Mammalian models, and mouse studies in particular, play a central role in our understanding of placental development. Magnetic resonance imaging (MRI) could be a valuable tool to further these studies, providing both structural and functional information. As fluid dynamics throughout the placenta are driven by a variety of flow and diffusion processes, diffusion-weighted MRI could enhance our understanding of the exchange properties of maternal and fetal blood pools-and thereby of placental function. These studies, however, have so far been hindered by the small sizes, the unavoidable motions, and the challenging air/water/fat heterogeneities, associated with mouse placental environments. The present study demonstrates that emerging methods based on the spatiotemporal encoding (SPEN) of the MRI information can robustly overcome these obstacles. Using SPEN MRI in combination with albumin-based contrast agents, we analyzed the diffusion behavior of developing placentas in a cohort of mice. These studies successfully discriminated the maternal from the fetal blood flows; the two orders of magnitude differences measured in these fluids' apparent diffusion coefficients suggest a nearly free diffusion behavior for the former and a strong flow-based component for the latter. An intermediate behavior was observed by these methods for a third compartment that, based on maternal albumin endocytosis, was associated with trophoblastic cells in the interphase labyrinth. Structural features associated with these dynamic measurements were consistent with independent intravital and ex vivo fluorescence microscopy studies and are discussed within the context of the anatomy of developing mouse placentas.robust diffusion MRI | high-field placental MRI | placental ADC maps | multimodal imaging

The placenta performs a wide range of physiological functions; insufficiencies in these functions may result in a variety of severe prenatal and postnatal syndromes with long-term negative impacts on human adult health. Recent advances in magnetic resonance imaging (MRI) studies of placental function, in both animal models and humans, have contributed significantly to our understanding of placental structure, blood flow, oxygenation status, and metabolic profile, and have provided important insights into pregnancy complications.

Tumors emerge as a result of sequential acquisition of genetic, epigenetic, and somatic alterations promoting cell proliferation and survival. The maintenance and expansion of tumor cells relies on their ability to adapt to changes in their microenvironment, along with acquisition of the ability to remodel their surroundings. Tumor cells interact with two types of interconnected microenvironments, the metabolic cell autonomous microenvironment and the non-autonomous cellular-molecular microenvironment comprising interactions between tumor cells and the surrounding stroma. Hypoxia is a central player in cancer progression, affecting not only tumor cell autonomous functions such as cell division and invasion, resistance to therapy and genetic instability, but also non-autonomous processes such as angiogenesis, lymphangiogenesis and inflammation, all contributing to metastasis. Closely related microenvironmental stressors, affecting cancer progression include in addition to hypoxia, also elevated interstitial pressure and oxidative stress. Non invasive imaging offers multiple means for monitoring the tumor microenvironment and its consequences, and can thus assist in understanding the biological basis of hypoxia and microenvironmental stress in cancer progression, and in development of strategies for monitoring therapies targeted at stress induced tumor progression.

The authors of this study present a noninvasive approach for obtaining MR imaging–based oxygen-hemoglobin dissociation curves and for deriving oxygen tension values at which hemoglobin is 50% saturated and maps for the placenta and fetus in pregnant mice.

Noninvasive imaging is a critical part of the study of developing embryos/fetuses, particularly in the context of alterations of gene expression in genetically modified animals. However, in litter-bearing animals, such as mice, the inability to accurately identify individual embryo/fetus in utero is a major obstacle to longitudinal, noninvasive in vivo studies. Arterial spin labeling MRI was adopted here to determine the fetal order along the uterine horns in vivo, based on the specific pattern of dual arterial blood supply within the mouse uterine horns. Blood enters the mouse uterus cranially through the ovarian artery and caudally through the uterine artery. Saturation slices were alternately placed on the maternal heart or on the bifurcation point of the common iliac artery, thereby saturating either downward inflow via the ovarian arteries or upward inflow via the uterine arteries, respectively. Saturation maps provided a unique signature with highly significant correlation between the direction-dependent magnetization transfer and the position of the fetuses/placentas along the uterine horns. The bidirectional arterial spin labeling-MRI method reported here opens possibilities to determine and pursue phenotypic alterations in fetuses and placentas in longitudinal studies of transgenic and knockout mice models, and for studying defects in placental vascular architecture. Magn Reson Med 68:560-570,