Prediction of the 3D shape of the L1 vertebral body from adjacent vertebrae.

The aim of treatments of vertebral fractures is the anatomical reduction to restore the physiological biomechanics of the spine and the stabilization of the fracture to allow bone healing. However, the three-dimensional shape of the fractured vertebral body before the fracture is unknown in the clinical setting. Information about the pre-fracture vertebral body shape could help surgeons to select the optimal treatment. The goal of this study was to develop and validate a method based on Singular Value Decomposition (SVD) to predict the shape of the vertebral body of L1 from the shapes of T12 and L2. The geometry of the vertebral bodies of T12, L1 and L2 vertebrae of 40 patients were extracted from CT scans available from the VerSe2020 open-access dataset. Surface triangular meshes of each vertebra were morphed onto a template mesh. The set of vectors with the node coordinates of the morphed T12, L1 and L2 were compressed with SVD and used to build a system of linear equations. This system was used to solve a minimization problem and to reconstruct the shape of L1. A leave-one-out cross-validation was performed. Moreover, the approach was tested against an independent dataset with large osteophytes. The results of the study show a good prediction of the shape of the vertebral body of L1 from the shapes of the two adjacent vertebrae (mean error equal to 0.51 ± 0.11 mm on average, Hausdorff distance equal to 2.11 ± 0.56 mm on average), compared to current CT resolution typically used in the operating room. The error was slightly higher for patients presenting large osteophytes or severe bone degeneration (mean error equal to 0.65 ± 0.10 mm, Hausdorff distance equal to 3.54 ± 1.03 mm). The accuracy of the prediction was significantly better than approximating the shape of the vertebral body of L1 by the shape of T12 or L2. This approach could be used in the future to improve the pre-planning of spine surgeries to treat vertebral fractures.

A practical guide for in situ mechanical testing of musculoskeletal tissues using synchrotron tomography.

Musculoskeletal tissues are complex hierarchical materials where mechanical response is linked to structural and material properties at different dimensional levels. Therefore, high-resolution three-dimensional tomography is very useful for assessing tissue properties at different scales. In particular, Synchrotron Radiation micro-Computed Tomography (SR-microCT) has been used in several applications to analyze the structure of bone and biomaterials. In the past decade the development of digital volume correlation (DVC) algorithms applied to SR-microCT images and its combination with in situ mechanical testing (four-dimensional imaging) have allowed researchers to visualise, for the first time, the deformation of musculoskeletal tissues and their interaction with biomaterials under different loading scenarios. However, there are several experimental challenges that make these measurements difficult and at high risk of failure. Challenges relate to sample preparation, imaging parameters, loading setup, accumulated tissue damage for multiple tomographic acquisitions, reconstruction methods and data processing. Considering that access to SR-microCT facilities is usually associated with bidding processes and long waiting times, the failure of these experiments could notably slow down the advancement of this research area and reduce its impact. Many of the experimental failures can be avoided with increased experience in performing the tests and better guidelines for preparation and execution of these complex experiments; publication of negative results could help interested researchers to avoid recurring mistakes. Therefore, the goal of this article is to highlight the potential and pitfalls in the design and execution of in situ SR-microCT experiments, involving multiple scans, of musculoskeletal tissues for the assessment of their structural and/or mechanical properties. The advice and guidelines that follow should improve the success rate of this type of experiment, allowing the community to reach higher impact more efficiently.

Accuracy of in vivo microCT imaging in assessing the microstructural properties of the mouse tibia subchondral bone.

