Computational 3d histological phenotyping of whole zebrafish by x-ray histotomography

Yifu Ding, Daniel J. Vanselow, Maksim A. Yakovlev, Spencer R. Katz, Alex Y. Lin, Darin P. Clark, Phillip Vargas, Xuying Xin, Jean E. Copper, Victor A. Canfield, Khai C. Ang, Yuxin Wang, Xianghui Xiao, Francesco De Carlo, Damian B.Van Rossum, Patrick La Riviere, Keith C. Cheng

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


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. 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. Striking individual phenotypic variation was apparent from color maps of computed densities of brain nuclei. Unlike histology, the histotomography also allows the study of 3-dimensional structures of millimeter scale that cross multiple tissue planes. 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.

Original languageEnglish (US)
Article numbere44898
StatePublished - May 2019

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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