example images and movies
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In this page are a number of images and movies generated as part of the Mouse Atlas Gene Expression Database Project.  The project is a collaboration between the MRC Human Genetics Unit and the University of Edinburgh Department of Anatomy. The Human Genetics Unit is the co-ordinating site  - principal investigators, R.A. Baldock (computing) and D.R. Davidson (biology).  The principal investigators at the Department of Anatomy are M.H. Kaufman and J.B.L. Bard.  See the People page for all the members of the project.

The images shown below illustrate the reconstruction process and a number of preliminary results. Most of these images have appeared as illustrations in journal papers or as parts of posters or conference presentations.  In all of the images below, click on the image to get a larger version or the corresponding movie sequence.

The images have been divided into the categories:

  • Processing:- sample images from the processing steps to generate the atlas.
  • 3-D Voxel Reconstructions:- images of the voxel models.
  • Anatomy:- images of the defined anatomy using different visualisation methods
  • Database Interfaces:- picture of some of the prototype image database interfaces.
  • Gene Expression:- picture of some gene expression domains mapped onto the 9-day embryo.
  • Movies:- some movie sequences.

 
This page is under construction and the numbers of images and movies will be extended to cover the range of embryos now completed within the atlas (most of TS1-TS14).


Processing

The software show in the images below has been developed as part of the Mouse Atlas project. The image processing is based on the "woolz" system developed at the MRC by many authors. This will become a public domain system in 1998. The user interfaces are implemented in C and C++ and use Motif for the graphical interface. More details are available from the primary author for the programs listed in the caption. More details of the reconstruction process are also available.

Image capture using "xmgrab" - software developed at the MRC for digital image capture using the MRC S-Bus and digital camera interface with the Xillix Technologies Xillix 1400 camera. This picture shows the use of overlays for rough registration of sections. 

Author: Richard Baldock.

Digitisation of sections of an E17 embryo using the facilities for "patching" within xmgrab - i.e. the building of a single image from a mosaic of tiles.
Reconstruction of a 3D voxel image from a series of 2D sections. The program reconstruct allows manual and automatic registration of sections as well as grey-level normalisation and in future will provide mechanisms for warping images. This view shows the interface for section editing and review. 

Author: Bill Hill.

A second view of the reconstruct program showing the manual tie-point interface.
After registration of the sections, random distortions in each section are removed using the warping program which allows arbitrary local deformations of the images to match the biological structures. 
This image shows the effect of warping on the cross-section through a 7.5 day mouse embryo. The reconstruction of individual cell nuclei and thin membranes is clear even through the occasional section with severe grey-level artefacts. 

Author: Elizabeth Guest - contact Richard Baldock.

The early embryos in the atlas are segemented into their constituent anatomical components using a manual "painting" program. The program paint allows the delineation of arbitrary 3D structures by successively defining the volume occupied by that structure in 2D sections. The program allows simultaneous views at any viewing orientation, and the structure or domain can be painted within any view. Paint also provides 3D feedback of the structures defined as well as a number of image-processing tools for "power-assistance". These include simple fill and thresholding as well a automatic tracking through the stack. This image shows the painting on a 8.5-day mouse embryo. 

Author: Richard Baldock.

Paint can also be used to conveniently review domains defined by an automatic or semi-automatic process (e.g. segmentaion of the whole 3D image). The review domain is read in and the user is prompted to designate the labelled region of the domain to the appropriate anatomical component.

 


3-D Voxel Reconstructions

At each stage of development grey-level voxel reconstructions of the embryo are made from images of serial histological sections. For embryos older than 8 days of development (Theiler Stage12; Theiler, K. (1989) The House Mouse, Atlas of development. Springer-Verlag, New York) the sections are cut from wax-embedded embryos at a nominal section thickness of 7 um. The younger embryos are cut from plastic with section thickness of 2 um. The original digitsations are at roughly 3 times the final resolution so that the image processing steps of registration and warping do not degrade the information content of the image.  All the reconstructions below were made using the MRC woolz software. The wax histological sections are from Professor M Kaufman, Department of Anatomy and the serial plastic sections cut by Allyson Ross at the Human Genetics Unit.
 
Block view of part of the digitised 9-day embryo model (based on 307, 7um wax sections)displayed using SunVision (Sun Microsystems).  The view illustrates sections made digitally through the surface of the block containing the embryo model.
A similar block view of the digitised 8.5-day embryo model (based on 243 7um wax sections)displayed using SunVision (Sun Microsystems).
A block view of the 7.5 day embryo model showing arbitrary digital sections through the voxel model. This reconstruction is based on plastic sections and has voxel size 2x2x2um.
 
 


Anatomy

The anatomical structures of the nomenclature database are defined within the corresponding voxel model by a process of image segmentation. In the earlier embryos this is primarily a manual process of painting the voxel images to define the anatomical domains.  All the anatomy displayed below has been defined, using the paint program, by Renske Brune at the Department of Anatomy, University of Edinburgh. The images are displayed using paint and using AVS 5 (contact Margaret Stark, MRC HGU, for more information of our use of AVS5 and AVS Viz).
 
 
Selected anatomical domains of the 9-day embryo model displayed in section mode with overlaid anatomical components. Colours are re-used for different painted domains, these images show the resolution of the Mouse Atlas painted domains. 
 
