A Practical Workflow for Making Anatomical Atlases for Biological Research

Biomedical Applications A Practical Workflow for Making Anatomical Atlases for Biological Research Yong Wan, A. Kelsey Lewis, Mary Colasanto, Mark van Langeveld, Gabrielle Kardon, and Charles Hansen ■ University of Utah n anatomical atlas provides a detailed map However, biology researchers still ask, “Is there a for medical and biological studies of anat- set of tools we can use or a practical workflow we omy. These atlases are important for un- can follow so that we can easily build models from Aderstanding normal anatomy and the development our biological data?” To help answer this question, and function of structures, and for determining computer scientists have developed many algo- the etiology of congenital abnormalities. Unfor- rithms, tools, and program codes. Unfortunately, tunately, for biologists, generating such atlases most of these researchers have tackled only one is difficult, especially ones with aspect of the problem or provided solutions to spe- the informative content and aes- cial cases. So, the general question of how to build The anatomical atlas has thetic quality that characterize anatomical atlases remains unanswered. been at the intersection human anatomy atlases. Build- For a satisfactory answer, biologists need a prac- of science and art for ing such atlases requires knowl- tical workflow they can easily adapt for different centuries. With certain edge of the species being studied applications. In addition, reliable tools that can adaptations, the computer and experience with an art form fit into the workflow must be readily available. -Fi graphics artist’s workflow that can faithfully record and nally, examples using the workflow and tools to and tools are practical for present this knowledge, both of build anatomical atlases would demonstrate these building high-quality atlases, which require extensive training resources’ utility for biological research. essential to biological and in considerably different fields. To build a mouse limb atlas for studying the medical research. Using this (For some background on ana- development of the limb musculoskeletal system, tomical atlases, see the related University of Utah biologists, artists, and computer workflow, researchers built sidebar.) scientists have designed a generalized workflow an atlas of the mouse limb With the latest innovations for generating anatomical atlases. We adapted it musculoskeletal system. in data acquisition and comput- from a CG artist’s workflow of building 3D mod- ing techniques, atlas building els for animated films and video games. The tools has changed dramatically. We can now create at- we used to build the atlas were mostly commer- lases from 3D images of biological specimens, al- cial, industry-standard software packages. Having lowing for high-quality, faithful representations. been developed, tested, and employed for indus- Labeling of structures using fluorescently tagged trial use for decades, CG artists’ workflow and antibodies, confocal 3D scanning of these labeled tools, with certain adaptations, are the most suit- structures, volume rendering, segmentation, and able for making high-quality anatomical atlases, surface reconstruction techniques all promise so- especially under strict budgetary and time limits. lutions to the problem of building atlases. Biological researchers have been largely unaware 70 September/October 2012 Published by the IEEE Computer Society 0272-1716/12/$31.00 © 2012 IEEE A Brief Introduction to Anatomical Atlases ruly an arena where science meets art, anatomical at- are difficult to make, store, and maintain. They hardly ever Tlases evolved as technologies advanced in both fields: achieve the level of detail required by scientific research and painting, printing, photography, microscopy, tomogra- are rarely used in biological and medical research. phy, and computer graphics. Whenever a novel technology Computer graphics transformed anatomical atlases. emerges, our knowledge of anatomy is enriched with both Computer-generated atlases allow for a 3D, manipulable exciting scientific findings and the increasingly detailed visualization of anatomy. Several 3D atlases have been information presented in atlases. generated for human anatomy, including the Visible Body Historically, an anatomical atlas has been a book of (www.visiblebody.com), Cyber-Anatomy (www.cyber- illustrations and text that systematically explains a particular anatomy.com), and Zygote’s anatomical-model library species’ anatomy. Naturally, human anatomy has been the (www.zygote.com). Because 3D models are commonly most studied. Atlases of human anatomy date back to such built by referencing 2D illustrations of anatomy books, build- renowned anatomists as Vesalius, Leonardo da Vinci, William ing 3D