Mapping anisotropy of the proximal femur for enhanced image based finite element analysis

Finite element (FE) models of bone derived from quantitative computed tomography (QCT) rely on realistic material properties to accurately predict bone strength. QCT cannot resolve bone microarchitecture, therefore QCT-based FE models lack the anisotropy apparent within the underlying bone tissue. This study proposes a method for mapping femoral anisotropy using high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of human cadaver specimens. Femur HR-pQCT images were sub-divided into numerous overlapping cubic sub-volumes and the local anisotropy was quantified using a ‘direct-mechanics’ method. The resulting directionality reflected all the major stress lines visible within the trabecular lattice, and provided a realistic estimate of the alignment of Harvesian systems within the cortical compartment. QCT-based FE models of the proximal femur were constructed with isotropic and anisotropic material properties, with directionality interpolated from the map of anisotropy. Models were loaded in a sideways fall configuration and the resulting whole bone stiffness was compared to experimental stiffness and ultimate strength. Anisotropic models were consistently less stiff, but no statistically significant differences in correlation were observed between material models against experimental data. The mean difference in whole bone stiffness between model types was approximately 26%, suggesting that anisotropy can still effect considerable change in the mechanics of proximal femur models. The under prediction of whole bone stiffness in anisotropic models suggests that the orthotropic elastic constants require further investigation. The ability to map mechanical anisotropy from high-resolution images and interpolate information into clinical-resolution models will allow testing of new anisotropic material mapping strategies.     

Concept and development of an orthotropic FE model of the proximal femur

PURPOSE: In contrast to many isotropic finite-element (FE) models of the femur in literature, it was the object of our study to develop an orthotropic FE "model femur" to realistically simulate three-dimensional bone remodelling. METHODS: The three-dimensional geometry of the proximal femur was reconstructed by CT scans of a pair of cadaveric femurs at equal distances of 2mm. These three-dimensional CT models were implemented into an FE simulation tool. Well-known "density-determined" bony material properties (Young's modulus; Poisson's ratio; ultimate strength in pressure, tension and torsion; shear modulus) were assigned to each FE of the same "CT-density-characterized" volumetric group.In order to fix the principal directions of stiffness in FE areas with the same "density characterization", the cadaveric femurs were cut in 2mm slices in frontal (left femur) and sagittal plane (right femur). Each femoral slice was scanned into a computer-based image processing system. On these images, the principal directions of stiffness of cancellous and cortical bone were determined manually using the orientation of the trabecular structures and the Haversian system. Finally, these geometric data were matched with the "CT-density characterized" three-dimensional femur model. In addition, the time and density-dependent adaptive behaviour of bone remodelling was taken into account by implementation of Carter's criterion. RESULTS: In the constructed "model femur", each FE is characterized by the principal directions of the stiffness and the "CT-density-determined" material properties of cortical and cancellous bone. Thus, on the basis of anatomic data a three-dimensional FE simulation reference model of the proximal femur was realized considering orthotropic conditions of bone behaviour. CONCLUSIONS: With the orthotropic "model femur", the fundamental basis has been formed to realize realistic simulations of the dynamical processes of bone remodelling under different loading conditions or operative procedures (osteotomies, total hip replacements, etc).     

Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia

IntroductionPreviously, a finite element (FE) model of the proximal tibia was developed and validated against experimentally measured local subchondral stiffness. This model indicated modest predictions of stiffness (R² = 0.77, normalized root mean squared error (RMSE%) = 16.6%). Trabecular bone though was modeled with isotropic material properties despite its orthotropic anisotropy. The objective of this study was to identify the anisotropic FE modeling approach which best predicted (with largest explained variance and least amount of error) local subchondral bone stiffness at the proximal tibia.MethodsLocal stiffness was measured at the subchondral surface of 13 medial/lateral tibial compartments using in situ macro indentation testing. An FE model of each specimen was generated assuming uniform anisotropy with 14 different combinations of cortical- and tibial-specific density-modulus relationships taken from the literature. Two FE models of each specimen were also generated which accounted for the spatial variation of trabecular bone anisotropy directly from clinical CT images using grey-level structure tensor and Cowin’s fabric-elasticity equations. Stiffness was calculated using FE and compared to measured stiffness in terms of R² and RMSE%.ResultsThe uniform anisotropic FE model explained 53–74% of the measured stiffness variance, with RMSE% ranging from 12.4 to 245.3%. The models which accounted for spatial variation of trabecular bone anisotropy predicted 76–79% of the variance in stiffness with RMSE% being 11.2–11.5%.ConclusionsOf the 16 evaluated finite element models in this study, the combination of Synder and Schneider (for cortical bone) and Cowin’s fabric-elasticity equations (for trabecular bone) best predicted local subchondral bone stiffness.     

