Image-informed modelling of microscale exchange in the human placenta

The human placenta supports fetal development by mediating the exchange of gases, nutrients, drugs, and waste across a highly heterogeneous microscale interface formed by terminal villi. While placental transport has long been studied using simplified multiscale models, progress has been constrained by limited access to realistic microstructure geometries, uncertainty in barrier composition, and difficulties linking local geometries to organ-level measurements. Here, we review recent advances in placental imaging and mathematical modelling that are enabling better characterisation of microscale exchange. We outline how multimodal structural imaging, including X-ray phase-contrast approaches, microCT, optical microscopy and volume electron microscopy, can quantify villous and vascular architecture across scales. We discuss modelling frameworks informed by these data, including descriptions of maternal and fetal haemodynamics, image-based exchange-capacity concepts, and compartmental approaches that incorporate delivery limitations. We also discuss recent advances in the understanding of transporter-mediated transfer, and the emerging role of spatial 'omics in parametrising membrane function and regional heterogeneity. We conclude by identifying likely next steps and ways forward for image-based models of exchange in the human placenta.