Prenatal growth map of the mouse knee joint by means of deformable registration technique.

Mario Giorgi,Niamh C Nowlan,Vivien Sotiriou,Simone Conigliaro,Cristina Bignardi,Enrico Dall’Ara,Niccolo’ Fanchini,María Angeles Pérez

doi:10.1371/journal.pone.0197947

Abstract

Joint morphogenesis is the process during which distinct and functional joint shapes emerge during pre- and post-natal joint development. In this study, a repeatable semi-automatic protocol capable of providing a 3D realistic developmental map of the prenatal mouse knee joint was designed by combining Optical Projection Tomography imaging (OPT) and a deformable registration algorithm (Sheffield Image Registration toolkit, ShIRT). Eleven left limbs of healthy murine embryos were scanned with OPT (voxel size: 14.63μm) at two different stages of development: Theiler stage (TS) 23 (approximately 14.5 embryonic days) and 24 (approximately 15.5 embryonic days). One TS23 limb was used to evaluate the precision of the displacement predictions for this specific case. The remaining limbs were then used to estimate Developmental Tibia and Femur Maps. Acceptable uncertainties of the displacement predictions computed from repeated images were found for both epiphyses (between 1.3μm and 1.4μm for the proximal tibia and between 0.7μm and 1.0μm for the femur, along all directions). The protocol was found to be reproducible with maximum Modified Housdorff Distance (MHD) differences equal to 1.9 μm and 1.5 μm for the tibial and femoral epiphyses respectively. The effect of the initial shape of the rudiment affected the developmental maps with MHD of 21.7 μm and 21.9 μm for the tibial and femoral epiphyses respectively, which correspond to 1.4 and 1.5 times the voxel size. To conclude, this study proposes a repeatable semi-automatic protocol capable of providing mean 3D realistic developmental map of a developing rudiment allowing researchers to study how growth and adaptation are directed by biological and mechanobiological factors.

Highlights

Growth and morphogenesis are two fundamental processes which every living system undergo during both the prenatal and juvenile phase
The aim of this study was to develop a repeatable semi-automatic protocol capable of providing a 3D realistic developmental map of the tibial and femoral developing rudiments in a prenatal mouse model. This was achieved by combining Optical Projection Tomography imaging (OPT) imaging [21] and the deformable registration algorithm ShIRT [18,19,20]
The process of joint morphogenesis is key for physiological skeletal development

Summary

Introduction

Growth and morphogenesis are two fundamental processes which every living system undergo during both the prenatal and juvenile phase. Joint morphogenesis is the key process through which the two opposing cartilaginous rudiments of a joint develop their reciprocal and fully functional shapes, and which starts during prenatal joint development. Mechanobiological growth models have been used to deepen our understanding on morphogenesis by exploring the role of motion or loading on joint shape [5, 12,13,14,15]. Despite their undeniable importance these models have a series of limitations. Due to a lack of information, the cascade of biochemical factors determining the amount of biological growth on which the mechanical stimuli operates were extremely simplified and considered to be proportional to the chondrocytes density in the region of interest [12, 13]

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