Osteoarthritis (OA) is one of the most common musculoskeletal diseases. OA is characterized by degeneration of the articular cartilage as well as the underlying subchondral bone. Post-traumatic osteoarthritis (PTOA) is a subset of OA caused by mechanical trauma. Mouse models, such as destabilization of the medial meniscus (DMM), are useful to study PTOA. Ex vivo micro-Computed Tomography (microCT) imaging is the predominant technique used to scan the mouse knee in OA studies. Nevertheless, in vivo microCT enables the longitudinal assessment of bone microstructure, reducing measurement variability and number of animals required. The effect of image resolution in measuring subchondral bone parameters was previously evaluated only for a limited number of parameters. The aim of this study was to evaluate the ability of in vivo microCT imaging in measuring the microstructural properties of the mouse tibia trabecular and cortical subchondral bone, with respect to ex vivo high resolution imaging, in a DMM model of PTOA. Sixteen male C57BL/6J mice received DMM surgery or sham operation at 14 weeks of age (N=8 per group). The right knee of each mouse was microCT scanned in vivo (10.4µm voxel size) and ex vivo (4.35µm voxel size) at the age of 26 weeks. Each image was aligned to a reference image using rigid registration. The subchondral cortical bone plate thickness was measured at the lateral and medial condyles. Standard morphometric parameters were measured in the subchondral trabecular bone. In vivo microCT imaging led to significant underestimation of bone volume fraction (-14%), bone surface density (-3%) and trabecular number (-16%), whereas trabecular thickness (+3%) and separation (+5%) were significantly overestimated. Nevertheless, most trabecular parameters measured in vivo were well correlated with ex vivo measurements (R2 = 0.69-0.81). Degree of anisotropy, structure model index and connectivity density were measured in vivo with lower accuracy. Excellent accuracy was found for cortical thickness measurements. In conclusion, this study identified what bone morphological parameters can be reliably measured by in vivo microCT imaging of the subchondral bone in the mouse tibia. It highlights that this approach can be used to study longitudinal effects of diseases and treatments on the subchondral cortical bone and on most subchondral trabecular bone parameters, but systematic over- or under-estimations should be considered when interpreting the results.

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1.

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. METHOD: A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. RESULTS: 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. CONCLUSIONS: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Non-invasive prediction of the mouse tibia mechanical properties from microCT images: comparison between different finite element models.

New treatments for bone diseases require testing in animal models before clinical translation, and the mouse tibia is among the most common models. In vivo micro-Computed Tomography (microCT)-based micro-Finite Element (microFE) models can be used for predicting the bone strength non-invasively, after proper validation against experimental data. Different modelling techniques can be used to estimate the bone properties, and the accuracy associated with each is unclear. The aim of this study was to evaluate the ability of different microCT-based microFE models to predict the mechanical properties of the mouse tibia under compressive load. Twenty tibiae were microCT scanned at 10.4 µm voxel size and subsequently compressed at 0.03 mm/s until failure. Stiffness and failure load were measured from the load-displacement curves. Different microFE models were generated from each microCT image, with hexahedral or tetrahedral mesh, and homogeneous or heterogeneous material properties. Prediction accuracy was comparable among models. The best correlations between experimental and predicted mechanical properties, as well as lower errors, were obtained for hexahedral models with homogeneous material properties. Experimental stiffness and predicted stiffness were reasonably well correlated (R2 = 0.53-0.65, average error of 13-17%). A lower correlation was found for failure load (R2 = 0.21-0.48, average error of 9-15%). Experimental and predicted mechanical properties normalized by the total bone mass were strongly correlated (R2 = 0.75-0.80 for stiffness, R2 = 0.55-0.81 for failure load). In conclusion, hexahedral models with homogeneous material properties based on in vivo microCT images were shown to best predict the mechanical properties of the mouse tibia.

Optimization of the failure criterion in micro-Finite Element models of the mouse tibia for the non-invasive prediction of its failure load in preclinical applications.

New treatments against osteoporosis require testing in animal models and the mouse tibia is among the most common studied anatomical sites. In vivo micro-Computed Tomography (microCT) based micro-Finite Element (microFE) models can be used for predicting the bone strength non-invasively, after proper validation against experiments. The aim of this study was to evaluate the ability of different microCT-based bone parameters and microFE models to predict tibial structural mechanical properties in compression. Twenty tibiae were scanned at 10.4 µm voxel size and subsequently tested in uniaxial compression at 0.03 mm/s until failure. Stiffness and failure load were measured from the load-displacement curves. Standard morphometric parameters were measured from the microCT images. The spatial distribution of bone mineral content (BMC) was evaluated by dividing the tibia into 40 regions. MicroFE models were generated by converting each microCT image into a voxel-based mesh with homogeneous isotropic material properties. Failure load was estimated by using different failure criteria, and the optimized parameters were selected by minimising the errors with respect to experimental measurements. Experimental and predicted stiffness were moderately correlated (R2 = 0.65, error = 14% ± 8%). Normalized failure load was best predicted by microFE models (R2 = 0.81, error = 9% ± 6%). Failure load was not correlated to the morphometric parameters and weakly correlated with some geometrical parameters (R2 < 0.37). In conclusion, microFE models can improve the current estimation of the mouse tibia structural properties and in this study an optimal failure criterion has been defined. Since it is a non-invasive method, this approach can be applied longitudinally for evaluating temporal changes in the bone strength.

