Non-invasive MRI offers a powerful platform for longitudinal, quantitative assessment of the mammalian reproductive system in vivo. This presentation describes a suite of MRI methodologies developed to interrogate mouse pregnancy from embryo implantation through late gestation, and their application to mechanistic studies of vascular remodeling, placental transport, and fetoplacental physiology in normal and pathological pregnancies.

Using contrast-enhanced MRI with macromolecular probes (biotin-BSA-GdDTPA), implantation sites can be detected as early as embryonic day 4.5, with quantitative mapping demonstrating that elevated vascular permeability, rather than increased blood volume, is the earliest hemodynamic event at the implantation site, preceding the angiogenic expansion that becomes apparent at E5.5. Dynamic contrast-enhanced MRI further established that uterine dendritic cells directly regulate decidual angiogenesis, as their conditional ablation in transgenic mice caused reduced vascular expansion and attenuated vascular maturation at implantation sites. It further established the roles of hyaluronan synthesis and degradation and ECM cross linking by tissue transglutaminase in implantation-induced maternal decidua angiogenesis.

For mid-to-late gestation, diffusion-weighted MRI combined with contrast-enhanced MRI resolved the multicompartmental architecture of the mouse placenta distinguishing the freely diffusive maternal blood pool, the strongly perfused fetal vasculature, and the intermediate trophoblastic labyrinth at different gestational stages. Macromolecular DCE-MRI phenotyped maternal albumin turnover across gestation, tracking increasing maternal blood volume fraction, phagocytic contrast uptake, and enabling detection of fetal resorptions and strain differences in embryo transfer models. Bidirectional arterial spin labeling MRI exploited the dual arterial blood supply of the mouse uterine horns to uniquely identify individual fetuses in multifetal pregnancies in utero, opening possibilities for longitudinal phenotyping of transgenic and knockout models.

Beyond perfusion, we developed MRI methods to image active molecular transport across the placental barrier. A novel multimodal approach exploited the T2*-dependent signal “off-switch” triggered by transporter-mediated aggregation of biotinylated contrast agent (b-BSA-GdDTPA) to map biotin (Vitamin H) transporter activity in the murine placenta in vivo; suppression of signal by pre-saturation with free biotin confirmed specificity, and results were validated by PET, histology, and ICP-MS. DCE-MRI thus captures transporter-mediated uptake, retention, and recycling of the macromolecular probe, enabling mapping of microstructural compartmentation and transporter activity without fetal exposure to contrast media.

To probe fetoplacental oxygenation, BOLD T2* and oxygen-weighted T1 contrast mechanisms were combined under graded respiratory challenges to generate MRI-derived oxygen-hemoglobin dissociation curves and maps of fetal-placental oxygen-hemoglobin affinity noninvasively in pregnant mice at 9.4 T. Hyperpolarized ¹³C MRI extended these capabilities to real-time placental metabolic imaging: hyperpolarized urea crossed the placental barrier with fetal organ signatures detectable in the liver, while [1-¹³C]pyruvate revealed active glycolysis within the trophoblastic interface with both tracers detecting aberrant transport and reduced placental glycolysis in a preeclampsia model. Spatiotemporally encoded (SPEN) diffusion and perfusion MRI at ~150 µm in-plane resolution further resolved placental compartment-specific changes in models of preeclampsia and fetal growth restriction.

Together, these methodologies constitute multi-parametric MRI toolkit for non-invasive phenotyping of the maternal-fetal unit, with broad applicability to genetic models of reproductive pathology and to the development of early diagnostic markers for pregnancy complications.