Assessment of placenta vascularization development using contrast-enhanced ultrasound

During gestation, the uterine vasculature undergoes numerous physiologic modifications in order to bring the necessary quantitative increase in blood flow to support placental development. The spiral arteries are remodeled from tightly coiled, tonically active vessels to wide-bore tubes that lack responsiveness to maternal

tonic signals. Also, the larger vessels (uterine, arcuate, and radial arteries) dilate to increase the amount of blood supplying the uterus. Preeclampsia and intrauterine growth restriction are two principal complications of pregnancy. These diseases are related to chronic uteroplacental hypoperfusion, but knowledge of the

pathophysiological mechanisms involved remains inadequate. During uteroplacental vascularization, the most prominent and important process is the spiral arteries remodeling. The spiral arteries undergo a generalized, but non-uniform, dilation as pregnancy advances, with considerable variation in size between arteries within the

same specimen, and even at different points along individual arteries. The remodeling enables a continuous high volume of maternal blood flow through the placenta after onset of the circulation, but presumably at a low velocity and pressure that avoids mechanical damage to the villous trees and allows an adequate transit time for

maternal-fetal exchange. Despite the importance of uteroplacental vascularization in maternal-fetal health, there is a paucity of safe and noninvasive imaging tools to assess it in real-time. To date, ultrasound Doppler techniques are most commonly utilized to demonstrate and quantify blood flow during the uteroplacental

vascularization. However, Doppler indices show variability due to operator and system settings. Moreover, Doppler signals from low velocity microvessels are often missed or misinterpreted. Thus, we propose a new imaging tool to assess placental hemodynamics based on the pressure estimation using contrast-enhanced

ultrasound (CEUS). CEUS uses microbubbles, whose main purpose is to enhance the backscattered signals in blood vessels allowing improved vascularity assessment by ultrasound imaging. However, microbubbles can also act as pressure sensors, due to the difference in compressibility between the bubble and the surrounding

medium. Our group has developed the fundamental concept of subharmonic (half of fundamental frequency) aided pressure estimation (SHAPE) using this oscillating characteristic of microbubbles. The SHAPE technique estimates ambient pressure using the subharmonic amplitude from CEUS through this inverse relationship

measured at each target location in real-time. This study aims to determine if the SHAPE can become a safe, noninvasive, and real-time tool to assess human uteroplacental vascularization in early pregnancy. We suggest using mean pressure gradients between the uterine artery, placental bed (arteries in decidua and myometrium),

and intervillous space as our functional indices as well as the standard deviation of pressure estimates in the placental bed. We hypothesize that these indices will correlate with the degree of uteroplacental vascularization, i.e., with gestational age in normal pregnancy.