2D-3D reconstruction of the proximal femur from DXA scans: Evaluation of the 3D-Shaper software.

Introduction: Osteoporosis is currently diagnosed based on areal bone mineral density (aBMD) computed from 2D DXA scans. However, aBMD is a limited surrogate for femoral strength since it does not account for 3D bone geometry and density distribution. QCT scans combined with finite element (FE) analysis can deliver improved femoral strength predictions. However, non-negligible radiation dose and high costs prevent a systematic usage of this technique for screening purposes. As an alternative, the 3D-Shaper software (3D-Shaper Medical, Spain) reconstructs the 3D shape and density distribution of the femur from 2D DXA scans. This approach could deliver a more accurate estimation of femoral strength than aBMD by using FE analysis on the reconstructed 3D DXA. Methods: Here we present the first independent evaluation of the software, using a dataset of 77 ex vivo femora. We extend a prior evaluation by including the density distribution differences, the spatial correlation of density values and an FE analysis. Yet, cortical thickness is left out of this evaluation, since the cortex is not resolved in our FE models. Results: We found an average surface distance of 1.16 mm between 3D DXA and QCT images, which shows a good reconstruction of the bone geometry. Although BMD values obtained from 3D DXA and QCT correlated well (r 2 = 0.92), the 3D DXA BMD were systematically lower. The average BMD difference amounted to 64 mg/cm3, more than one-third of the 3D DXA BMD. Furthermore, the low correlation (r 2 = 0.48) between density values of both images indicates a limited reconstruction of the 3D density distribution. FE results were in good agreement between QCT and 3D DXA images, with a high coefficient of determination (r 2 = 0.88). However, this correlation was not statistically different from a direct prediction by aBMD. Moreover, we found differences in the fracture patterns between the two image types. QCT-based FE analysis resulted mostly in femoral neck fractures and 3D DXA-based FE in subcapital or pertrochanteric fractures. Discussion: In conclusion, 3D-Shaper generates an altered BMD distribution compared to QCT but, after careful density calibration, shows an interesting potential for deriving a standardized femoral strength from a DXA scan

Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments

Computed tomography (CT)-based finite element (FE) models may improve the current osteoporosis diagnostics and prediction of fracture risk by providing an estimate for femoral strength. However, the need for a CT scan, as opposed to the conventional use of dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnostics, is considered a major obstacle. The 3D shape and bone mineral density (BMD) distribution of a femur can be reconstructed using a statistical shape and appearance model (SSAM) and the DXA image of the femur. Then, the reconstructed shape and BMD could be used to build FE models to predict bone strength. Since high accuracy is needed in all steps of the analysis, this study aimed at evaluating the ability of a 3D FE model built from one 2D DXA image to predict the strains and fracture load of human femora. Three cadaver femora were retrieved, for which experimental measurements from ex vivo mechanical tests were available. FE models were built using the SSAM-based reconstructions: using only the SSAM-reconstructed shape, only the SSAM-reconstructed BMD distribution, and the full SSAM-based reconstruction (including both shape and BMD distribution). When compared with experimental data, the SSAM-based models predicted accurately principal strains (coefficient of determination >0.83, normalized root-mean-square error <16%) and femoral strength (standard error of the estimate 1215 N). These results were only slightly inferior to those obtained with CT-based FE models, but with the considerable advantage of the models being built from DXA images. In summary, the results support the feasibility of SSAM-based models as a practical tool to introduce FE-based bone strength estimation in the current fracture risk diagnostics

Generation of 3D shape, density, cortical thickness and finite element mesh of proximal femur from a DXA image

Areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), predicts hip fracture risk only moderately. Simulation of bone mechanics based on DXA imaging of the proximal femur, may help to improve the prediction accuracy. Therefore, we collected three (1-3) image sets, including CT images and DXA images of 34 proximal cadaver femurs (set1, including 30 males, 4 females), 35 clinical patient CT images of the hip (set 2, including 27 males, 8 females) and both CT and DXA images of clinical patients (set 3, including 12 female patients). All CT images were segmented manually and landmarks were placed on both femurs and pelvises. Two separate statistical appearance models (SAMs) were built using the CT images of the femurs and pelvises in sets 1 and 2, respectively. The 3D shape of the femur was reconstructed from the DXA image by matching the SAMs with the DXA images. The orientation and modes of variation of the SAMs were adjusted to minimize the sum of the absolute differences between the projection of the SAMs and a DXA image. The mesh quality and the location of the SAMs with respect to the manually placed control points on the DXA image were used as additional constraints. Then, finite element (FE) models were built from the reconstructed shapes. Mean point-to-surface distance between the reconstructed shape and CT image was 1.0mm for cadaver femurs in set 1 (leave-one-out test) and 1.4mm for clinical subjects in set 3. The reconstructed volumetric BMD showed a mean absolute difference of 140 and 185mg/cm3 for set 1 and set 3 respectively. The generation of the SAM and the limitation of using only one 2D image were found to be the most significant sources of errors in the shape reconstruction. The noise in the DXA images had only small effect on the accuracy of the shape reconstruction. DXA-based FE simulation was able to explain 85% of the CT-predicted strength of the femur in stance loading. The present method can be used to accurately reconstruct the 3D shape and internal density of the femur from 2D DXA images. This may help to derive new information from clinical DXA images by producing patient-specific FE models for mechanical simulation of femoral bone mechanics