Effect of size and location of simulated lytic lesions on the structural properties of human vertebral bodies, a micro-finite element study.

Currently, the Spinal Instability Neoplastic Score system is used in clinics to evaluate the risk of fracture in patients with spinal metastases. This method, however, does not always provide a clear guideline due to the complexity in accounting for the effect of metastatic lesions on vertebral stability. The aim of this study was to use a validated micro Finite Element (microFE) modelling approach to analyse the effect of the size and location of lytic metastases on the mechanical properties of human vertebral bodies. Micro Computed Tomography based microFE models were generated with and without lytic lesions simulated as holes within a human vertebral body. Single and multiple lytic lesions were simulated with four different sizes and in five different locations. Bone was assumed homogenous, isotropic and linear elastic, and each vertebra was loaded in axial compression. It was observed that the size of lytic lesions was linearly related with the reduction in structural properties of the vertebral body (reduction of stiffness between 3% and 30% for lesion volume between 4% and 35%). The location of lytic lesions did not show a clear effect on predicted structural properties. Single or multiple lesions with the same volume provided similar results. Locally, there was a homogeneous distribution of axial principal strains among the models with and without lytic lesions. This study highlights the potential of microFE models to study the effect of lesions on the mechanical properties of the human vertebral body.

A new approach to comprehensively evaluate the morphological properties of the human femoral head: example of application to osteoarthritic joint.

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 µm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone.

Biomechanical assessment of vertebrae with lytic metastases with subject-specific finite element models.

The assessment of risk of vertebral fracture in patients with lytic metastases is challenging, due to the complexity in modelling the mechanical properties of this heterogeneous material. Currently clinical assessment of patients at high risk of fracture is based on the Spinal Instability Neoplastic Score (SINS), which however in many cases does not provide clear guidelines. The goal of this study was to develop a computational approach to provide a comparative biomechanical assessment of vertebrae with lytic lesions with respect to the adjacent controls and highlight the critical vertebrae. The computed tomography images of the thoracolumbar spine of eight patients suffering of vertebral lytic metastases with SINS between 7 and 12 (indeterminate unstable) were analysed. For each patient one or two vertebrae with lytic lesions were modelled and the closest vertebrae without lesions were considered as control. Metastatic vertebrae (N = 12) and controls (N = 18) were converted to subject-specific, heterogeneous, isotropic, nonlinear finite element models for simulating uniaxial compression. Densitometric and mechanical properties were computed for each vertebra. In average, similar mechanical properties were found for vertebrae with lytic lesions and controls (e.g. ultimate force equal to 6.2 ±â€¯2.7 kN for vertebrae with lytic lesions and to 6.2 ±â€¯3.0 kN for control vertebrae). Only in three patients the vertebrae with lytic lesions were found to be mechanically weaker (-19% to -75% difference for ultimate stress) than the controls. In conclusion, in this study we presented an approach to estimate the mechanical competence of vertebrae with lytic metastases. It remains to be investigated in a clinical study if this method, together with the SINS, can better classify patients with vertebrae with lytic lesions at high risk of fracture.

Uncertainties of synchrotron microCT-based digital volume correlation bone strain measurements under simulated deformation.

