Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
Abstract
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.
- Authors:
-
- Penn State College of Medicine, Hershey, PA (United States)
- Duke Univ., Durham, NC (United States)
- The Univ. of Chicago, Chicago, IL (United States)
- Omnivision Technologies, Inc., Santa Clara, CA (United States)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Argonne National Lab. (ANL), Lemont, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1558992
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Volume: 8; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Ding, Yifu, Vanselow, Daniel J., Yakovlev, Maksim A., Katz, Spencer R., Lin, Alex Y., Clark, Darin P., Vargas, Phillip, Xin, Xuying, Copper, Jean E., Canfield, Victor A., Ang, Khai C., Wang, Yuxin, Xiao, Xianghui, De Carlo, Francesco, van Rossum, Damian B., La Riviere, Patrick, and Cheng, Keith C. Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography. United States: N. p., 2019.
Web. doi:10.7554/eLife.44898.
Ding, Yifu, Vanselow, Daniel J., Yakovlev, Maksim A., Katz, Spencer R., Lin, Alex Y., Clark, Darin P., Vargas, Phillip, Xin, Xuying, Copper, Jean E., Canfield, Victor A., Ang, Khai C., Wang, Yuxin, Xiao, Xianghui, De Carlo, Francesco, van Rossum, Damian B., La Riviere, Patrick, & Cheng, Keith C. Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography. United States. https://doi.org/10.7554/eLife.44898
Ding, Yifu, Vanselow, Daniel J., Yakovlev, Maksim A., Katz, Spencer R., Lin, Alex Y., Clark, Darin P., Vargas, Phillip, Xin, Xuying, Copper, Jean E., Canfield, Victor A., Ang, Khai C., Wang, Yuxin, Xiao, Xianghui, De Carlo, Francesco, van Rossum, Damian B., La Riviere, Patrick, and Cheng, Keith C. Tue .
"Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography". United States. https://doi.org/10.7554/eLife.44898. https://www.osti.gov/servlets/purl/1558992.
@article{osti_1558992,
title = {Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography},
author = {Ding, Yifu and Vanselow, Daniel J. and Yakovlev, Maksim A. and Katz, Spencer R. and Lin, Alex Y. and Clark, Darin P. and Vargas, Phillip and Xin, Xuying and Copper, Jean E. and Canfield, Victor A. and Ang, Khai C. and Wang, Yuxin and Xiao, Xianghui and De Carlo, Francesco and van Rossum, Damian B. and La Riviere, Patrick and Cheng, Keith C.},
abstractNote = {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.},
doi = {10.7554/eLife.44898},
journal = {eLife},
number = ,
volume = 8,
place = {United States},
year = {Tue May 07 00:00:00 EDT 2019},
month = {Tue May 07 00:00:00 EDT 2019}
}
Web of Science
Works referenced in this record:
Structure and Function of Skeletal Muscle in Zebrafish Early Larvae
journal, April 2008
- Dou, Ying; Andersson-Lendahl, Monika; Arner, Anders
- The Journal of General Physiology, Vol. 131, Issue 5
The Knockout Mouse Project
text, January 2004
- Libraries, The University of North Carolina at Chapel Hill University
- The University of North Carolina at Chapel Hill University Libraries
Three-dimensional microCT imaging of mouse development from early post-implantation to early postnatal stages
journal, November 2016
- Hsu, Chih-Wei; Wong, Leeyean; Rasmussen, Tara L.
- Developmental Biology, Vol. 419, Issue 2
Erratum: ViBE-Z: a framework for 3D virtual colocalization analysis in zebrafish larval brains
journal, September 2012
- Ronneberger, Olaf; Liu, Kun; Rath, Meta
- Nature Methods, Vol. 9, Issue 10
3D reconstruction of histological sections: Application to mammary gland tissue
journal, March 2010
- Arganda-Carreras, Ignacio; Fernández-González, Rodrigo; Muñoz-Barrutia, Arrate
- Microscopy Research and Technique, Vol. 73, Issue 11
Contrast-Enhanced X-Ray Micro-Computed Tomography as a Versatile Method for Anatomical Studies of Adult Zebrafish
journal, August 2016
- Babaei, Fatemeh; Hong, Tony Liu Chi; Yeung, Kelvin
- Zebrafish, Vol. 13, Issue 4
The Human Cell Atlas
journal, December 2017
- Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.
