In-utero 3D MRI analysis of embryos in mice is difficult due to the periodic and non-periodic motion, small tissues and multiple embryos involved. This paper presents an automated algorithm for serial alignment of fetal tissue in MRI of pregnant mice. The algorithm extends our former algorithm to allow follow up across time between 3D MR sequences in a difficult novel small animal application. The algorithm is based on features combining intensity and geometric information and the registration energy function is minimized by alternating optimization with regard to the feature correspondence and transformation model. Experimental validation on a set of MRI acquisition with fetal livers and placentas demonstrate the high accuracy and promise of the approach. The results confirm that measures of development can be automatically derived from multifetal pregnancy in mice.
Ovarian tissue cryopreservation and transplantation is one of a few available treatments for fertility preservation in women diagnosed with cancer. Rapid revascularization is essential for reducing hypoxic damage after grafting and protecting the primordial follicles reserve. Using a mouse model of heterotopic ovarian graft transplantation, we have delineated the role of endothelial Akt1 expression using longitudinal magnetic resonance imaging follow-up to quantify angiogenic response. Endothelial Akt1 activation in ovarian grafts promoted angiogenesis to support the graft during posttransplantation hypoxic period. Similarly, simvastatin therapy activated Akt1 at the transplantation site and improved the revascularization and vascular support of ovarian grafts. These results serve as an important first step toward pharmacological intervention to improve revascularization of ovarian grafts and restoration of fertility in cancer survivors. The pro-angiogenic effects reported here may extend beyond improving ovarian graft reception in fertility preservation and could potentially be used for different organ or tissue transplantation.
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.
Significance Fluid motion measurements can provide valuable insight regarding the structure and function of developing placentas. This study presents to our knowledge the first MRI characterization of multicompartmental diffusion and incoherent flow in pregnant mice at different gestation stages, made possible by methods herein introduced for the single-scan acquisition of diffusion-encoded images in the challenging environment associated with in vivo embryonic studies. These methods were combined with a customized contrast agent to reveal a freely diffusive maternal blood pool, a strongly perfused fetal blood flow, and an intermediate behavior for the trophoblastic labyrinth cell layer. Structural features associated with these dynamics were corroborated with ex vivo fluorescence microscopy and are discussed within the context of the anatomical structure of developing mouse placentas.
In mammalians pregnancy, proper adaptations of the maternal vasculature and cardiac function are essential in order fulfill the requirements of the growing fetus(es). These adaptations are particularly demanding for mammals bearing large-litter pregnancies, in which there is an inherent conflict between the interests of the individual fetus and the welfare of the entire progeny. Previous studies reported that in mice, maternal blood flow to the placentas occurs via an arterial uterine loop generated by arterial-arterial anastomosis of the uterine artery and the uterine branch of the ovarian artery, resulting in counter bi-directional flow. The aim of this study was to revisit the maternal adaptation to large litter pregnancies. Pregnant mice at late gestation (Embryonic day 17.5; ICR mice, n=11 mothers, 86 placentas/fetuses; PKBa/Akt1+/- mice, n=17 mothers, 128 fetuses/placentas) were examined through advanced in vivo Magnetic Resonance Imaging (MRI) and fluorescence imaging. In contrast to previous reports we demonstrate that each placenta is supplied by two distinct arterial inputs stemming from the uterine artery and from the uterine branch of the ovarian artery, with position dependent distribution of flow from each source. Maternal blood flow to the placentas was dependent on litter size and was attenuated for placentas located centrally along the uterine horn. Distinctive apposing, inter-fetal effects of either reduced or elevated maternal blood flow, were measured for placenta of normal fetuses that are positioned adjacent to either pathological, or to hypovascular Akt1-deficient placentas, respectively. We demonstrate unique features of the maternal uterine vasculature, which provide robustness and plasticity, essential for sustaining large-litter pregnancies and overcoming pathologic challenges. Remarkably, the dual arterial supply is conserved also in mammals bearing a single offspring, including humans.