Digital Volume Correlation (DVC) is used to measure internal displacements and strains in bone. Recent studies have shown that Synchrotron radiation micro-computed tomography (SR-microCT) can improve the accuracy and precision of DVC. However, only zero-strain or virtually-moved test have been used to quantify the DVC uncertainties, leading to potential underestimation of the measurement errors. In this study, for the first time, the uncertainties of a global DVC approach have been evaluated on repeated SR-microCT scans of bovine cortical bone (voxel size: 1.6 µm), which were virtually deformed for different magnitudes and along different directions. The results showed that systematic and random errors of the normal strain components along the deformation direction were higher than the errors along unstrained directions. The systematic percentage errors were smaller for larger virtual deformations. The random percentage error was in the order of 10% of the virtual deformation. However, higher errors were localized at the boundary of the volumes of interest, perpendicular to the deformation direction. When only the central region of the samples was considered (100 µm layers removed from the borders where the deformation was applied), the errors in the direction of virtual deformation were comparable to the errors in the unstrained directions. In conclusion, the method presented to estimate the uncertainties of DVC is suitable for testing anisotropic specimens as cortical bone. The good agreement between the uncertainties in measurements of strain components obtained with this approach and with the simpler zero-strain-test suggests that the latter is adequate in the tested deformation scenarios.

Variability in strain distribution in the mice tibia loading model: A preliminary study using digital volume correlation.

It is well known that bone has an enormous adaptive capacity to mechanical loadings, and to this extent, several in vivo studies on mouse tibia use established cyclic compressive loading protocols to investigate the effects of mechanical stimuli. In these experiments, the applied axial load is well controlled but the positioning of the hind-limb between the loading endcaps may dramatically affect the strain distribution induced on the tibia. In this study, the full field strain distribution induced by a typical in vivo setup on mouse tibiae was investigated through a combination of in situ compressive testing, µCT scanning and a global digital volume correlation (DVC) approach. The precision of the DVC method and the effect of repositioning on the strain distributions were evaluated. Acceptable uncertainties of the DVC approach for the analysis of loaded tibiae (411 ± 58µÉ›) were found for nodal spacing of approximately 50 voxels (520 µm). When pairs of in situ preloaded and loaded images were registered, low variability of the strain distributions within the tibia were seen (range of mean differences in principal strains: 585-1800µÉ›). On contrary, larger differences were seen after repositioning (range of mean differences in principal strains: 2500-5500µÉ›). To conclude, these preliminary results on thee specimens showed that the DVC approach applied to the mouse tibia can be precise enough to evaluate local strain distributions under loads, and that repositioning of the hind-limb within the testing machine can induce large differences in the strain distributions that should be accounted for when modelling this system.

Mapping anisotropy improves QCT-based finite element estimation of hip strength in pooled stance and side-fall load configurations.

Hip fractures are one of the most severe consequences of osteoporosis. Compared to the clinical standard of DXA-based aBMD at the femoral neck, QCT-based FEA delivers a better surrogate of femoral strength and gains acceptance for the calculation of hip fracture risk when a CT reconstruction is available. Isotropic, homogenised voxel-based, finite element (hvFE) models are widely used to estimate femoral strength in cross-sectional and longitudinal clinical studies. However, fabric anisotropy is a classical feature of the architecture of the proximal femur and the second determinant of the homogenised mechanical properties of trabecular bone. Due to the limited resolution, fabric anisotropy cannot be derived from clinical CT reconstructions. Alternatively, fabric anisotropy can be extracted from HR-pQCT images of cadaveric femora. In this study, fabric anisotropy from HR-pQCT images was mapped onto QCT-based hvFE models of 71 human proximal femora for which both HR-pQCT and QCT images were available. Stiffness and ultimate load computed from anisotropic hvFE models were compared with previous biomechanical tests in both stance and side-fall configurations. The influence of using the femur-specific versus a mean fabric distribution on the hvFE predictions was assessed. Femur-specific and mean fabric enhance the prediction of experimental ultimate force for the pooled, i.e. stance and side-fall, (isotropic: r2=0.81, femur-specific fabric: r2=0.88, mean fabric: r2=0.86,p<0.001) but not for the individual configurations. Fabric anisotropy significantly improves bone strength prediction for the pooled configurations, and mapped fabric provides a comparable prediction to true fabric. The mapping of fabric anisotropy is therefore expected to help generate more accurate QCT-based hvFE models of the proximal femur for personalised or multiple load configurations.

