Heart Segmentation for the Amsterdam Mouse Heart Atlas Project

 

Background

Members of the departments of Anatomy & Embryology (A&E) and Medical Informatics (KIK) of the AMC cooperate in the development of an application for automatically fitting 2D sections of an embryonic mouse heart into 3D computer reconstructions of mouse hearts. A prototype of this application, written in Matlab, is already finished. The application is being developed with two main goals in mind. The first goal is to give users the opportunity to get information about the orientation of their tissue sections. The second goal is to collect and make available gene expression information within its anatomic context.

In research in cardiac development it is unavoidable to use serially sectioned biological material for 3D computer reconstructions, for reasons like the required level of detail or the limited penetration of staining agents into whole mount staining procedures (Ruijter et al. 2004). Soufan et al. (2003, 2007) reconstructed a series of developing mouse hearts from sections of hearts in which in situ hybridization with markers for myocardium was used to allow for the automatic selection of the myocardium. The 3D reconstructions show details and provide insights that are not clear from studying the series of sections themselves. Thus, the reconstructions are a useful tool to increase our understanding of the development of the myocardium, which is important because of the high incidence and seriousness of congenital heart diseases.

Although 3D reconstructions can provide additional insights, not all researchers decide to stain the required complete series of sections. In many cases, only a limited number of sections are stained for specific proteins or mRNAs. In fact, in some recent research projects high-throughput methods are employed to generate vast amounts of such individual sections: Carson et al. (2002), Raymond et al. (2002), Visel et al. (2004). Moreover, these sections are not always of known orientation and possibly not exactly timed. Interpretation of such sections is then hampered by lack of information on the anatomical and developmental context.

The automatic fitting of such individual sections into a reference series of 3D reconstructions can be used as a tool for data collecting for a reference atlas. Being able to display gene expression in its 3D context would constitute a huge improvement over (typical) gene expression databases where the location of the gene expression is only described in general terms.

 

Project description

The present version of the automatic fitting program works on images of sections which are stained with markers for myocardium, which enables the automatic selection of the myocardium using a relatively simple thresholding procedure. The main goal of the proposed project is to make it possible to select the heart in an image of a section which is not specifically stained for heart tissue. The goal of the Amsterdam Mouse Heart Atlas Project is to automatically fit arbitrary 2D sections into the 3D reconstructions. It is therefore necessary that the fitting algorithm can also be applied to sections where the myocardium is not, or only partially, labeled.

After a literature study, a few promising segmentation methods should be selected and tested (using available implementations) for their suitability for the task of segmenting the heart on images of typical sections without the myocardium markers. The best suited method should then be refined for actual implementation in the prototype of the fitting application.

 

 

Suggestions for further reading:

See Ruijter et al. (2004) for information on techniques for three-dimensional visualization of gene expression patterns and Christiansen et al. (2006) for a description of an existing gene expression database developed with similar intentions as those underlying the Amsterdam Mouse Heart Atlas. See http://en.wikipedia.org/wiki/Segmentation_(image_processing) for a brief overview of segmentation methods.

 

References

Carson et al. (2002) J. Carson, C. Thaller and G. Eichele, A transcriptome atlas of the mouse brain at cellular resolution, Current Opinion in Neurobiology 12 (2002) 562-565.

Christiansen (2006) Jeffrey H. Christiansen, Yiya Yang, Shanmugasundaram Venkataraman, Lorna Richardson, Peter Stevenson, Nicholas Burton, Richard A. Baldock and Duncan R. Davidson; EMAGE: a spatial database of gene expression patterns during mouse embryo development, Nucleic Acids Research, 2006, Vol. 34, Database issue D637–D641

Raymond et al. (1989) A. Raymond, V. Marigo, M. Yaylaoglu, A. Leoni, C. Ucla, N. Scamuffa, C. Cacciopoll, E. Dermitzakis, R. Lyle, S. Banfi, G. Eichele, S. Antonarakis, and A. Ballabio, Human chromosome 21 gene expression atlas in the moude, Nature 420 (2002) 582-586.

Ruijter et al. (2004) Jan M. Ruijter, Alexandre T. Soufan, Jaco Hagoort, and Antoon F.M. Moorman, Molecular imaging of the embryonic heart: Fables and facts on 3D imaging of gene expression patterns, Birth Defects Research (Part C) 72:224–240 (2004)

Soufan et al. (2003) A.T. Soufan, J. Ruijter, M. van den Hoff, P. de Boer, J. Hagoort, A. Moorman, 3D reconstruction of gene expression patterns during cardiac development, Physiological Genomics 13 (2003) 187-195.

Soufan et al. (2007) A.T. Soufan, G. van den Berg, P. D. Moerland, M. M. G. Massink, M. J. B. van den Hoff, A. F. M. Moorman, J. M. Ruijter, Three-dimensional measurement and visualization of morphogenesis applied to cardiac embryology, Journal of Microscopy, Vol. 225, 2007 March 3, pp. 269–274

Visel et al. (2004) Visel A, Thaller C, Eichele G,  GenePaint.org: an atlas of gene expression patterns in the mouse embryo. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D552-6. 

 

Contact:

Frans Voorbraak (Medical Informatics, f.p.voorbraak@amc.uva.nl)