Patient-specific finite-element analyses of the proximal femur with orthotropic material properties validated by experiments

Patient-specific high order finite-element (FE) models of human femurs based on quantitative computer tomography (QCT) with inhomogeneous orthotropic and isotropic material properties are addressed. The point-wise orthotropic properties are determined by a micromechanics (MM) based approach in conjunction with experimental observations at the osteon level, and two methods for determining the material trajectories are proposed (along organs outer surface, or along principal strains). QCT scans on four fresh-frozen human femurs were performed and high-order FE models were generated with either inhomogeneous MM-based orthotropic or empirically determined isotropic properties. In vitro experiments were conducted on the femurs by applying a simple stance position load on their head, recording strains on femurs' surface and head's displacements. After verifying the FE linear elastic analyses that mimic the experimental setting for numerical accuracy, we compared the FE results to the experimental observations to identify the influence of material properties on models' predictions. The strains and displacements computed by FE models having MM-based inhomogeneous orthotropic properties match the FE-results having empirically based isotropic properties well, and both are in close agreement with the experimental results. When only the strains in the femoral neck are being compared a more pronounced difference is noticed between the isotropic and orthotropic FE result. These results lay the foundation for applying more realistic inhomogeneous orthotropic material properties in FEA of femurs.     

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.     

An accurate estimation of bone density improves the accuracy of subject-specific finite element models

An experimental-numerical study was performed to investigate the relationships between computed tomography (CT)-density and ash density, and between ash density and apparent density for bone tissue, to evaluate their influence on the accuracy of subject-specific FE models of human bones. Sixty cylindrical bone specimens were examined. CT-densities were computed from CT images while apparent and ash densities were measured experimentally. The CT/ash-density and ash/apparent-density relationships were calculated. Finite element models of eight human femurs were generated considering these relationships to assess their effect on strain prediction accuracy. CT and ash density were linearly correlated (R(2)=0.997) over the whole density range but not equivalent (intercep t <0, slope >1). A constant ash/apparent-density ratio (0.598+/-0.004) was found for cortical bone. A lower ratio, with a larger dispersion, was found for trabecular bone (0.459+/-0.100), but it became less dispersed, and equal to that of cortical tissue, when testing smaller trabecular specimens (0.598+/-0.036). This suggests that an experimental error occurred in apparent-density measurements for large trabecular specimens and a constant ratio can be assumed valid for the whole density range. Introducing the obtained relationships in the FE modelling procedure improved strain prediction accuracy (R(2)=0.95, RMSE=7%). The results suggest that: (i) a correction of the densitometric calibration should be used when evaluating bone ash-density from clinical CT scans, to avoid ash-density underestimation and overestimation for low- and high-density bone tissue, respectively; (ii) the ash/apparent-density ratio can be assumed constant in human femurs and (iii) the correction improves significantly the model accuracy and should be considered in subject-specific bone modelling.     

Effects of damage on the orthotropic material symmetry of bovine tibial trabecular bone

The macroscopic mechanical properties of trabecular bone can be predicted by its architecture using theoretical relationships between the elastic and architectural properties. Microdamage caused by overloading or fatigue decreases the apparent elastic moduli of trabecular bone requiring these relationships to be modified to predict the damaged elastic properties. In the case of isotropic damage, the apparent level elastic properties could be determined by multiplying all of the elastic constants by a single scalar factor. If the damage is anisotropic, the elastic constants may change by differing factors and the material coordinate system could become misaligned with the fabric coordinate system. High-resolution finite element models were used to simulate damage overloading on seven trabecular bone specimens subjected to pure shear strain in two planes. Comparison of the apparent elastic moduli of the specimens before and after damage showed that the reduction of the elastic moduli was anisotropic. This suggests that the microdamage within the specimens was inhomogeneous. However, after damage the specimens exhibited nearly orthotropic material symmetry as they did before damage. Changes in the orientation of the orthotropic material coordinate system were also small and occurred primarily in the transverse plane. Thus, while damage in trabecular bone is anisotropic, the material coordinate system remains aligned with the fabric tensor.     