Validation of finite element models of the mouse tibia using digital volume correlation.

The mouse tibia is a common site to investigate bone adaptation. Micro-Finite Element (microFE) models based on micro-Computed Tomography (microCT) images can estimate bone mechanical properties non-invasively but their outputs need to be validated with experiments. Digital Volume Correlation (DVC) can provide experimental measurements of displacements over the whole bone volume. In this study we applied DVC to validate the local predictions of microFE models of the mouse tibia in compression. Six mouse tibiae were stepwise compressed within a microCT system. MicroCT images were acquired in four configurations with applied compression of 0.5 N (preload), 6.5 N, 13.0 N and 19.5 N. Failure load was measured after the last scan. A global DVC algorithm was applied to the microCT images in order to obtain the displacement field over the bone volume. Homogeneous, isotropic linear hexahedral microFE models were generated from the images collected in the preload configuration with boundary conditions interpolated from the DVC displacements at the extremities of the tibia. Experimental displacements from DVC and numerical predictions were compared at corresponding locations in the middle of the bone. Stiffness and strength were also estimated from each model and compared with the experimental measurements. The magnitude of the displacement vectors predicted by microFE models was highly correlated with experimental measurements (R2 >0.82). Higher but still reasonable errors were found for the Cartesian components. The models tended to overestimate local displacements in the longitudinal direction (R2 = 0.69-0.90, slope of the regression line=0.50-0.97). Errors in the prediction of structural mechanical properties were 14% ±â€¯11% for stiffness and 9% ±â€¯9% for strength. In conclusion, the DVC approach has been applied to the validation of microFE models of the mouse tibia. The predictions of the models for both structural and local properties have been found reasonable for most preclinical applications.

Comparison of HR-pQCT- and microCT-based finite element models for the estimation of the mechanical properties of the calcaneus trabecular bone.

The calcaneus bone is formed of extensive trabecular bone and is therefore well suited to be used as an example of loaded bone to establish the ability of combining microfinite element (microFE) technique with high-resolution peripheral quantitative computed tomography (HR-pQCT) in determining its mechanical properties. HR-pQCT is increasingly used as a tool for in vivo bone clinical research, but its use has been limited to the distal radius and tibia. The goal of this study was to determine the applicability of HR-pQCT-derived microFE models of the calcaneus trabecular bone with 82 µm voxel size with reference to higher-resolution microCT-based models taken as gold standard. By comparing the outputs of microFE models generated from both HR-pQCT and microCT images of the trabecular bone of five calcaneus cadaveric specimens, it was found that the HR-pQCT-based models predicted mechanical properties for fracture load, total reaction force and von Mises stress are considerably different from microCT-based counterparts by 33, 64 and 70%, respectively. Also, the morphological analysis showed a comprehensive geometrical difference between HR-pQCT-based microFE models and their microCT-based equivalents. The results of the HR-pQCT-based models were found to have strong dependency on the threshold value chosen to binarise the images prior to finite element modelling. In addition, it was found that the voxel size has a strong impact on accuracy of imaged-based microFE models compared to other factors such as the presence of soft tissue and image scanning integration time. Therefore, although HR-pQCT has shown to be useful to predict overall structural and biomechanical changes, it is limited in providing local accurate biomechanical properties of trabecular bone and therefore should be used with caution when assessing bone remodelling through local changes of trabecular bone apposition and resorption in disease treatment monitoring.

Effect of integration time on the morphometric, densitometric and mechanical properties of the mouse tibia.

