In Vivo and Clinical

In Vivo and Clinical consists of two workpackages, Work Package 7. Animal Study and WP8. Clinical Study.MultiSim Flow Chart 2 In Vivo and Clinical 2-01Work Package 7. Animal Study

WP Leader: Dr Enrico Dall’Ara

“Animal studies will allow us to challenge the prediction ability of our computation models in each subject in vivo, and therefore to improve our understanding of the link between cell, tissue and organ levels”

Animal models can be used to obtain missing information not available in humans and to quantitatively validate the computational models. The models created in this WP will be based on the ones developed in the other work packages and adapted for mice bones, in particular for the tissue and organ levels. The developed models based on state of the art imaging techniques will be challenged in predicting induced bone resorption and bone apposition. Ovariectomy or castration procedures will be used in order to study local and systemic regulators of bone resorption and morphological changes. Mice will be allowed to lose bone for 2-4 weeks. To model physiological increases in bone mass, non-invasive application of mechanical loads to the tibia will be performed on alternate days in a 2-week period. Drug treatments to moderate these effects will include bisphosphonates (to inhibit bone loss) and PTH to stimulate bone accrual.

The WP7 has started only in the second year of the project and, therefore, the preliminary data are mainly related to the work done in parallel projects. An in vivo microCT scanning procedure has been developed in order to scan the mouse tibia of the same mouse longitudinally. In approximately 30 minutes time we can scan the whole tibia and fibula with high resolution (10 microns voxel size) and measure trabecular and cortical densitometric and morphometric parameters. The reduction of scanning time and radiation dose will be investigated during the next months. A loading model for the mice tibia has been developed in Prof Tim Skerry’s group where both tibia and fibula are loaded repeatedly. From preliminary data bone apposition has been seen by means of microCT ex vivo. Now we are replicating this approach to track the changes in the same bone of the sample animal in vivo.

With WP4 (tissue level). The procedures currently defined in WP4 for developing models of cortical and trabecular bone for human tissue are used in order to create models at the organ level for the mice bones. In particular, similar microFE approach will be used in order to convert high resolution microCT images into large hexahedral mesh models. With WP5 (cell level). The experimental part of WP7 will be integrated to the analysis of the RNA in order to explore different gene expression in loaded and not loaded bones.

Work Package 8. Clinical Study

WP Leader: Professor Eugene McCloskey

The objective of this WP is to gather clinical data for the WP1-5 and to test the multiscale hypermodelling framework within a clinical context. A number of subjects (including fallers and non-fallers) will be recruited to form a complete database of potential clinical imaging and functional assessments that will be made available for all WPs.

For these subjects gait analysis (WP2) will be performed in the lab while sensors in their home developed in WP1 will be used for a short period of time (1 week). QCT and MRI of the lower limb will be obtained to obtain bone, cartilage, ligament and muscle information (geometry and pixel-intensity related information).