Whole organ vascular casting and microCT examination of the human placental vascular tree reveals novel alterations associated with pregnancy disease

Abstract

Experimental methods that allow examination of the intact vascular network of large organs, such as the human placenta are limited, preventing adequate comparison of normal and abnormal vascular development in pregnancy disease. Our aims were (i) to devise an effective technique for three-dimensional analyses of human placental vessels; (ii) demonstrate the utility of the technique in the comparison of placental vessel networks in normal and fetal growth restriction (FGR) complicated pregnancies. Radiopaque plastic vessel networks of normal and FGR placentas (n = 12/group) were created by filling the vessels with resin and corroding the surrounding tissues. Subsequently, each model was scanned in a microCT scanner, reconstructed into three-dimensional virtual objects and analysed in visualisation programmes. MicroCT imaging of the models defined vessel anatomy to our analyses threshold of 100 µm diameter. Median vessel length density was significantly shorter in arterial but longer in venous FGR networks compared to normals. No significant differences were demonstrable in arterial or venous tortuosity, diameter or branch density. This study demonstrates the potential effectiveness of microCT for ex-vivo examination of human placental vessel morphology. Our findings show significant discrepancies in vessel length density in FGR placentas. The effects on fetoplacental blood flow, and hence nutrient transfer to the fetus, are unknown.