A novel framework for elucidating the effect of mechanical loading on the geometry of ovariectomized mouse tibiae using principal component analysis

Introduction: Murine models are used to test the effect of anti-osteoporosis treatments as they replicate some of the bone phenotypes observed in osteoporotic (OP) patients. The effect of disease and treatment is typically described as changes in bone geometry and microstructure over time. Conventional assessment of geometric changes relies on morphometric scalar parameters. However, being correlated with each other, these parameters do not describe separate fractions of variations and offer only a moderate insight into temporal changes.

Methods: The current study proposes a novel image-based framework that employs deformable image registration on in vivo longitudinal images of bones and Principal Component Analysis (PCA) for improved quantification of geometric effects of OP treatments. This PCA-based model and a novel post-processing of score changes provide orthogonal modes of shape variations temporally induced by a course of treatment (specifically in vivo mechanical loading).

Results and Discussion: Errors associated with the proposed framework are rigorously quantified and it is shown that the accuracy of deformable image registration in capturing the bone shapes (∼1 voxel = 10.4 μm) is of the same order of magnitude as the relevant state-of-the-art evaluation studies. Applying the framework to longitudinal image data from the midshaft section of ovariectomized mouse tibia, two mutually orthogonal mode shapes are reliably identified to be an effect of treatment. The mode shapes captured changes of the tibia geometry due to the treatment at the anterior crest (maximum of 0.103 mm) and across the tibia midshaft section and the posterior (0.030 mm) and medial (0.024 mm) aspects. These changes agree with those reported previously but are now described in a compact fashion, as a vector field of displacements on the bone surface. The proposed framework enables a more detailed investigation of the effect of disease and treatment on bones in preclinical studies and boosts the precision of such assessments.