Impact of ectopic calcification on vascular oxygenation in placental dysfunction models: Simultaneous in vivo assessment with multi-parametric ultrasound and photoacoustic imaging

Preeclampsia (PE) is a prevalent gestational disorder occurring in 2-10% of all pregnancies. It is associated with placental dysfunction which can result in maternal mortality and preterm birth. Despite scientific advances, the underlying mechanisms of PE and the progression of placental dysfunction remain poorly understood without preventative or curative treatment. Other than blood tests and postdelivery placental diagnostics, there are limited detection methods for monitoring placental health. A major roadblock is the lack of imaging modalities available to monitor placental hemodynamics, as the commonly used clinical imaging systems are either harmful due to ionizing sources, too expensive and inaccessible, or provide insufficient data. We propose the combination of quantitative ultrasound and photoacoustic imaging (QUSPAI) to characterize the material and structural changes of the placenta during pregnancy in normal and disease states. The Slc20a2 murine model of placental dysfunction has previously been characterized by increased ectopic placental vascular calcification, reduced fetal growth, and decreased postnatal bone mineral density. In this study we utilized the Slc20a2 model and imaged knockout (KO) and wildtype (WT) placentae on embryonic day (E)18.5. The dual-wavelength images and radio frequency data were collected in vivo and ex vivo to provide quantitative ultrasound spectral (QUS) parameters and blood oxygen saturation. The photoacoustic images indicated that the WT tissue had statistically higher blood oxygen saturation (StO2) values than the KO tissues while QUS data revealed strain-specific calcification effects. Building upon the E18.5 gestation data collected here, future work will involve monitoring longitudinal changes in these parameters, including early calcification, to support translating this method for early diagnosis of placental vascular diseases.