Micro-Computed Tomography (microCT) images are used to measure morphometric and densitometric properties of bone, and to develop finite element (FE) models to estimate mechanical properties. However, there are concerns about the invasiveness of microCT imaging due to the X-rays ionising radiation induced by the repeated scans on the same animal. Therefore, the best compromise between radiation dose and image quality should be chosen for each preclinical application. In this study, we investigated the effect of integration time (time the bone is exposed to radiation at each rotation step during microCT imaging) on measurements performed on the mouse tibia. Four tibiae were scanned at 10.4 µm voxel size using four different procedures, characterized by decreasing integration time (from 200 ms to 50 ms) and therefore decreasing nominal radiation dose (from 513 mGy to 128 mGy). From each image, trabecular and cortical morphometric parameters, spatial distribution of bone mineral content (BMC) in the whole tibia and FE-based estimations of stiffness and strength were obtained. A high-resolution scan (4.3 µm voxel size) was used to quantify measurement errors. Integration time had the largest effect on trabecular morphometric parameters (7-28%). Lower effects were observed on cortical parameters (1-3%), BMC (1-10%) distribution, and FE-based estimations of mechanical properties (1-3%). In conclusion, the effect of integration time on image-based measurements has been quantified. This data should be considered when defining the in vivo microCT scanning protocols in order to find the best compromise between nominal radiation exposure and accuracy in the estimation of bone parameters.

Rotational stability in screw-fixed scaphoid fractures compared to plate-fixed scaphoid fractures.

BACKGROUND: The literature describes the treatment of scaphoid fractures comparing the volar and dorsal approaches, the advantages and disadvantages of percutaneous screw fixation, as well as the treatment of scaphoid nonunions using different types of cancellous or corticocancellous bone grafts. Yet, to date no studies are available comparing the outcome of rotational stability in screw-fixed scaphoid fractures to angular stable systems. The purpose of this study is to provide reliable data about rotational stability in stabilised scaphoid fractures and to gain information about the rigidity and the stability of the different types of fixation. METHODS: Three groups of different stabilisation methods on standardised scaphoid B2 fractures were tested for rotational stability. Stabilisation was achieved using one or two cannulated compression screws (CCS) or angular stable plating. We performed ten repetitive cycles up to 10°, 20° and 30° rotation, measuring the maximum torque and the average dissipated work at angle level. RESULTS: Our study showed that rotational stability using a two CCS fixation is significantly (p < 0.05) higher than single CCS fixation. Using the angular stable plate system was also superior to the single CCS (p < 0.05). There was, however, no significant difference between two CCS fixation and angular stable plate fixation. CONCLUSION: Even though indications of using screws or plate systems might be different and plate osteosynthesis may be preferable in treatment of dislocated or comminuted fractures as well as for nonunions, our study showed a better rotational stability by choosing more than just one screw for osteosynthesis. Angular stable plating of scaphoid fractures also provides more rotational stability than single CCS fixation. The authors therefore hypothesise higher union rates in scaphoid fractures using more stable fixation systems.

Longitudinal imaging of the ageing mouse.

Several non-invasive imaging techniques are used to investigate the effect of pathologies and treatments over time in mouse models. Each preclinical in vivo technique provides longitudinal and quantitative measurements of changes in tissues and organs, which are fundamental for the evaluation of alterations in phenotype due to pathologies, interventions and treatments. However, it is still unclear how these imaging modalities can be used to study ageing with mice models. Almost all age related pathologies in mice such as osteoporosis, arthritis, diabetes, cancer, thrombi, dementia, to name a few, can be imaged in vivo by at least one longitudinal imaging modality. These measurements are the basis for quantification of treatment effects in the development phase of a novel treatment prior to its clinical testing. Furthermore, the non-invasive nature of such investigations allows the assessment of different tissue and organ phenotypes in the same animal and over time, providing the opportunity to study the dysfunction of multiple tissues associated with the ageing process. This review paper aims to provide an overview of the applications of the most commonly used in vivo imaging modalities used in mouse studies: micro-computed-tomography, preclinical magnetic-resonance-imaging, preclinical positron-emission-tomography, preclinical single photon emission computed tomography, ultrasound, intravital microscopy, and whole body optical imaging.

Experimental validation of DXA-based finite element models for prediction of femoral strength.

