Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease

Abstract

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both p_FDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, p_FDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.

Figure 1

Placental schematic depicting placental anatomy and structures at ~ 32 weeks gestation (left), and the corresponding speculative tissue environments characterized by their T2*-ADC properties (right).

Figure 2

Plots showing mean placental and adjacent uterine wall T2* (top left), ADC (top right) and volume (bottom left) over gestation for all scans. Dotted lines join participants who had two scans.

Figure 3

Seven component InSpect fit to the whole placenta and uterine wall ROI data from 36 control participants, assuming the T2*‐ADC model described in Eq. (1). Top-row: T2*-ADC spectra for each component, which are shared across all 36 participants. Each T2*-ADC spectra represents the T2*-ADC distribution for that component, with each spectral peak reflecting a population with distinct T2* and ADC, and hence microstructural and microcirculatory, properties. Bottom row: plots showing the mean component weightings for each participant across gestation.

Figure 4

Placental composite images for two participants acquired at comparable gestational ages, showing the middle ten slices. Panel (A) is from a control participant, acquired at 34⁺³weeks. Panel (B) is from a CHD participant, acquired at 34⁺⁵weeks. The rows in panel A and B represent each component (1–7) and the columns represent slices through the ROI (left-to-right = anterior-to-posterior). Panel (C) and panel (D) show selected mid-placental slices from the same control (C) and CHD (D) dataset, highlighting the spatial location of each component at a gestational age of 34–35 weeks, with the columns representing components 1–7. The color scale (0–1) is the same for all images, representing the proportion of MR signal present in each voxel for each component.

Figure 5

Mean ROI (placenta and adjacent uterine wall) component weightings across gestation from 67 scans (50 control, 17 CHD). Component weighting ranges (y-axis) are kept consistent (0–80%) to aid interpretation as to the overall contribution to the MR signal from each component. Dotted lines join participants who underwent two scans.

Figure 6

Data flow. Manual regions of interest (ROI) (placental and adjacent uterine wall mask) overlaid on the first multi-dimensional volume (b = 0, TE = 78 ms) of the acquired diffusion-relaxation data (A), with the corresponding 3D-ROI rendering adjacent (B). After fitting Eq. (1) voxelwise to all voxels in this 3D-ROI, T2* and ADC maps were generated. These are shown for a selected coronal slice from a healthy placenta, acquired at 28⁺⁴weeks gestation (C). Subsequently, ‘full’ InSpect was run on data from 36 control participants, to generate the T2*-ADC spectra associated with each of the seven components (D), and also calculate the voxelwise weightings of each component, shown here for the same selected coronal slice (E). These spectra were then used to infer voxelwise spatial maps for all CHD scans and additional ‘repeat’ scans from the control sample (‘reduced InSpect’).