atlases is expensive and requires specialized personnel Hunter, and Henry Gray. Their creations are esteemed not with experience in digital modeling and anatomy. only for their scientific value but also as masterpieces of art. For biologists to build 3D anatomical models, using 3D The most influential printed human anatomy atlases available scanned biological samples is the most practical approach. are Gray’s,1 Frank Netter’s,2 and Thieme’s.3 Owing to noise and limited resolution, anatomical atlases The production and appearance of printed atlases have that directly use volume renderings of scanned 3D volumet- changed with the development of technology. Henry ric data6 usually can’t achieve the clarity of polygon-based Vandyke Carter, the illustrator of Gray’s book, drafted atlases, composed of objects modeled by representing his illustrations in reverse on boxwood, which was then their surfaces with polygons. There are several published engraved for printing.4 Netter enjoyed the convenience polygon-based anatomical atlases for biological research brought by photography and modern printing. He chose (for example, by Tao Ju7 and April DeLaurier and her col- gouache, a painting technique that could better render leagues8). However, easy-to-follow workflows and examples the highlights and shadows to give his illustrations a more are unavailable for biologists to learn to make such atlases. 3D look. The illustrations of Thieme’s Atlas of Anatomy were mostly hand drawn with Adobe Photoshop by Markus Voll and Karl Wesker. Although they largely follow the styles References established by their predecessors, the use of digital media 1. H. Gray and H.V. Carter, Anatomy: Descriptive and Surgical, gives their illustrations finer details, smoother tonal grada- 1st ed., J.W. Parker, 1858. tions, and better transparency effects. All these contribute to 2. F.H. Netter, Atlas of Human Anatomy, 5th ed., Elsevier, 2011. the clear representation of particular anatomical features. 3. A.M. Gilroy, B.R. MacPherson, and L.M. Ross, Atlas of Anatomy, Printed atlases of other biological species are relatively 1st ed., Thieme Medical Publishers, 2009. scarce, and those in existence are usually decades old. 4. R. Richardson, The Making of Mr. Gray’s Anatomy, 1st ed., For example, Eunice Greene’s Anatomy of the Rat5 was Oxford Univ. Press, 2008. published in 1935 and is still considered the definitive text 5. E.C. Greene, Anatomy of the Rat, reprint, Hafner, 1968. for identifying rodent anatomical structures. In particular, 6. K.H. Höhne et al., “A Volume-Based Anatomical Atlas,” IEEE Greene’s atlas serves as the anatomy text for the labora- Computer Graphics & Applications, vol. 12, no. 4, 1992, pp. tory mouse, one of the most important model organisms 72–78. in biology and medicine. 7. T. Ju, “Building a 3D Atlas of the Mouse Brain,” PhD thesis, Anatomical atlases are crucial to understanding normal Dept. of Computer Science, Rice Univ., 2005. anatomy and identifying congenital abnormalities. For edu- 8. A. DeLaurier et al., “The Mouse Limb Anatomy Atlas: An cational purposes, physical models are also sometimes built Interactive 3D Tool for Studying Embryonic Limb Patterning,” and used. They provide a unique 3D model of anatomy but BMC Developmental Biology, vol. 8, 2008, article 83. of these resources. By describing our experiences the musculoskeletal system during development. in this project, we hope to show biologists how Understanding how the musculoskeletal system is to use these resources to make anatomically accu- assembled is a fundamental question in develop- rate, high-quality, and useful anatomical atlases. mental biology. In addition, congenital defects in limb and musculoskeletal development are relatively Data Acquisition common in humans; understanding these defects’ The biologists who worked on the mouse limb atlas etiology is of interest to the medical community. are researching the cellular and molecular mecha- Mice are the primary model organism used to nisms governing the patterning and assembly of study limb musculoskeletal development. Not only IEEE Computer Graphics and Applications 71 Biomedical Applications Confocal Laser Scanning Microscopy are mouse and human development similar, but o capture the finely detailed structures from a biological also many genetic tools (such as the ability to cre- Tsample, such as a mouse limb, researchers tag structures using ate knockout mice—mice with a gene inactivated) different fluorescently labeled antibodies that bind only to par- and molecular reagents are available with mice. ticular structures (for example, tendons, muscles, and nerves). A To facilitate studying mouse limb development, confocal microscope excites the fluorescent tags with lasers, and the biologists wanted to create

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