Assessment of First-Trimester Utero-Placental Vascular Morphology by 3D Power Doppler Ultrasound Image Analysis Using a Skeletonization Algorithm: The Rotterdam Periconception Cohort

Abnormal uteroplacental vascular development is one of the primary causes of the major disorders of pregnancy. Identification of this aberrant development in the preconception stage and in the first trimester, when measures to prevent complications are most effective, remains a challenge. Recent advances in offline imaging processing and Doppler techniques have allowed ultrasonographic analysis of placental volume (PV) and uteroplacental vascular volume (uPVV) in the first trimester. The ability of ultrasound to assess specific vascular morphology is not fully understood. The aim of this study was to investigate morphologic development of the first-trimester human uteroplacental vasculature in vivo using 3-dimensional power Doppler ultrasound and advanced image processing to generate the uteroplacental vascular skeleton (uPVS). Data were obtained from the VIRTUAL Placenta study, an ongoing observational study including adult women carrying a singleton pregnancy at less than 10-week gestational age (GA). At least 2 study visits were scheduled in the first trimester, at 7, 9, and 11 weeks' GA. The image quality of ultrasound scans was scored on a 4-point scale ranging between 0 (optimal) and 3 (unusable), and PV was measured using VOCAL software. The uPVV was measured using a virtual reality desktop system with the V-scope volume-rendering application. A skeletonization algorithm was then applied to the uPVV segmentation to generate the uPVS, and 7 morphological uPVS characteristics were used to determine the density of vascular branching within the placenta. A total of 214 women from the VIRTUAL cohort were eligible for inclusion, and 81% of all ultrasound data were of sufficient quality for generation of the uPVS. The distribution of endpoints, vessel points, bifurcation points, and crossing points in the uPVS and the distribution of uPVS characteristics per cm(3) uPVV show consistent morphologic patterns throughout the first trimester. Moderate to strong positive correlations between uPVS characteristics and PV and strong positive correlations between uPVS characteristics and uPVV were identified. All uPVS characteristics increased significantly through the first trimester, except for uPVS average length, which remained constant between 7, 9, and 11 weeks' GA. When stratifying for placenta-related complications among the cohort, no significant differences in the uPVS characteristics were seen at 7 weeks' GA (n = 94). However, at 9 weeks (n = 170), there were significantly fewer number of vessel points (P = 0.040), bifurcation points (P = 0.050), crossing points (P = 0.020), and a shorter total network length (P = 0.023) among pregnancies with placenta-related complications. At 11 weeks' GA (n = 129), uPVS average vascular thickness was significantly lower in pregnancies with placenta-related complications (P = 0.007), but no other uPVS differences were observed. At 11 weeks' GA, pregnancies with placenta-related complications were found to have an increased density of vascular branching in the uPVV. The results of this study demonstrate a quantitative morphologic analysis of the human uteroplacental vasculature in the first trimester of pregnancy and key differences in the vascular morphology between pregnancies with and without placenta-related complications.