Virtual histology of an 11.5-day-old mouse embryo at 6 micron resolution. The microCT scans, shown in grayscale, correlate precisely with actual histological specimens of the same embryo. Using microCT-based virtual histology as a screen, features of interest can later be explored by light microscopy, as shown in the serial zooming of the emerging nerve roots in the trigeminal ganglia, the cells of origin of most of the sensory fibers of the trigeminal nerve, which is responsible for sensory enervation of the face and motor enervation to muscles for chewing.

Using traditional dissection methods to analyze tissue samples, histologists must laboriously slice a sample of tissue—for example, a mutant-mouse embryo—into a thousand sections. Then they must scrutinize each one under a microscope for telltale anatomical clues to genetic malfunction.

A new technique, however, promises to come to the aid of tired-eyed histologists everywhere. Called virtual histology, the technique uses X-ray microscopic computed tomography (microCT) to generate an easy-to-manipulate computer file of 3-D images of the sample tissue.

Virtual histology involves first staining the sample with osmium tetroxide—a chemical that differentially stains organs and soft tissues, making them more clearly visible under X-ray. The tissue is then scanned using microCT, and the resulting 3-D images, with a resolution of up to 6 microns (or about one-tenth the diameter of a human hair), can be examined in detail for abnormalities.

Image: Courtesy of Charles Keller

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