Predicting calvarial growth in normal and craniosynostotic mice using a computational approach

Abstract

During postnatal calvarial growth the brain grows gradually and the overlying bones and sutures accommodate that growth until the later juvenile stages. The whole process is coordinated through a complex series of biological, chemical and perhaps mechanical signals between various elements of the craniofacial system. The aim of this study was to investigate to what extent a computational model can accurately predict the calvarial growth in wild-type (WT) and mutant type (MT) Fgfr2 mice displaying bicoronal suture fusion. A series of morphological studies were carried out to quantify the calvarial growth at P3, P10 and P20 in both mouse types. MicroCT images of a P3 specimen were used to develop a finite element model of skull growth to predict the calvarial shape of WT and MT mice at P10. Sensitivity tests were performed and the results compared with ex vivo P10 data. Although the models were sensitive to the choice of input parameters, they predicted the overall skull growth in the WT and MT mice. The models also captured the difference between the ex vivoWT and MT mice. This modelling approach has the potential to be translated to human skull growth and to enhance our understanding of the different reconstruction methods used to manage clinically the different forms of craniosynostosis, and in the long term possibly reduce the number of re-operations in children displaying this condition and thereby enhance their quality of life.

Predicting calvarial morphology in sagittal craniosynostosis

“…This was similar to our previous study on modelling the natural calvarial growth from 0-12 months of age 17 . The model was loaded via thermal expansion of the ICV, as previously described 17,19 . A linear isotropic expansion was applied to the ICV, where the pre-operative ICV (measured at 648 ml) was expanded to the follow up ICV (measured at 1320 ml) in seven intervals.…”

“…The patterns of contact pressure on the intracranial volumes were also compared as an indication of how each of the considered cases affected the brain growth. Note (1) the changes in the calvarial morphology at each interval is not included here but such results are presented for our previous work on predicting calvarial morphology in mouse and normal human skull growth 17,19,20 . (2) all methods were carried out in accordance with relevant guidelines and regulations.…”

“…Finite element (FE) method is a powerful numerical technique used to analyse a wide variety of engineering problems 15 FE method has the potential to predict the morphological changes during the skull growth [16][17][18][19][20] and to compare the biomechanics of different reconstruction techniques. This can advance our understanding of the optimum management, not only of sagittal synostosis but all forms of craniosynostosis [21][22][23] .…”

An Overview of Modelling Craniosynostosis Using the Finite Element Method

“…In this respect, intracranial volume or brain soft tissue can be modelled and expanded based on the changes in the intracranial volume to take into account the loading arising from the growing brain [Jin et al, 2014;Libby et al, 2017;Marghoub et al, 2018]; (2) modelling the sutures -it is well established that the sutures can release the local mechanical strain [e.g., Moss,80 1954; Jaslow and Biewner, 1995;Moazen et al, 2013]. It is important to include the sutures to develop more realistic models of the craniofacial system [Jin et al, 2013;Libby et al, 2017;Weickenmeier et al, 2017;Marghoub et al, 2018]. Sutures can be segmented during the reconstruction of the model of the skull via image processing and incorporated into the FE simulation; (3) modelling dura mater and other soft tissues -including other soft tissues such as dura mater and muscles will evidently lead to more realistic FE models of the skull growth.…”

“…At the same time in the past 20 years, evolutionary biologists and functional morphologists have widely used this technique to understand the form and function of craniofacial systems in an evolutionary context [e.g., Rayfield, 2007;Moazen et al, 2009;Wang et al, 2010;O'Higgins et al, 2011;Prado et al, 2016]. More recently, this technique has been used to understand the biomechanics of craniofacial development and its associated congenital diseases such as cleft lip/palate and craniosynostosis [e.g., Remmler et al, 1998;Pan et al, 2007;Khonsari et al, 2013;Jin et al, 2014;Lee et al, 2017;Marghoub et al, 2018].…”