Longitudinal characterization of local perfusion of the rat placenta using contrast-enhanced ultrasound imaging

Abstract

The placenta performs many physiological functions critical for development. Insufficient placental perfusion, due to improper vascular remodelling, has been linked to many pregnancy-related diseases. To study longitudinal in vivo placental perfusion, we have implemented a pixel-wise time-intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) images. CEUS images were acquired of pregnant Sprague Dawley rats after bolus injections of gas-filled microbubble contrast agents. Conventionally, perfusion can be quantified using a TIC of contrast enhancement in an averaged region of interest. However, the placenta has a complex structure and flow profile, which is insufficiently described using the conventional technique. In this work, we apply curve fitting in each pixel of the CEUS image series in order to quantify haemodynamic parameters in the placenta and surrounding tissue. The methods quantified an increase in mean placental blood volume and relative blood flow from gestational day (GD) 14 to GD18, while the mean transit time of the microbubbles decreased, demonstrating an overall rise in placental perfusion during gestation. The variance of all three parameters increased during gestation, showing that regional differences in perfusion are observable using the pixel-wise TIC approach. Additionally, the high-resolution parametric images show distinct regions of high blood flow developing during late gestation. The developed methods could be applied to assess placental vascular remodelling during the treatment of the pathologies of pregnancy.

Keywords: contrast-enhanced ultrasound; functional imaging; perfusion; placenta; vascular flow.

Figure 1.

(a) B-mode US image of the placental environment on GD 14. (b) After microbubble administration, CEUS signal can be identified in the spiral arteries (smallest ROI, in orange online), and central arterial canal (T-shaped ROI, in green online) of the placenta (kidney-shaped ROI, in blue online). (c) The CEUS image overlay shows the frame of peak contrast signal in the placenta (p) when microbubbles have filled the intervillous space. No CEUS signal was detected in the fetus (f). Scale bars indicate 3 mm. (Online version in colour.)

Figure 2.

Data processing sequence for the pixel-wise TIC analysis of placental perfusion. (Online version in colour.)

Figure 3.

Example TIC fit of the lognormal function (blue line) to the linearized CEUS signal intensity. Intensity values (arb. units) have been normalized for display. (Online version in colour.)

Figure 4.

Parametric images of relative blood flow (RBF) superimposed on B-mode US images of the placental environment on GD 14 (a), GD 16 (b), and GD 18 (c). The rectangle (in yellow online) indicates the ROI where CEUS images were acquired. The bar graphs display the mean and normalized variance in blood flow increases in the placenta during gestation. Data shown as log scaled mean ± SEM. Scale bars = 3 mm. (Online version in colour.)

Figure 5.

Parametric images of peak enhancement (PE), representative of local blood volume, superimposed on B-mode US images of the placenta on GD 14 (a), GD 16 (b) and GD 18 (c). The rectangle (in yellow online) indicates the ROI where CEUS images were acquired. The bar graphs display the mean and normalized variance of PE in the placenta during gestation. Data shown as log scaled mean ± SEM. Scale bars = 3 mm. (Online version in colour.)

Figure 6.

Parametric images of mean transit time (MTT) superimposed on B-mode US images of the placental environment on GD 14 (a), GD 16 (b) and GD 18 (c). The rectangle (in yellow online) indicates the ROI where CEUS images were acquired. The bar graphs display the mean and normalized variance of the MTT. The MTT decreases during gestation while variance increases, indicating that MBs circulate through placental microvasculature more quickly. Data shown as mean ± SEM. Scale bars = 3 mm. (Online version in colour.)