Summary Upon implantation, mammalian embryos undergo major morphogenesis and key developmental processes such as body axis specification and gastrulation. However, limited accessibility obscures the study of these crucial processes. Here, we develop an ex vivo Matrigel-collagen-based culture to recapitulate mouse development from E4.5 to E6.0. Our system not only recapitulates embryonic growth, axis initiation, and overall 3D architecture in 49% of the cases, but its compatibility with light-sheet microscopy also enables the study of cellular dynamics through automatic cell segmentation. We find that, upon implantation, release of the increasing tension in the polar trophectoderm is necessary for its constriction and invagination. The resulting extra-embryonic ectoderm plays a key role in growth, morphogenesis, and patterning of the neighboring epiblast, which subsequently gives rise to all embryonic tissues. This 3D ex vivo system thus offers unprecedented access to peri-implantation development for in toto monitoring, measurement, and spatiotemporally controlled perturbation, revealing a mechano-chemical interplay between extra-embryonic and embryonic tissues.
We present an overview of symmetry breaking in early mammalian development as a continuous process from compaction to specification of the body axes. While earlier studies have focused on individual symmetry-breaking events, recent advances enable us to explore progressive symmetry breaking during early mammalian development. Although we primarily discuss embryonic development of the mouse, as it is the best-studied mammalian model system to date, we also highlight the shared and distinct aspects between different mammalian species. Finally, we discuss how insights gained from studying mammalian development can be generalized in light of self-organization principles. With this review, we hope to highlight new perspectives in studying symmetry breaking and self-organization in multicellular systems.
Objectives: To evaluate the performance of readout-segmented echo-planar imaging DWI (rs-EPI DWI) in detecting and characterizing breast cancers in a large Chinese cohort with comparison to dynamic contrast-enhanced MRI (DCE-MRI).Methods: The institutional review board approved this retrospective study with waived written informed consent. A total of 520 women (mean age, 43.1- ± 10.5-years) were included from July 2013 to October 2019. First, the ability of rs-EPI DWI in detecting breast lesions identified by DCE-MRI was evaluated. The lesion conspicuity of rs-EPI-DWI and DCE-MRI was compared using the Wilcoxon signed rank test. With pathology as a reference, the performance of rs-EPI DWI and DCE-MRI in distinguishing breast cancers was evaluated and compared using the Chi-square test.Results: Of 520 women, 327/520 (62.9%) patients had 423 lesions confirmed by pathology with 203 benign and 220 malignant lesions. The rs-EPI DWI can detect 90.8% (659/726) (reader 1) and 90.6% (663/732) (reader 2) of lesions identified by DCE-MRI. The lesion visibility was superior for DCE-MRI than rs-EPI-DWI (all p < 0.05). With pathology as a reference, the sensitivities and specificities of rs-EPI DWI in diagnosing breast cancers were 95.9% (211/220) and 85.7% (174/203) for reader 1 and 97.7% (215/220) and 86.2% (175/203) for reader 2. No significant differences were found for the performance of DCE-MRI and rs-EPI DWI in discriminating breast cancers (all p > 0.05).Conclusions: Although with an inferior lesion visibility, rs-EPI DWI can detect about 90% of breast lesions identified by DCE-MRI and has comparable diagnostic capacity to that of DCE-MRI in identifying breast cancer.
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