- eLife, Vol. 6
MicroCT for molecular imaging: Quantitative visualization of complete three-dimensional distributions of gene products in embryonic limbs
journal, September 2011
- Metscher, Brian D.; Müller, Gerd B.
- Developmental Dynamics, Vol. 240, Issue 10
Three-dimensional network of Drosophila brain hemisphere
journal, November 2013
- Mizutani, Ryuta; Saiga, Rino; Takeuchi, Akihisa
- Journal of Structural Biology, Vol. 184, Issue 2
Technique: Imaging Earliest Tooth Development in 3D Using a Silver-Based Tissue Contrast Agent: Imaging Intact Embryonic Teeth in 3D
journal, December 2013
- Raj, Muhammad T.; Prusinkiewicz, Martin; Cooper, David M. L.
- The Anatomical Record, Vol. 297, Issue 2
Whole-Body Imaging of a Hypercholesterolemic Female Zebrafish by Using Synchrotron X-Ray Micro-CT
journal, February 2015
- Seo, Eunseok; Lim, Jae-Hong; Seo, Seung Jun
- Zebrafish, Vol. 12, Issue 1
X-ray phase-contrast in vivo microtomography probes new aspects of Xenopus gastrulation
journal, May 2013
- Moosmann, Julian; Ershov, Alexey; Altapova, Venera
- Nature, Vol. 497, Issue 7449
High-throughput discovery of novel developmental phenotypes
journal, September 2016
- Dickinson, Mary E.; Flenniken, Ann M.; Ji, Xiao
- Nature, Vol. 537, Issue 7621
The zebrafish reference genome sequence and its relationship to the human genome
journal, April 2013
- Howe, Kerstin; Clark, Matthew D.; Torroja, Carlos F.
- Nature, Vol. 496, Issue 7446
Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain
journal, March 2018
- Raj, Bushra; Wagner, Daniel E.; McKenna, Aaron
- Nature Biotechnology, Vol. 36, Issue 5
Quantitative morphometric analysis of adult teleost fish by X-ray computed tomography
text, January 2018
- Weinhardt, Venera; Shkarin, Roman; Wernet, Tobias
- Karlsruhe
MicroCT for molecular imaging: Quantitative visualization of complete three-dimensional distributions of gene products in embryonic limbs
journal, November 2011
- Metscher, Brian D.; Müller, Gerd B.
- Developmental Dynamics, Vol. 240, Issue 12
Whole-brain serial-section electron microscopy in larval zebrafish
journal, May 2017
- Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel
- Nature, Vol. 545, Issue 7654
MicroCT for comparative morphology: simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues
journal, January 2009
- Metscher, Brian D.
- BMC Physiology, Vol. 9, Issue 1
Single-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate
journal, January 2021
- Li, Pengyang; Nanes Sarfati, Dania; Xue, Yuan
- Nature Communications, Vol. 12, Issue 1
Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography
text, January 2018
- Töpperwien, Mareike; Van Der Meer, Franziska; Stadelmann, Christine
- Deutsches Elektronen-Synchrotron, DESY, Hamburg
Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain
journal, August 2011
- Hama, Hiroshi; Kurokawa, Hiroshi; Kawano, Hiroyuki
- Nature Neuroscience, Vol. 14, Issue 11
Fine structural and cytochemical analysis of the staining of synaptic junctions with phosphotungstic acid
journal, March 1968
- Bloom, Floyd E.; Aghajanian, George K.
- Journal of Ultrastructure Research, Vol. 22, Issue 5-6
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad Digital Repository
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad Digital Repository
Ultrastructural Mapping of the Zebrafish Gastrointestinal System as a Basis for Experimental Drug Studies
journal, January 2016
- Cheng, Delfine; Shami, Gerald J.; Morsch, Marco
- BioMed Research International, Vol. 2016
Submicron Imaging of Soft-Tissues Using Low-Dose Phase-Contrast X-Ray Synchrotron Microtomography With an Iodine Contrast Agent: Letter to the Editor
journal, July 2014
- Khonsari, R. H.; Healy, C.; Ohazama, A.
- The Anatomical Record, Vol. 297, Issue 10
Ex vivo characterization of articular cartilage and bone lesions in a rabbit ACL transection model of osteoarthritis using MRI and micro-CT
journal, December 2004
- Batiste, Danika L.; Kirkley, Alexandra; Laverty, Sheila
- Osteoarthritis and Cartilage, Vol. 12, Issue 12
Parasitoid biology preserved in mineralized fossils
journal, August 2018
- van de Kamp, Thomas; Schwermann, Achim H.; dos Santos Rolo, Tomy
- Nature Communications, Vol. 9, Issue 1
MicroCT for developmental biology: A versatile tool for high-contrast 3D imaging at histological resolutions
journal, March 2009
- Metscher, Brian D.
