RT Journal Article SR Electronic T1 Three-Dimensional Histology of Whole Zebrafish by Sub-Micron Synchrotron X-ray Micro-Tomography JF bioRxiv FD Cold Spring Harbor Laboratory SP 392381 DO 10.1101/392381 A1 Yifu Ding A1 Daniel J. Vanselow A1 Maksim A. Yakovlev A1 Spencer R. Katz A1 Alex Y. Lin A1 Darin P. Clark A1 Phillip Vargas A1 Xuying Xin A1 Jean E. Copper A1 Victor A. Canfield A1 Khai C. Ang A1 Yuxin Wang A1 Xianghui Xiao A1 Francesco De Carlo A1 Damian B. van Rossum A1 Patrick La Rivière A1 Keith C. Cheng YR 2018 UL http://biorxiv.org/content/early/2018/08/25/392381.abstract AB Histological studies providing cellular insights into tissue architecture have been central to biological discovery and remain clinically invaluable today. Extending histology to three dimensions would be transformational for research and diagnostics. However, three-dimensional histology is impractical using current techniques. We have customized sample preparation, synchrotron X-ray tomographic parameters, and three-dimensional image analysis to allow for complete histological phenotyping using whole larval and juvenile zebrafish. The resulting digital zebrafish can be virtually sectioned and visualized in any plane. Whole-animal reconstructions at subcellular resolution also enable computational characterization of the zebrafish nervous system by region-specific detection of cell nuclei and quantitative assessment of individual phenotypic variation. Three-dimensional histological phenotyping has potential use in genetic and chemical screens, and in clinical and toxicological tissue diagnostics.One Sentence Summary Synchrotron X-ray micro-tomography can be used to rapidly create 3-dimensional images of fixed and stained specimens without sectioning, enabling computational histological phenotyping at cellular resolution.Abbreviations3Dthree-dimensionalH&Ehematoxylin & eosin2Dtwo-dimensionalmicro-CTX-ray micro-tomographydpfdays post-fertilizationPTAphosphotungstic acidRBCred blood cell