 
This pseudo-3D view of the TS14 (E9.0) embryo model displays the painted domains of the neural tube (yellow), gut (red), heart (light blue), somites (green), optic vesicles (dark blue), otic pit (lime green) and primitive streak (mauve). These tissues of the embryo are enclosed in translucent surface ectoderm. 
 
This pseudo-3D view of the TS13 (E8.5) embryo model displays the painted domains of the neural tube (yellow), gut (red), heart (light blue), somites (green), optic vesicles (dark blue), otic placode (lime green) and streak (mauve). These tissues of the embryo are enclosed in translucent surface ectoderm. 
 
  Stereo pair of images showing selected vessels of the 9-day embryo model.  The stereo view can be seen by crossing your eyes and merging the two images, either with this view or the enlarged version. The angular separation between the two views is 12 degrees.
 
 


Database Interfaces


The Object Oriented Database and the interfaces have been developed by Christophe Dubreuil at the MRC Human Genetics Unit. The pictures below are of a number of prototype interfaces providing access to the anatomical nomenclature as well as the reconstructions and anatomical domains. The section viewers are the first example of a WWW interface giving access to arbitrary sections views of embryo images held in a central database. The user is able to highlight specific tissues or simply move the mouse over the image to display the corresponding tissue name.
 
The standard nomenclature database has been implemented as an Object-Oriented database using ObjectStore. The components for each Theiler stage are organised as a hierarchy and can be displayed as a tree of components. This interface allows the user to browse the tree, expanding/collapsing it as required. This is an early prototype without and additional facilities for display of other data (e.g. lineage, groups, annotations etc.). The Theiler Info button links to further information on the specific stage. 

Author: Christophe Dubreuil 

The database can be searched for any specific named component. The results are returned as a simple time-ordered list. 

Author: Christophe Dubreuil 

Identifying tissues in sections 
The database will be delivered via a CORBA interface and the interfaces for submission, query, and analysis of gene expression data will be implemented in java. This prototype interface accesses a database of grey-level reconstructions and the defined anatomy. Arbitrary section views of the reconstruction can be selected and will be returned as well as the anatomy components present. As the cursor is passed over the section view the corresponding anatomy is displayed. Individual components can be selected and highlighted or the fully "painted" image displayed. 

Author: Christophe Dubreuil 

An alternative section viewer has also been implemented that provides a 3D navigational block that shows the current section plane to indicate the context of the histological section being viewed. This interface allows the user to interactively set the fixed points used for navigation. If two fixed points are set (a fixed line) then the section viewing controls become a single control slider for the rotation about that line. Elements of this interface will be integrated with the anatomy database tree and domain viewer. 

Author: Oystein Sorensen and  Christophe Dubreuil 


 
 


Gene Expression

The database currently encodes domains of gene-expression in the same way that anatomical domains are mapped onto the reference voxel model. Gene expression domains can be defined using MAPaint in the same way but, whereas tissues are defined to be non-overlapping, no such restriction applies to gene-expression. In future versions of the database the gene-expression data will be extended to include grey-value (strength) information.

WT1 expression (red) on a section of the E9 (Theiler Stage 14) embryo from the Edinburgh Mouse Atlas. The gut epithelium is shown in yellow and the neural tube in a blue overlay. WT1 is expressed in the presumptive mesothelium of the coelom and in the intermediate mesoderm (ventral to the somites).
Reference: Armstrong et al, ....

Mapped gene-expression data in the 9.5 dpc (Theiler stage 15) mouse embryo. The expression pattern of MSX1 is shown in green, MSX2 in red and the region showing co-expression of the genes is displayed in orange.

The gene-expression data has been mapped from an experimental embryo onto the standard atlas reconstruction using sofware developed at the MRC HGU to warp the signal image onto an arbitrary section through the standard Atlas model. For more information of the mapping process used to produce this image see /Documentation/Technical/ge_mapping.html


Movies

All the movies below are in MPEG format for which viewers can be obtained for all machine architectures (see for example http://www.mpeg.org/index.html/). Some of the movie files below are quite large so be prepared to wait for the data to download. These sequences show best on a 24-bit display and when viewed on an 8-bit (256 colours) display may appear degraded. If you have problems viewing these files please seek help from your local computing administrator/services.
 
 
This movie shows an animation of all the grey-level sections from which the 3-D reconstruction  of the 9-day (TS14) embryo model was made.  (size 940 KBytes).
Rotating view of selected 9-day anatomy with a grey-level section (size 640 KBytes). A combined version of this and the previous movie is available in small mpg, small avi (2.0MBytes) or large mpeg (5.2 Mbytes) versions.
Rotating view of the 9-day cardiovascular system. Each turn remove a selection of the tissues (3.3 MBytes).
Rotating view of selected tissues of the 9-day reconstruction. Each turn remove a few tissues (1.9 MBytes).
"Striptease" view of some tissues of the 9-day reconstruction. Each step removes a few tissues (1.6 MBytes).
Rotating 9-day embryo model displayed using vtk either  in colour (287KBytes) or grey (244KBytes). This reconstruction was made by direct volume rendering which generates an image similar to that seen when an embryo is illuminated with transmitted light.
Reconstruction of the 11-day eye model showing the painted optic cup, optic stalk and developing lens. This reconstruction has not been corrected for systematic distortion . Movie size 585 KBytes. 

This reconstruction was made by students from Craigmount High School, Edinburgh, as part of a Nuffield Science Foundation summer project.


Web page contact: genexweb@hgu.mrc.ac.uk Last modified:
6/11/2002
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