Quantification of trabecular spatial orientation from low-resolution images

No accepted methodology exists to assess trabecular bone orientation from clinical CT scans. The aim of this study was to test the hypothesis that the distribution of grey values in clinical CT images is related to the underlying trabecular architecture and that this distribution can be used to identify the principal directions and local anisotropy of trabecular bone. Fourteen trabecular bone samples were extracted from high-resolution (30 μm) micro-CT scans of seven human femoral heads. Trabecular orientations and local anisotropy were calculated using grey-level deviation (GLD), a novel method providing a measure of the three-dimensional distribution of image grey values. This was repeated for different image resolutions down to 300 μm and for volumes of interest (VOIs) ranging from 1 to 7 mm. Outcomes were compared with the principal mechanical directions and with mean intercept length (MIL) as calculated for the segmented 30-μm images. For the 30-μm images, GLD predicted the mechanical principal directions equally well as MIL. For the 300-μm images, which are resolutions that can be obtained in vivo using clinical CT, only a small increase (3°–6°) in the deviation from the mechanical orientations was found. VOIs of 5 mm resulted in a robust quantification of the orientation. We conclude that GLD can quantify structural bone parameters from low-resolution CT images.     

Comparison of micro-level and continuum-level voxel models of the proximal femur

Continuum-level finite element (FE) models became standard computational tools for the evaluation of bone mechanical behavior from in vivo computed tomography scans. Such scans do not account for the anisotropy of the bone. Instead, local mechanical properties in the continuum-level FE models are assumed isotropic and are derived from bone density, using statistical relationships. Micro-FE models, on the other hand, incorporate the anisotropic structure in detail. This study aimed to quantify the effects of assumed isotropy, by comparing continuum-level voxel models of a healthy and a severely osteoporotic proximal femur with recently analyzed micro-FE models of the same bones. The micro-model element size was coarsened to generate continuum FE models with two different element sizes (0.64 and 3.04 mm) and two different density–modulus relationships found in the literature for wet and ash density. All FE models were subjected to the same boundary conditions that simulated a fall to the side, and the stress and strain distributions, model stiffness and yield load were compared. The results indicated that the stress and strain distributions could be reproduced well with the continuum models. The smallest differences between the continuum-level model and micro-level model predictions of the stiffness and yield load were obtained with the coarsest element size. Better results were obtained for both continuum-element sizes when isotropic moduli were based on ash density rather than wet density.     

A global relationship between trabecular bone morphology and homogenized elastic properties.

An alternative concept of the relationship between morphological and elastic properties of trabecular bone is presented and applied to human tissue from several anatomical locations using a digital approach. The three-dimensional morphology of trabecular bone was assessed with a microcomputed tomography system and the method of directed secants as well as the star volume procedure were used to compute mean intercept length (MIL) and average bone length (ABL) of 4 mm cubic specimens. Assuming isotropic elastic properties for the trabecular tissue, the general elastic tensors of the bone specimens were determined using the homogenization method and the closest orthotropic tensors were calculated with an optimization algorithm. The assumption of orthotropy for trabecular bone was found to improve with specimen size and hold within 6.1 percent for a 4 mm cube size. A strong global relationship (r2 = 0.95) was obtained between fabric and the orthotropic elastic tensor with a minimal set of five constants. Mean intercept length and average bone length provided an equivalent power of prediction. These results support the hypothesis that the elastic properties of human trabecular bone from an arbitrary anatomical location can be estimated from an approximation of the anisotropic morphology and a prior knowledge of tissue properties.     

