Quantitative Analysis of Crouzon Mouse Calvarial Morphology by Synchrotron Tomography

Authors: Alessandro Borghi (Imperial College London) , Alessandra Carriero (Imperial College London) , Naiara Rodriguez-florez (University College London) , Michael Doube (Royal Veterinary College) , Andrew Bodey (Diamond Light Source) , Silvia Schievano (University College London) , Erwin Pauws (University College London) , David Dunaway (Great Ormond Street Hospital) , Owase Jeelani (Great Ormond Street Hospital)
Co-authored by industrial partner: No

Type: Conference Paper
Conference: 43rd Annual Meeting of International Society for Pediatric Neurosurgery
Peer Reviewed: No

State: Published (Approved)
Published: October 2015
Diamond Proposal Number(s): 9860

Open Access Open Access

Abstract: Heterozygous Fgfr2C342Y mice show premature fusion of craniofacial sutures which causes mid-face shortening and coronal craniosynostosis. We investigated the skull bone morphology of two weeks old mutant mice and compared with age-matched wild type using high resolution synchrotron CT (sCT). Calvaria from 2 week old wild type (WT, n = 5) and mutant (C342Y, n = 5) mice were collected and skin and soft tissue removed. C342Y calvaria showed clear phenotypic features such as coronal synostosis and brachycephaly. sCT was performed at Diamond Light Source (Oxford, UK). Cross sections were processed in MIMICS (MATERIALISE) for 3D reconstruction. Image processing was performed on a 1mm x 1mm region of interest (ROI) from the frontal bone: porosity was extracted using morphological operations. Bone volume (BV), bone surface (BS) and TV (volume of the ROI) were measured. The mutant calvaria showed features typical of Crouzon syndrome: a visual inspection showed a higher curvature and undulation in the sagittal as well as interfrontal suture of the mutant mice. The mutant population showed a lower bone volume fraction (BV/TV 54.79%±13.59% vs 87.34%±4.45%, p<0.01) and a higher specific bone surface (BS/TV 12.01±1.20% vs 7.54±0.93%, p<0.01). This was most pronounced in the frontal bone, where abnormalities in the vasculature were also observed (as compared to WT frontal bone and mutant parietal bone). Skulls of Fgfr2C342Y mice show skull defects, similarly to children affected by Crouzon syndrome: a novel observation is that the bone architecture of the frontal bone is affected specifically in the C342Y mutant. This may reflect the different embryonic origin of the frontal and parietal bones. The quantitative analysis of the microscopic morphology constitutes an important tool for understanding the skull development, which will provide critical information for surgical planning.

Subject Areas: Biology and Bio-materials

Beamlines: I13-2-Diamond Manchester Imaging