High-Resolution Magnetic Resonance Histology of the Embryonic and Neonatal Mouse: A 4D Atlas and Morphologic Database

Alexandra Petiet, Matthew H. Kaufman, Matthew M. Goddeeris, Jeffrey L. Brandenburg, Susan A. Elmore, G. Allan Johnson

Proceedings of the National Academy of Sciences U S A 105(34):12331-12336, 2008. PMCID: PMC2527911

Engineered mice play an ever-increasing role in defining connections between genotype and phenotypic expression. The potential of magnetic resonance microscopy (MRM) for morphologic phenotyping in the mouse has previously been demonstrated; however, applications have been limited by long scan times, availability of the technology, and a foundation of normative data. This article describes an integrated environment for high-resolution study of normal, transgenic, and mutant mouse models at embryonic and neonatal stages. Three-dimensional images are shown at an isotropic resolution of 19.5 microns (voxel volumes of 8 pL), acquired in 3 h at embryonic days 10.5-19.5 (10 stages) and postnatal days 0-32 (6 stages). A web-accessible atlas encompassing this data was developed, and for critical stages of embryonic development (prenatal days 14.5-18.5), more than 200 anatomical structures have been identified and labeled. Also, matching optical histology and analysis tools are provided to compare multiple specimens at multiple developmental stages. The utility of the approach is demonstrated in characterizing cardiac septal defects in conditional mutant embryos lacking the Smoothened receptor gene.

Finally, a collaborative paradigm is presented that allows sharing of data across the scientific community. This work makes magnetic resonance microscopy of the mouse embryo and neonate broadly available with carefully annotated normative data and an extensive environment for collaborations.

 

CIVM makes many types of data acquired for published and yet unpublished studies available through our CIVM VoxPort application. Use of VoxPort is free. Registration is required. Register for VoxPort access now. A new browser window or tab will open.

We ask that you provide contact information, and agree to give credit to the Duke Center for In Vivo Microscopy for any written or oral presentation using data from this site. Please use the following acknowledgement: Imaging data provided by the Duke Center for In Vivo Microscopy NIH/NIBIB (P41 EB015897).

Instructions: Click on a link below. A new browser window or tab will open where you will be prompted to login to CIVMVoxPort. If you do not have login credentials, follow the instructions to register for access. After you login, come back to this page and re-click on a link below to go directly to the desired page.

This online database is a collection of 3-dimensional MR datasets: This online database is a collection of 3-dimensional MR datasets:

• Normal C57BL/6 mouse embryos from embryonic day E10.5 to E19.5
• Normal C57BL/6 mouse neonates from post-natal day 0 to 32
• Mutant mouse embryos with cardiac septation defects (conditional ablation of the Smoothened receptor gene, Mef2C-AHF-Cre;Smo^flox/- mutants)

The database also features:

• Color-labeled hearts of normal and abnormal mouse embryos
• Labeled whole bodies of C57BL/6 mouse embryos, viewable in MBAT
• H&E sections of C57BL/6 mouse embryos matching MR images

 

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The link from the button below will access CIVMVoxPort, where you can select any thumbnail to browse slices from the corresponding dataset. To view structure labels, select "Open in VoxStation" from the pull-down menu at the upper right corner of the CIVMVoxPort page, then the "Go" button to launch VoxStation, a Java Web Start application that lets you view datasets in three planes.

Below is a screen shot for an example of a volume dataset (C57BL/6 normal fetus at E15.5) that can be found in CIVMVoxPort:
 

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Related References

• Petiet A, Hedlund LW, Johnson GA, Staining methods for magnetic resonance microscopy of the rat fetus, Journal of Magnetic Resonance Imaging, 25: 1192-1198 (2007). PMCID: PMC2747382
• Goddeeris MM, Schwartz R, Klingensmith J, Meyers EN, Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development, Development, 134: 1593-1604 (2007). PMC:PMCID: 2746050
• Verzi MP, McCulley DJ, De Val S, Dodou E, Black BL, The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field, Developmental Biology, 287: 134-145 (2005). Open Access
• Zhang XM, Ramalho-Santos M, McMahon AP, Smoothened mutants revealed redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node, Cell, 106: 781-792 (2001). Open access through Science Direct

 

Acknowledgements

All MR imaging was performed at the Duke Center for In Vivo Microscopy, under NIH/NCRR grant P41 RR005959 and NCI SAIRP grant U24 CA092656. This work was also supported by the Mouse Bioinformatics Research Network (MBIRN) NIH/NCRR grant U24 RR021760.