Estimation of independent non-linear deformation modes for analysis of craniofacial malformations in crouzon mice

Crouzon syndrome is a genetic disease resulting in premature fusion of cranial sutures and synchondroses causing craniosynostosis. A decade ago the Crouzon gene was discovered, and recently the first mouse model of the syndrome was generated. In this study, a set of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. We present for what we believe is the first time, a statistical deformation model based on independent component analysis (ICA). A set of deformation parameters for each mouse was calculated using a B-spline-based non-rigid registration. From the parameters controlling the deformations for each subject, the statistical model was estimated. ICA is demonstrated to provide localized deformation components, many of which give a clear separation between Crouzon and wild-type mice. This is a clear improvement of a previous principal component-based model, which only provided one global deformation component describing the disease. The ICA components allow interpretation of each deformation feature to be carried out independently of other features, and provides a basis for linking the observed craniofacial malformations to the fusing of sutures. ICA revealed an interesting new finding, not previously reported in the literature, namely asymmetries in the head in Crouzon mice. This phenomenon is probably caused by asymmetric closure of craniofacial sutures.