Histology’s dependence upon such thin slices makes it impossible to see the entirety of cells and structures that are thicker than the slice, or to accurately measure three-dimensional features such as shape or volume. To allow individual cells to be distinguished, tissues are cut into slices less than 1/20th of a millimeter thick. But despite its frequent use, histology comes with limitations. This powerful technique has revolutionized biology and medicine.

A common way of studying these microscopic cell changes is by an approach called histology: thin slices of centimeter-sized samples of tissues are taken from patients, stained to distinguish cellular components, and examined for abnormal features. We expect the computational and visual insights into 3D cell and tissue architecture provided by histotomography to be useful for reference atlases, hypothesis generation, comprehensive organismal screens, and diagnostics.ĭiagnosing diseases, such as cancer, requires scientists and doctors to understand how cells respond to different medical conditions. Unlike histology, the histotomography also allows the study of 3-dimensional structures of millimeter scale that cross multiple tissue planes. Striking individual phenotypic variation was apparent from color maps of computed densities of brain nuclei. Micro-CT optimized for cellular characterization (histotomography) allows brain nuclei to be computationally segmented and assigned to brain regions, and cell shapes and volumes to be computed for motor neurons and red blood cells. To determine how synchrotron-based X-ray micro-tomography (micro-CT) can yield 3-dimensional whole-organism images suitable for quantitative histological phenotyping, we scanned whole zebrafish, a small vertebrate model with diverse tissues, at ~1 micron voxel resolutions. Histology is a powerful way to detect cellular and tissue phenotypes, but is largely descriptive and subjective. Organismal phenotypes frequently involve multiple organ systems.

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