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Stanic, A. K.

Publications and source records attributed to Stanic, A. K..

2 recordsLinked to original sources
bioRxiv2026

Ferumoxytol dynamic contrast-enhanced MRI for in vivo longitudinal cotyledon perfusion assessment with pathology correlation in a rhesus macaque thrombotic injury model

IntroductionWhile placental perfusion and pathology jointly affect pregnancy outcomes, cotyledon-specific perfusion across gestation and its correlation with local injury is not yet well understood. Ferumoxytol dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a promising way to noninvasively identify cotyledons across gestation and quantify longitudinal cotyledon-specific perfusion changes. Additionally, intraplacental injection of bioactive fibrin sealant allows us to model thrombotic placental injury and further assess cotyledon-level relationships between perfusion and significant injury. MethodsPregnant rhesus macaques (N=13) received intrauterine saline or fibrin sealant injections at gestational day (GD) [~]101 and underwent ferumoxytol DCE-MRI at GDs [~]100, 115, and 145. Placental perfusion domains derived from contrast arrival time were segmented at each imaging time point and matched to cotyledons identified following tissue collection by cesarean section, with cotyledon perfusion quantified longitudinally and correlated with cotyledon-specific quantitative histopathology. ResultsAll pregnancies were successfully carried to term. Fibrin sealant injections induced significantly higher levels of placental pathology compared to saline controls. MRI-derived perfusion domains were largely consistent across gestation and showed predominantly one-to-one correspondence with term cotyledons, with successful perfusion-pathology pairing achieved in 153 cotyledons. Longitudinal cotyledon perfusion changes showed significant positive correlations with villous agglutination injuries. ConclusionsFeasibility of noninvasively tracking placental cotyledon perfusion using ferumoxytol DCE-MRI was demonstrated, and the efficacy of the rhesus macaque thrombotic injury model was confirmed. The positive perfusion-pathology correlations suggested intrinsic placental regulatory mechanisms and functional plasticity. This new framework is promising for future translational studies and validation of ex vivo cotyledon perfusion models. HighlightsO_LILongitudinal tracking of placental perfusion domains with ferumoxytol MRI C_LIO_LISuccessful matching of cotyledons and MRI-derived perfusion domains C_LIO_LIConfirmed thrombotic injury-model induced cotyledon pathology C_LIO_LIMaternal perfusion compensation in presence of villous pathology C_LI

pathology↗
bioRxiv2026

Bridging Cotyledon Pathology and Perfusion in Healthy Primate Pregnancy

IntroductionHealthy and diseased placentae alike often display some degree of pathology. However, quantitative techniques to characterize common pathologies and their relationship to local maternal hemodynamics in healthy primate placentae are currently limited. MethodsPlacentae from seven rhesus macaques were imaged by MRI at three time points across mid-to late-gestation, to quantify placental blood volume, flow, and perfusion from maternal spiral arteries across pregnancy. Near term, we collected placental cotyledons, digitized hematoxylin/eosin-stained slides, then segmented and annotated sub-tissues and major pathologies (intervillous gaps, fibrin deposition, villous agglutination, inflammatory agglutination, and stromal mineralization) within each cotyledon. Individual pathologies were assessed in relation to each other and MRI perfusion metrics, in a cotyledon-specific manner. Parallel analyses were performed to investigate both basic (Spearman correlation) and animal variance-negated (dimensionality-reduction) relationships. ResultsCotyledons with increased stromal mineralization demonstrated low blood perfusion across pregnancy, alongside significant compensatory changes. Mineralization was further associated with decreased fetal weight, across all sub-tissues. Dimensionality reduction revealed maternal vascular malperfusion-associated pathologies as the largest contributor to dataset variance. Additionally, pathologies commonly associated with healthy placental function demonstrated low cotyledon blood flow and volume at all timepoints, with no evidence of compensatory changes across gestation. ConclusionsComprehensive digital annotation revealed several relationships connecting pathology and maternal blood perfusion in the healthy primate pregnancy, at the smallest functional unit of the placenta. This methodological framework embeds pathologist-refined morphological expertise into a quantitative, spatially resolved format that can ground, rather than be replaced by, unsupervised computational approaches to placental analysis.

pathology↗