- Developmental Dynamics, Vol. 238, Issue 3
The Human Cell Atlas: from vision to reality
journal, October 2017
- Rozenblatt-Rosen, Orit; Stubbington, Michael J. T.; Regev, Aviv
- Nature, Vol. 550, Issue 7677
The Human Cell Atlas
text, January 2017
- Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.
- eLife Sciences Publications Ltd.
Parasitoid biology preserved in mineralized fossils
text, January 2018
- Van De Kamp, Thomas; Schwermann, Achim H.; Dos Santos Rolo, Tomy
- Karlsruhe
Plant Tissues in 3D via X-Ray Tomography: Simple Contrasting Methods Allow High Resolution Imaging
journal, September 2013
- Staedler, Yannick M.; Masson, David; Schönenberger, Jürg
- PLoS ONE, Vol. 8, Issue 9
Brain-wide Organization of Neuronal Activity and Convergent Sensorimotor Transformations in Larval Zebrafish
journal, November 2018
- Chen, Xiuye; Mu, Yu; Hu, Yu
- Neuron, Vol. 100, Issue 4
Whole-animal imaging, gene function, and the Zebrafish Phenome Project
journal, October 2011
- Cheng, Keith C.; Xin, Xuying; Clark, Darin P.
- Current Opinion in Genetics & Development, Vol. 21, Issue 5
In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level
journal, October 2018
- McDole, Katie; Guignard, Léo; Amat, Fernando
- Cell, Vol. 175, Issue 3
User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability
journal, July 2006
- Yushkevich, Paul A.; Piven, Joseph; Hazlett, Heather Cody
- NeuroImage, Vol. 31, Issue 3
Optimizing synchrotron microCT for high-throughput phenotyping of zebrafish
conference, August 2010
- La Rivière, Patrick J.; Clark, Darin; Rojek, Alexandra
- SPIE Optical Engineering + Applications, SPIE Proceedings
X-ray energy optimisation in computed microtomography
journal, June 1989
- Spanne, P.
- Physics in Medicine and Biology, Vol. 34, Issue 6
Essentials of Anatomic Pathology
journal, November 2006
- McGregor, A.; Dunk, L.
- Histopathology, Vol. 49, Issue 5
Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography
journal, June 2018
- Töpperwien, Mareike; van der Meer, Franziska; Stadelmann, Christine
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 27
Quantitative morphometric analysis of adult teleost fish by X-ray computed tomography
journal, November 2018
- Weinhardt, Venera; Shkarin, Roman; Wernet, Tobias
- Scientific Reports, Vol. 8, Issue 1
Ribbon scanning confocal for high-speed high-resolution volume imaging of brain
journal, July 2017
- Watson, Alan M.; Rose, Annika H.; Gibson, Gregory A.
- PLOS ONE, Vol. 12, Issue 7
Stages of embryonic development of the zebrafish
journal, July 1995
- Kimmel, Charles B.; Ballard, William W.; Kimmel, Seth R.
- Developmental Dynamics, Vol. 203, Issue 3
Chunkflow: hybrid cloud processing of large 3D images by convolutional nets
journal, March 2021
- Wu, Jingpeng; Silversmith, William M.; Lee, Kisuk
- Nature Methods, Vol. 18, Issue 4
A large-scale zebrafish gene knockout resource for the genome-wide study of gene function
journal, February 2013
- Varshney, G. K.; Lu, J.; Gildea, D. E.
- Genome Research, Vol. 23, Issue 4
Stripe and ring artifact removal with combined wavelet--Fourier filtering
text, January 2009
- Münch, B.; Trtik, P.; Marone, F.
- Optical Society of America (OSA)
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad
In vivo myosin step-size from zebrafish skeletal muscle
journal, May 2016
- Burghardt, Thomas P.; Ajtai, Katalin; Sun, Xiaojing
- Open Biology, Vol. 6, Issue 5
Three-dimensional virtual histology enabled through cytoplasm-specific X-ray stain for microscopic and nanoscopic computed tomography
journal, February 2018
- Busse, Madleen; Müller, Mark; Kimm, Melanie A.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 10
Histology-based screen for zebrafish mutants with abnormal cell differentiation
journal, October 2003
- Mohideen, Manzoor-Ali P. K.; Beckwith, Lee G.; Tsao-Wu, Gladys S.
