@article{ce3850bfeff4407ea8a7b816854756b1,
title = "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.",
author = "Yifu Ding and Vanselow, {Daniel J.} and Yakovlev, {Maksim A.} and Katz, {Spencer R.} and Lin, {Alex Y.} and Clark, {Darin P.} and Phillip Vargas and Xuying Xin and Copper, {Jean E.} and Canfield, {Victor A.} and Ang, {Khai C.} and Yuxin Wang and Xianghui Xiao and Carlo, {Francesco De} and Rossum, {Damian B.Van} and Riviere, {Patrick La} and Cheng, {Keith C.}",
note = "Funding Information: The authors are grateful for the unusually extensive and sustained collaborative effort required across disciplines and institutions, including that of technical and administrative support staff. We thank Steven Peckins and Drs. Timothy Cooper and Gordon Kindlemann for critical insight in the early stages of the project{\textquoteright}s conception and development. This paper is dedicated to the memory of Dr. Betty PT Cheng. The investigators acknowledge NIH funding support (PI: KCC, R24-RR017441, and PI: KCC, R24-OD018559), pilot award funding to KCC from the Huck Institutes of the Life Sciences and the Institute for Cyber Science, PSU, and support from the Pennsylvania Tobacco Fund and Penn State Department of Pathology for the Penn State Functional Genomics Core. The use of the APS, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the US DOE under contract no. DE-AC02-06CH11357. The authors, and not the funding agencies, are solely responsible for the content of this work. Funding Information: The authors are grateful for the unusually extensive and sustained collaborative effort required across disciplines and institutions, including that of technical and administrative support staff. We thank Steven Peckins and Drs. Timothy Cooper and Gordon Kindlemann for critical insight in the early stages of the project?s conception and development. This paper is dedicated to the memory of Dr. Betty PT Cheng. The investigators acknowledge NIHNational Institutes of Health funding support (PI: KCC, R24-RR017441, and NIHNational Institutes of HealthPI: KCC, R24-OD018559), pilot award funding to KCC from the Huck Institutes of the Life Scien- ces and the Institute for Cyber Science, PSU, and support from the Pennsylvania Tobacco Fund and Penn State Department of Pathology for the Penn State Functional Genomics Core. The use of the APS, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the US DOE under contract no. DE-AC02-06CH11357. The authors, and not the funding agencies, are solely responsible for the content of this work. Publisher Copyright: {\textcopyright} Ding et al.",
year = "2019",
month = may,
doi = "10.7554/eLife.44898",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}