Thanks to its non-invasive nature, X-ray phase contrast tomography is a very versatile imaging tool for biomedical studies. In contrast, histology is a well-established method, though having its limitations: it requires extensive sample preparation and it is quite time consuming. Therefore, the development of nano-imaging techniques for studying anatomic details at the cellular level is gaining more and more importance. In this article, full field transmission X-ray nanotomography is used in combination with Zernike phase contrast to image millimeter sized unstained tissue samples at high spatial resolution. The regions of interest (ROI) scans of different tissues were obtained from mouse kidney, spleen and mammalian carcinoma. Thanks to the relatively large field of view and effective pixel sizes down to 36 nm, this 3D approach enabled the visualization of the specific morphology of each tissue type without staining or complex sample preparation. As a proof of concept technique, we show that the high-quality images even permitted the 3D segmentation of multiple structures down to a sub-cellular level. Using stitching techniques, volumes larger than the field of view are accessible. This method can lead to a deeper understanding of the organs’ nano-anatomy, filling the resolution gap between histology and transmission electron microscopy.

中文翻译：

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X射线Zernike相衬断层扫描：毫米大小的小鼠器官组织直至亚细胞成分的3D ROI可视化

由于其非侵入性，X射线相衬断层扫描是用于生物医学研究的非常通用的成像工具。相比之下，组织学虽然有其局限性，但却是一种行之有效的方法：它需要大量的样品制备，并且非常耗时。因此，用于在细胞水平上研究解剖学细节的纳米成像技术的发展变得越来越重要。在本文中，全场透射X射线纳米断层扫描技术与Zernike相衬技术结合使用，可在高空间分辨率下成像毫米大小的未染色组织样本。从小鼠肾脏，脾脏和哺乳动物癌中获得不同组织的感兴趣区域（ROI）扫描。得益于相对较大的视野和有效的像素尺寸（低至36 nm），这种3D方法可以可视化每种组织类型的特定形态，而无需染色或复杂的样品制备。作为概念验证的技术，我们表明高质量图像甚至允许对多个结构进行3D分割，直至亚细胞水平。使用缝合技术，可以访问比视场大的体积。这种方法可以导致对器官的纳米解剖结构的更深入了解，填补了组织学和透射电子显微镜之间的分辨率空白。大于视野的体积是可访问的。这种方法可以导致对器官的纳米解剖结构的更深入了解，填补了组织学和透射电子显微镜之间的分辨率空白。大于视野的体积是可访问的。这种方法可以导致对器官的纳米解剖结构的更深入了解，填补了组织学和透射电子显微镜之间的分辨率空白。