Osteoporotic fractures are a major clinical problem and current diagnostic tools have an accuracy of only 50%. The aim of this study was to validate dual energy X-rays absorptiometry (DXA)-based finite element (FE) models to predict femoral strength in two loading configurations. Thirty-six pairs of fresh frozen human proximal femora were scanned with DXA and quantitative computed tomography (QCT). For each pair one femur was tested until failure in a one-legged standing configuration (STANCE) and one by replicating the position of the femur in a fall onto the greater trochanter (SIDE). Subject-specific 2D DXA-based linear FE models and 3D QCT-based nonlinear FE models were generated for each specimen and used to predict the measured femoral strength. The outcomes of the models were compared to standard DXA-based areal bone mineral density (aBMD) measurements. For the STANCE configuration the DXA-based FE models (R(2)=0.74, SEE=1473N) outperformed the best densitometric predictor (Neck_aBMD, R(2)=0.66, SEE=1687N) but not the QCT-based FE models (R(2)=0.80, SEE=1314N). For the SIDE configuration both QCT-based FE models (R(2)=0.85, SEE=455N) and DXA neck aBMD (R(2)=0.80, SEE=502N) outperformed DXA-based FE models (R(2)=0.77, SEE=529N). In both configurations the DXA-based FE model provided a good 1:1 agreement with the experimental data (CC=0.87 for SIDE and CC=0.86 for STANCE), with proper optimization of the failure criteria. In conclusion we found that the DXA-based FE models are a good predictor of femoral strength as compared with experimental data ex vivo. However, it remains to be investigated whether this novel approach can provide good predictions of the risk of fracture in vivo.

Estimation of local anisotropy of plexiform bone: Comparison between depth sensing micro-indentation and Reference Point Indentation.

The recently developed Reference Point Indentation (RPI) allows the measurements of bone properties at the tissue level in vivo. The goal of this study was to compare the local anisotropic behaviour of bovine plexiform bone measured with depth sensing micro-indentation tests and with RPI. Fifteen plexiform bone specimens were extracted from a bovine femur and polished down to 0.05µm alumina paste for indentations along the axial, radial and circumferential directions (N=5 per group). Twenty-four micro-indentations (2.5µm in depth, 10% of them were excluded for testing problems) and four RPI-indentations (~50µm in depth) were performed on each sample. The local indentation modulus Eind was found to be highest for the axial direction (24.3±2.5GPa) compared to the one for the circumferential indentations (19% less stiff) and for the radial direction (30% less stiff). RPI measurements were also found to be dependent on indentation direction (p<0.001) with the exception of the Indentation Distance Increase (IDI) (p=0.173). In particular, the unloading slope US1 followed similar trends compared to the Eind: 0.47±0.03N/µm for axial, 11% lower for circumferential and 17% lower for radial. Significant correlations were found between US1 and Eind (p=0.001; R(2)=0.58), while no significant relationship was found between IDI and any of the micro-indentation measurements (p>0.157). In conclusion some of the RPI measurements can provide information about local anisotropy but IDI cannot. Moreover, there is a linear relationship between most local mechanical properties measured with RPI and with micro-indentations, but IDI does not correlate with any micro-indentation measurements.

About the inevitable compromise between spatial resolution and accuracy of strain measurement for bone tissue: a 3D zero-strain study.

The accurate measurement of local strain is necessary to study bone mechanics and to validate micro computed tomography (µCT) based finite element (FE) models at the tissue scale. Digital volume correlation (DVC) has been used to provide a volumetric estimation of local strain in trabecular bone sample with a reasonable accuracy. However, nothing has been reported so far for µCT based analysis of cortical bone. The goal of this study was to evaluate accuracy and precision of a deformable registration method for prediction of local zero-strains in bovine cortical and trabecular bone samples. The accuracy and precision were analyzed by comparing scans virtually displaced, repeated scans without any repositioning of the sample in the scanner and repeated scans with repositioning of the samples. The analysis showed that both precision and accuracy errors decrease with increasing the size of the region analyzed, by following power laws. The main source of error was found to be the intrinsic noise of the images compared to the others investigated. The results, once extrapolated for larger regions of interest that are typically used in the literature, were in most cases better than the ones previously reported. For a nodal spacing equal to 50 voxels (498 µm), the accuracy and precision ranges were 425-692 µÎµ and 202-394 µÎµ, respectively. In conclusion, it was shown that the proposed method can be used to study the local deformation of cortical and trabecular bone loaded beyond yield, if a sufficiently high nodal spacing is used.