Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2

Hildur Ólafsdóttir, Tron Andre Darvann, Nuno V. Hermann, Estanislao Oubel, Bjarne Kjær Ersbøll, Alejandro F. Frangi, Per Larsen, Chad A. Perlyn, Gillian M. Morriss-Kay, Sven Kreiborg

    Research output: Contribution to journalJournal articleResearchpeer-review


    Crouzon syndrome is characterised by premature fusion of sutures and synchondroses. Recently the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of Micro CT scannings of the skulls of wild-type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild-type mouse Micro CT volumes using (i) affine and (ii) nonrigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landmarks from two different observers and automatically assessed landmarks. Both of the automatic approaches were within the inter-observer accuracy for normal specimens, and the nonrigid approach was within the inter-observer accuracy for the Crouzon specimens. Four linear measurements, skull length, height and width and inter-orbital distance, were carried out automatically using the two different approaches. Both automatic approaches assessed the skull length, width and height accurately for both groups of mice. The nonrigid approach measured the inter-orbital distance accurately for both groups while the affine approach failed to assess this parameter for both groups. Using the full capability of the nonrigid approach, local displacements obtained when registering the nonrigid wild-type atlas to a nonrigid Crouzon mouse atlas were determined on the surface of the wild-type atlas. This revealed a 0.6 mm bending in the nasal region and a 0.8 mm shortening of the zygoma, which are similar to characteristics previously reported in humans. The most striking finding of this analysis was an angulation of approximately 0.6 mm of the cranial base, which has not been reported in humans. Comparing the two different methodologies, it is concluded that the nonrigid approach is the best way to automatically assess linear skull parameters. Furthermore, the nonrigid approach is essential when it comes to analysing local, nonlinear shape differences.
    Original languageEnglish
    JournalJournal of Anatomy
    Issue number1
    Pages (from-to)37-52
    Publication statusPublished - 2007


    • mouse model
    • Crouzon syndrome
    • shape deviations
    • affine image registration
    • local displacements
    • computational atlas
    • Nonrigid image registration
    • craniofacial mouse atlas


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