@ARTICLE\{IMM2007-04934,
    author       = "H. \'{O}lafsd\'{o}ttir and T. A. Darvann and N. V. Hermann and E. Oubel and B. K. Ersb{\o}ll and A. F. Frangi and P. Larsen and C. A. Perlyn and G. M. Morriss-Kay and S. Kreiborg",
    title        = "Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation  Fgfr2\^C342Y",
    year         = "2007",
    month        = "jul",
    keywords     = "Nonrigid image registration, affine image registration, computational atlas, craniofacial mouse atlas, local displacements, shape deviations, Crouzon syndrome, mouse model",
    pages        = "37-52",
    journal      = "Journal of Anatomy",
    volume       = "211",
    editor       = "",
    number       = "1",
    publisher    = "Blackwell Publishing",
    url          = "http://www2.compute.dtu.dk/pubdb/pubs/4934-full.html",
    abstract     = "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."
}