Physics-informed stereology for estimating placental diffusive exchange capacity

作者：Richard Mcnair, Carl A. Whitfield, Gowsihan Poologasundarampillai, Oliver E. Jensen, Igor L. Chernyavsky · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.03.04.709535 · 研究领域：Pregnancy and preeclampsia studies、Preterm Birth and Chorioamnionitis、Fetal and Pediatric Neurological Disorders

Abstract Introduction Stereological estimates of villous membrane thickness and surface area are widely used to infer the diffusive exchange capacity of the human placenta. A key geometric determinant of exchange capacity can be expressed as an effective diffusive length scale. Here we combine virtual histological sections with computational modelling in realistic villous geometries to assess the accuracy of classical stereological estimates of this diffusive length scale. Methods Two terminal villi, reconstructed from three-dimensional imaging, were digitally sectioned to generate random two-dimensional geometries containing fetal capillaries and surrounding villous tissue. For each section, we simulated steady diffusive transport between the fetal-capillary and intervillous-space boundaries to obtain a physics-based diffusive length scale as a reference case. Using the same geometries, we applied standard line–intercept stereology to measure harmonic-mean barrier thickness and boundary–length densities, from which a stereological estimate of diffusive length scale was derived. Results Across both villi, stereology systematically overestimated the diffusive length scale by approximately 15−25%, depending on villus and section. We identified sources of this discrepancy, including interface curvature and assumptions underpinning the stereological correction factors, using idealised models of villous structure. Conclusion These findings highlight the need for stereological appr...