A patient-specific computer tomography-based finite element methodology to calculate the six dimensional stiffness matrix of human vertebral bodies

In most finite element (FE) studies of vertebral bodies, axial compression is the loading mode of choice to investigate structural properties, but this might not adequately reflect the various loads to which the spine is subjected during daily activities or the increased fracture risk associated with shearing or bending loads. This work aims at proposing a patient-specific computer tomography (CT)-based methodology, using the currently most advanced, clinically applicable finite element approach to perform a structural investigation of the vertebral body by calculation of its full six dimensional (6D) stiffness matrix. FE models were created from voxel images after smoothing of the peripheral voxels and extrusion of a cortical shell, with material laws describing heterogeneous, anisotropic elasticity for trabecular bone, isotropic elasticity for the cortex based on experimental data. Validated against experimental axial stiffness, these models were loaded in the six canonical modes and their 6D stiffness matrix calculated. Results show that, on average, the major vertebral rigidities correlated well or excellently with the axial rigidity but that weaker correlations were observed for the minor coupling rigidities and for the image-based density measurements. This suggests that axial rigidity is representative of the overall stiffness of the vertebral body and that finite element analysis brings more insight in vertebral fragility than densitometric approaches. Finally, this extended patient-specific FE methodology provides a more complete quantification of structural properties for clinical studies at the spine.     

Computed-tomography-based finite-element models of long bones can accurately capture strain response to bending and torsion

Finite element (FE) models of long bones constructed from computed-tomography (CT) data are emerging as an invaluable tool in the field of bone biomechanics. However, the performance of such FE models is highly dependent on the accurate capture of geometry and appropriate assignment of material properties. In this study, a combined numerical-experimental study is performed comparing FE-predicted surface strains with strain-gauge measurements. Thirty-six major, cadaveric, long bones (humerus, radius, femur and tibia), which cover a wide range of bone sizes, were tested under three-point bending and torsion. The FE models were constructed from trans-axial volumetric CT scans, and the segmented bone images were corrected for partial-volume effects. The material properties (Young's modulus for cortex, density-modulus relationship for trabecular bone and Poisson's ratio) were calibrated by minimizing the error between experiments and simulations among all bones. The R(2) values of the measured strains versus load under three-point bending and torsion were 0.96-0.99 and 0.61-0.99, respectively, for all bones in our dataset. The errors of the calculated FE strains in comparison to those measured using strain gauges in the mechanical tests ranged from -6% to 7% under bending and from -37% to 19% under torsion. The observation of comparatively low errors and high correlations between the FE-predicted strains and the experimental strains, across the various types of bones and loading conditions (bending and torsion), validates our approach to bone segmentation and our choice of material properties.     

Determination of orthotropic bone elastic constants using FEA and modal analysis

Finite element models have been widely employed in an effort to quantify the stress and strain distribution around implanted prostheses and to explore the influence of these distributions on their long-term stability. In order to provide meaningful predictions, such models must contain an appropriate reflection of mechanical properties. Detailed geometrical and density information is now readily available from CT scanning. However, despite the use of phantoms, a method of determining mechanical properties (or elastic constants) from bone density has yet to be made available in a usable form.In this study, a cadaveric bone was CT scanned and its natural frequencies were measured using modal analysis. Using the geometry obtained from the CT scan data, a finite element mesh was created with the distribution of density established by matching the mass of the FE bone model with the mass of the cadaveric bone. The maximum values of the orthotropic elastic constants were then established by matching the predictions from FE modal analyses to the experimental natural frequencies, giving a maximum error of 7.8% over 4 modes of vibration. Finally, the elastic constants of the bone derived from the analyses were compared with those measured using ultrasound techniques. This produced a difference of <1% for both the maximum density and axial Young's Modulus. This study has thereby produced an orthotropic finite element model of a human femur. More importantly, however, is the implication that it is possible to create a valid FE model by simply comparing the FE results with the measured resonant frequency of the CT scanned bone.     

