Microscopic Computed Tomography-Based Virtual Histology of Embryos

Advances in imaging technologies and computational capabilities have made possible novel methods for phenotypic assessments and visualization of detailed anatomical structures of whole embryos. We recently reported a rapid and inexpensive technique for achieving high-resolution virtual histology for phenotyping assessment of mouse embryos (Johnson et al., PLoS Genet 2:e61, 2006). By en bloc staining in a solution of electron-dense osmium tetroxide followed by volumetric X-ray computed tomography, whole embryos can be imaged at isometric resolutions as high as 2.5 μm, depending on the size of the specimen. The datasets generated by these techniques are compatible with state-of-the-art computational methods of organ pattern analysis. This method of Microscopic Computed Tomography (microCT)-based Virtual Histology of embryos allows one to rapidly and accurately phenotype transgenic embryos or to engage in developmental and reproductive toxicology studies of investigational drugs at better resolution, less time, and less expense than traditional histology, magnetic resonance microscopy, or the classical Wilson and Staples procedures.