Organismal phenotypes frequently involve multiple organ systems. Histology is a powerful way to detect cellular and tissue phenotypes but is largely descriptive and subjective. Synchrotron-based X-ray micro-tomography (micro-CT) can yield 3-dimensional whole-organism images suitable for quantitative histological phenotyping. Whole zebrafish, a small vertebrate model, were scanned at ~1-micron voxel resolutions. Using micro-CT optimized for cellular characterization (histotomography), brain nuclei were computationally segmented and assigned to brain regions. Shape and volume were computed for populations of nuclei such as those of motor neurons and red blood cells. Striking individual phenotypic variation was apparent from color maps of computed cell density. Unlike histology, histotomography allows the detection of phenotypes that require millimeter scale context in multiple planes.

