (red points in (C–E) below). (C–E) Brain volume, liver volume and birth weight respectively as a function of the average TTP. The brain and liver volume were measured at the time of the scan. Twin pairs are connected by solid line, and are assigned same color. Hollow circles denotes fetuses that proved to be SGA at birth.

Figure 5

Time activity curves of placentas and fetal organs presented as signal intensity change relative to baseline (ΔR2*). Green: mean and standard deviation of ΔR2* for the organs of AGA fetuses; Red: mean and standard deviation of ΔR2* for the organs of SGA fetuses as defined retrospectively using birth weight. (A) placentas, (B) fetal livers, (C) fetal brain.