Non-Invasive Prediction of Bone Mechanical Properties of the Mouse Tibia in Longitudinal Preclinical Studies

The mouse tibia is a common site to investigate bone remodelling and the effect of treatments preclinically. It can be monitored using in vivo micro-Computed Tomography (microCT) imaging in order to track longitudinal changes in its morphometric and densitometric properties. Additionally, microCT images can be converted into micro-Finite Element (microFE) models for the non-invasive estimation of mechanical properties. Therefore, the combination of in vivo imaging and microFE modelling can provide comprehensive analyses about bone changes over space and time. However, repeated ionizing radiation exposure can have a significant effect on the bone properties; also, microFE models need to be validated against experimental measurements before application. The aim of this PhD project was to provide the best practice for the definition and validation of the in vivo microCT scanning procedure for the mouse tibia in preclinical studies. First, different scanning protocols have been tested by quantifying the accuracy of the image-based measurements against high resolution scans. One of the procedures has been selected as the best compromise between measurement accuracy and nominal radiation dose. Afterwards, microFE predictions of local and structural mechanical properties obtained using the selected scanning protocol have been validated. The experimental data for the validation has been obtained using the Digital Volume Correlation (DVC) approach, the only method which can provide volumetric measurements of local displacements under loading. Good to excellent correlations between the measured and predicted displacements were found. Errors in predictions of structural properties were in the order of 10-15%. Lastly, the protocol has been tested in vivo. The right tibia of 24 mice has been scanned in vivo five times, while the left tibia has been used as non-irradiated control. Non-significant or minimal radiation effects were found on the morphometric, densitometric and mechanical properties of the tibia. In conclusion, a scanning procedure for longitudinal in vivo microCT imaging of the whole mouse tibia has been defined and validated. The protocol will be used in future studies for investigating the effect of bone interventions.

Year	Entry
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Year

Entry

2011

Tassani S, Öhman C, Baruffaldi F, Baleani M, Viceconti M. Volume to density relation in adult human bone tissue. J Biomech. 2011;44(1):103-108.

2002

Nuzzo S, Peyrin F, Cloetens P, Baruchel J, Boivin G. Quantification of the degree of mineralization of bone in three dimensions using synchrotron radiation microtomography. Med Phys. November 2002;29(11):2672-2681.

2013

Weatherholt AM, Fuchs RK, Warden SJ. Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model. Bone. January 2013;52(1):372-379.

2008

Webster DJ, Morley PL, van Lenthe GH, Müller R. A novel in vivo mouse model for mechanically stimulated bone adaptation: a combined experimental and computational validation study. Comput Methods Biomech Biomed Eng. October 2008;11(5):435-441.

2007

Anderson AE, Ellis BJ, Weiss JA. Verification, validation and sensitivity studies in computational biomechanics. Comput Methods Biomech Biomed Eng. June 2007;10(3):171-184.