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Organismal phenotypes frequently involve multiple organ systems. Histology
is a powerful way to detect cellular and tissue phenotypes, but is largely
descriptive and subjective. 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. Using micro-CT optimized for cellular characterization
(histo-tomography), brain nuclei can be computationally segmented and
assigned to brain regions. Shape and volume can be computed for
populations of nuclei, motor neurons and red blood cells. Computed cell
density revealed striking individual phenotypic variation. Unlike
histology, histo-tomography allows the detection of phenotypes that
require millimeter scale context in multiple planes. We expect the
computational and visual insights into 3D tissue architecture provided by
histo-tomography to be useful for reference atlases, hypothesis
generation, comprehensive organismal screens, and diagnostics.
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