Modeling Normal Mouse Uterine Contraction and Placental Perfusion with Non-invasive Longitudinal Dynamic Contrast Enhancement MRI.

The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual's entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities. Non-invasive imaging that can longitudinally probe murine placental health in vivo are critical to understanding placental development throughout pregnancy. We developed advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development. We developed a dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) pipeline combined with advanced image process methods to model uterine contraction and placental perfusion dynamics. Our novel imaging pipeline uses subcutaneous administration of gadolinium for steepest-slope based perfusion evaluation. This enables non-invasive longitudinal monitoring. Additionally, we advance the placental perfusion chamber paradigm with a novel physiologically-based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and continuing remodeling throughout gestation. Lastly, using optic flow to quantify placental motions arisen from uterine contractions in conjunction with time-frequency analysis, we demonstrated that the placenta exhibited asymmetric contractile motion.

Modeling normal mouse uterine contraction and placental perfusion with non-invasive longitudinal dynamic contrast enhancement MRI.

BACKGROUND: The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual's entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities. OBJECTIVE: Our goal is to create a non-invasive preclinical imaging pipeline that can longitudinally probe murine placental health in vivo. We use advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development. METHODOLOGY: We implement dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and analysis pipeline to quantify uterine contraction and placental perfusion dynamics. We use optic flow and time-frequency analysis to quantify and characterize contraction-related placental motion. Our novel imaging and analysis pipeline uses subcutaneous administration of gadolinium for steepest slope-based perfusion evaluation, enabling non-invasive longitudinal monitoring. RESULTS: We demonstrate that the placenta exhibits spatially asymmetric contractile motion that develops from E14.5 to E17.5. Additionally, we see that placental perfusion, perfusion delivery rate, and substrate delivery all increase from E14.5 to E17.5, with the High Perfusion Chamber (HPC) leading the placental changes that occur from E14.5 to E17.5. DISCUSSION: We advance the placental perfusion chamber paradigm with a novel, physiologically based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and remodeling throughout gestation. CONCLUSION: Our pipeline enables the non-invasive, longitudinal assessment of multiple placenta functions from a single imaging session. Our pipeline serves as a key toolbox for advancing research in mouse models of placental disease and disorder.

Pre-pregnancy stress induces maternal vascular dysfunction during pregnancy and postpartum.

An estimated 20% of women suffer from a stress-related mood disorder including depression and anxiety during and after pregnancy, making these disorders among the most common complications of pregnancy. These stress-related disorders are associated with adverse pregnancy outcomes including gestational hypertension and preeclampsia, which are associated with poor cardiometabolic health postpartum. Despite these associations, the direct impact of stress and related disorders on maternal vascular health, and contributing mechanisms, remain understudied. The aim of this study was to investigate the effect of pre-pregnancy stress on maternal vascular outcomes in a BALB/c mouse model of chronic unpredictable stress. Maternal blood pressure and ex-vivo vascular function were investigated during pregnancy and postpartum. Offspring characteristics were assessed at the end of pregnancy and postpartum. Main findings show that pre-pregnancy stress exposure increased blood pressure during mid and late pregnancy and impaired ex vivo vascular function at the end of pregnancy. These effects persisted into the postpartum period, suggesting a long-term effect of stress on maternal vascular health, which appear to be partially attributable to disruptions in nitric oxide (NO) pathway signaling. These data suggest exposure to stress and related disorders, even prior to pregnancy, can contribute to vascular complications during pregnancy and postpartum.