A patient-specific finite element methodology to predict damage accumulation in vertebral bodies under axial compression, sagittal flexion and combined loads

Due to the inherent limitations of DXA, assessment of the biomechanical properties of vertebral bodies relies increasingly on CT-based finite element (FE) models, but these often use simplistic material behaviour and/or single loading cases. In this study, we applied a novel constitutive law for bone elasticity, plasticity and damage to FE models created from coarsened pQCT images of human vertebrae, and compared vertebral stiffness, strength and damage accumulation for axial compression, anterior flexion and a combination of these two cases. FE axial stiffness and strength correlated with experiments and were linearly related to flexion properties. In all loading modes, damage localised preferentially in the trabecular compartment. Damage for the combined loading was higher than cumulated damage produced by individual compression and flexion. In conclusion, this FE method predicts stiffness and strength of vertebral bodies from CT images with clinical resolution and provides insight into damage accumulation in various loading modes.     

The impact of the parameters of the constitutive model on the distribution of strain in the femoral head

The rapid spread of the finite element method has caused that it has become, among other methods, the standard tool for pre-clinical estimates of bone properties. This paper presents an application of this method for the calculation and prediction of strain and stress fields in the femoral head. The aim of the work is to study the influence of the considered anisotropy and heterogeneity of the modeled bone on the mechanical fields during a typical gait cycle. Three material models were tested with different properties of porous bone carried out in literature: a homogeneous isotropic model, a heterogeneous isotropic model, and a heterogeneous anisotropic model. In three cases studied, the elastic properties of the bone were determined basing on the Zysset-Curnier approach. The tensor of elastic constants defining the local properties of porous bone is correlated with a local porosity and a second order fabric tensor describing the bone microstructure. In the calculations, a model of the femoral head generated from high-resolution tomographic scans was used. Experimental data were drawn from publicly available database “Osteoporotic Virtual Physiological Human Project.” To realistically reflect the load on the femoral head, main muscles were considered, and their contraction forces were determined based on inverse kinematics. For this purpose, the results from OpenSim packet were used. The simulations demonstrated that differences between the results predicted by these material models are significant. Only the anisotropic model allowed for the plausible distribution of stresses along the main trabecular groups. The outcomes also showed that the precise evaluation of the mechanical fields is critical in the context of bone tissue remodeling under mechanical stimulations.

     

Validation of a voxel-based FE method for prediction of the uniaxial apparent modulus of human trabecular bone using macroscopic mechanical tests and nanoindentation

Assessment of the mechanical properties of trabecular bone is of major biological and clinical importance for the investigation of bone diseases, fractures and their treatments. Finite element (FE) methods are getting increasingly popular for quantifying the elastic and failure properties of trabecular bone. In particular, voxel-based FE methods have been previously used to calculate the effective elastic properties of trabecular microstructures. However, in most studies, bone tissue moduli were assumed or back-calculated to match the apparent elastic moduli from experiments, which often lead to surprisingly low values when compared to nanoindentation results. In this study, voxel-based FE analysis of trabecular bone is combined with physical measures of volume fraction, micro-CT (microCT) reconstructions, uniaxial mechanical tests and specimen-specific nanoindentation tests for proper validation of the method. Cylindrical specimens of cancellous bone were extracted from human femurs and their volume fraction determined with Archimede's method. Uniaxial apparent modulus of the specimens was measured with an improved tension-compression testing protocol that minimizes boundary artefacts. Their microCT reconstructions were segmented to match the measured bone volume fraction and used to create full-size voxel models with 30-45 microm element size. For each specimen, linear isotropic elastic material properties were defined based on specific nanoindentation measurements of its embedded bone tissue. Linear FE analyses were finally performed to simulate the uniaxial mechanical tests. Additional parametric analyses were performed to evaluate the potential errors on the predicted apparent modulus arising from variations in segmentation threshold, tissue modulus, and the use of 125-mm(3) cubic sub-regions. The results demonstrate an excellent correspondence between experimental measures and FE predictions of uniaxial apparent modulus. In conclusion, the adopted voxel-based FE approach is found to be a robust method to predict the linear elastic properties of human cancellous bone, provided segmentation of the microCT reconstructions is carefully calibrated, tissue modulus is known a priori and the entire region of interest is included in the analysis.     