- Developmental Dynamics, Vol. 228, Issue 3
Stripe and ring artifact removal with combined wavelet—Fourier filtering
journal, January 2009
- Münch, Beat; Trtik, Pavel; Marone, Federica
- Optics Express, Vol. 17, Issue 10
Saturated Reconstruction of a Volume of Neocortex
journal, July 2015
- Kasthuri, Narayanan; Hayworth, Kenneth Jeffrey; Berger, Daniel Raimund
- Cell, Vol. 162, Issue 3
Rigid Embedding of Fixed and Stained, Whole, Millimeter-Scale Specimens for Section-free 3D Histology by Micro-Computed Tomography
journal, January 2018
- Lin, Alex Y.; Ding, Yifu; Vanselow, Daniel J.
- Journal of Visualized Experiments, Issue 140
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad
Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography
journal, September 2017
- Dyer, Eva L.; Gray Roncal, William; Prasad, Judy A.
- eneuro, Vol. 4, Issue 5
Structural and molecular interrogation of intact biological systems
journal, April 2013
- Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon
- Nature, Vol. 497, Issue 7449, p. 332-337
In vivo small-animal imaging using micro-CT and digital subtraction angiography
journal, August 2008
- Badea, C. T.; Drangova, M.; Holdsworth, D. W.
- Physics in Medicine and Biology, Vol. 53, Issue 19
The Human Cell Atlas.
text, January 2017
- Regev, Aviv; Teichmann, Sarah; Lander, Eric S.
- Apollo - University of Cambridge Repository
Imaging applications of synchrotron X-ray phase-contrast microtomography in biological morphology and biomaterials science. I. General aspects of the technique and its advantages in the analysis of millimetre-sized arthropod structure
journal, July 2007
- Betz, Oliver; Wegst, Ulrike; Weide, Daniela
- Journal of Microscopy, Vol. 227, Issue 1
Basics of cytology
journal, January 2011
- Al-Abbadi, MousaA
- Avicenna Journal of Medicine, Vol. 1, Issue 1
Comparative analysis of fixation and embedding techniques for optimized histological preparation of zebrafish
journal, June 2018
- Copper, Jean E.; Budgeon, Lynn R.; Foutz, Christina A.
- Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, Vol. 208
Acquisition, optimization and interpretation of X-ray computed tomographic imagery: applications to the geosciences
journal, May 2001
- Ketcham, Richard A.; Carlson, William D.
- Computers & Geosciences, Vol. 27, Issue 4
Quantifying mesoscale neuroanatomy using X-ray microtomography
preprint, January 2016
- Dyer, Eva L.; Roncal, William Gray; Fernandes, Hugo L.
- arXiv
Synchrotron X-ray tomographic microscopy of fossil embryos
journal, August 2006
- Donoghue, Philip C. J.; Bengtson, Stefan; Dong, Xi-ping
- Nature, Vol. 442, Issue 7103
Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis
journal, April 2014
- Susaki, Etsuo A.; Tainaka, Kazuki; Perrin, Dimitri
- Cell, Vol. 157, Issue 3
Observations on Histological Methods Involving the use of Phosphotungstic and Phosphomolybdic Acids, with Particular Reference to Staining with Phosphotungstic Acid/Haematoxylin
journal, September 1962
- Bulmer, D.
- Journal of Cell Science, Vol. s3-103, Issue 63
Works referencing / citing this record:
Micro-computed tomography as a platform for exploring Drosophila development
journal, November 2019
- Schoborg, Todd A.; Smith, Samantha L.; Smith, Lauren N.
- Development, Vol. 146, Issue 23
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad Digital Repository
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad Digital Repository
Zebrafish: An Emerging Model for Orthopedic Research
journal, December 2019
- Busse, Björn; Galloway, Jenna L.; Gray, Ryan S.
- Journal of Orthopaedic Research, Vol. 38, Issue 5
Taking a closer look at whole organisms
journal, June 2019
- Ichino, Noriko; Ekker, Stephen C.
- eLife, Vol. 8
Data from: Computational 3D histological phenotyping of whole zebrafish by X-ray histotomography
dataset, January 2019
- Ding, Yifu; Vanselow, Daniel J.; Yakovlev, Maksim A.
- Dryad