Orthotropic properties of cancellous bone modelled as parameterized cellular material

Analysis of stresses and strains in bone tissues and simulation of their adaptive remodelling require exhaustive information about distribution of constitutive properties of cancellous bone and their relationships to microstructural parameters. Homogenization of "equivalent" trabecular microstructures appears to be an advantageous tool for this task. In this study, parameterized orthotropic constitutive models of cancellous bone are derived from finite element analysis of repeatable microstructure cells. The models, based on a space-filling dodecahedron, are fully three-dimensional and are parameterized with four shape parameters. Variation of the parameters allows to imitate most of typical microstructure patterns observed in real bones, along with a variety of intermediate geometries. Finite element models of cells are generated by a special-purpose structured mesh generator for any arbitrary set of shape parameter values. Static numerical tests are performed for an exhaustive number of parameter value sets (microstructure instances). Coefficients of elastic orthotropic stiffness matrix are determined as tabularized functions of elastic constants versus the shape parameters. Additionally, they are correlated to apparent density and principal fabric tensor values. Comparison of the results with micro-FE data obtained for a large set of cancellous bone specimens proves a good agreement.     

Orthotropic properties of cancellous bone modelled as parameterized cellular material

Analysis of stresses and strains in bone tissues and simulation of their adaptive remodelling require exhaustive information about distribution of constitutive properties of cancellous bone and their relationships to microstructural parameters. Homogenization of “equivalent” trabecular microstructures appears to be an advantageous tool for this task. In this study, parameterized orthotropic constitutive models of cancellous bone are derived from finite element analysis of repeatable microstructure cells. The models, based on a space-filling dodecahedron, are fully three-dimensional and are parameterized with four shape parameters. Variation of the parameters allows to imitate most of typical microstructure patterns observed in real bones, along with a variety of intermediate geometries. Finite element models of cells are generated by a special-purpose structured mesh generator for any arbitrary set of shape parameter values. Static numerical tests are performed for an exhaustive number of parameter value sets (microstructure instances). Coefficients of elastic orthotropic stiffness matrix are determined as tabularized functions of elastic constants versus the shape parameters. Additionally, they are correlated to apparent density and principal fabric tensor values. Comparison of the results with micro-FE data obtained for a large set of cancellous bone specimens proves a good agreement.     

Estimation of the effective yield properties of human trabecular bone using nonlinear micro-finite element analyses

Micro-finite element (\(\upmu \)FE) analyses are often used to determine the apparent mechanical properties of trabecular bone volumes. Yet, these apparent properties depend strongly on the applied boundary conditions (BCs) for the limited size of volumes that can be obtained from human bones. To attenuate the influence of the BCs, we computed the yield properties of samples loaded via a surrounding layer of trabecular bone (“embedded configuration”). Thirteen cubic volumes (10.6 mm side length) were collected from \(\upmu \)CT reconstructions of human vertebrae and femora and converted into \(\upmu \)FE models. An isotropic elasto-plastic material model was chosen for bone tissue, and nonlinear \(\upmu \)FE analyses of six uniaxial, shear, and multi-axial load cases were simulated to determine the yield properties of a subregion (5.3 mm side length) of each volume. Three BCs were tested. Kinematic uniform BCs (KUBCs: each boundary node is constrained with uniform displacements) and periodicity-compatible mixed uniform BCs (PMUBCs: each boundary node is constrained with a uniform combination of displacements and tractions mimicking the periodic BCs for an orthotropic material) were directly applied to the subregions, while the embedded configuration was achieved by applying PMUBCs on the larger volumes instead. Yield stresses and strains, and element damage at yield were finally compared across BCs. Our findings indicate that yield strains do not depend on the BCs. However, KUBCs significantly overestimate yield stresses obtained in the embedded configuration (+43.1 ± 27.9%). PMUBCs underestimate (?10.0 ± 11.2%), but not significantly, yield stresses in the embedded situation. Similarly, KUBCs lead to higher damage levels than PMUBCs (+51.0 ± 16.9%) and embedded configurations (+48.4 ± 15.0%). PMUBCs are better suited for reproducing the loading conditions in subregions of the trabecular bone and deliver a fair estimation of their effective (asymptotic) yield properties.