A shape analysis approach to prediction of bone stiffness using FEXI

The preferred method of assessing the risk of an osteoporosis related fracture is currently a measure of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). However, other factors contribute to the overall risk of fracture, including anatomical geometry and the spatial distribution of bone. Finite element analysis can be performed in both two and three dimensions, and predicts the deformation or induced stress when a load is applied to a structure (such as a bone) of defined material composition and shape. The simulation of a mechanical compression test provides a measure of whole bone stiffness (N mm−1). A simulation system was developed to study the sensitivity of BMD, 3D and 2D finite element analysis to variations in geometric parameters of a virtual proximal femur model. This study demonstrated that 3D FE and 2D FE (FEXI) were significantly more sensitive to the anatomical shape and composition of the proximal femur than conventional BMD. The simulation approach helped to analyse and understand how variations in geometric parameters affect the stiffness and hence strength of a bone susceptible to osteoporotic fracture. Originally, the FEXI technique modelled the femur as a thin plate model of an assumed constant depth for finite element analysis (FEA). A better prediction of tissue depth across the bone, based on its geometry, was required to provide a more accurate model for FEA. A shape template was developed for the proximal femur to provide this information for the 3D FE analysis. Geometric morphometric techniques were used to procure and analyse shape information from a set of CT scans of excised human femora. Generalized Procrustes Analysis and Thin Plate Splines were employed to analyse the data and generate a shape template for the proximal femur. 2D Offset and Depth maps generated from the training set data were then combined to model the three-dimensional shape of the bone. The template was used to predict the three-dimensional bone shape from a 2D image of the proximal femur procured through a DXA scan. The error in the predicted 3D shape was measured as the difference in predicted and actual depths at each pixel. The mean error in predicted depths was found to be 1.7mm compared to an average bone depth of 34mm. 3D FEXI analysis on the predicted 3D bone along with 2D FEXI for a stance loading condition and BMD measurement were performed based on 2D radiographic projections of the CT scans and compared to bone stiffness results obtained from finite element analysis of the original 3D CT scans. 3D FEXI provided a significantly higher correlation (R2 = 0.85) with conventional CT derived 3D finite element analysis than achieved with both BMD (R2 = 0.52) and 2D FEXI (R2 = 0.44)

Femoral Strength Prediction using Finite Element Models : Validation of models based on CT and reconstructed DXA images against full-field strain measurements

Osteoporosis is defined as low bone density, and results in a markedly increased risk of skeletal fractures. It has been estimated that about 40% of all women above 50 years old will suffer from an osteoporotic fracture leading to hospitalization. Current osteoporosis diagnostics is largely based on statistical tools, using epidemiological parameters and bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA). However, DXA-based BMD proved to be only a moderate predictor of bone strength. Therefore, novel methods that take into account all mechanical characteristics of the bone and their influence on bone resistance to fracture are advocated. Finite element (FE) models may improve the bone strength prediction accuracy, since they can account for the structural determinants of bone strength, and the variety of external loads acting on the bones during daily life. Several studies have proved that FE models can perform better than BMD as a bone strength predictor. However, these FE models are built from Computed Tomography (CT) datasets, as the 3D bone geometry is required, and take several hours of work by an experienced engineer. Moreover, the radiation dose for the patient is higher for CT than for DXA scan. All these factors contributed to the low impact that FE-based methods have had on the current clinical practice so far. This thesis work aimed at developing accurate and thoroughly validated FE models to enable a more accurate prediction of femoral strength. An accurate estimation of femoral strength could be used as one of the main determinant of a patient’s fracture risk during population screening. In the first part of the thesis, the ex vivo mechanical tests performed on cadaver human femurs are presented. Digital image correlation (DIC), an optical method that allows for a full-field measurement of the displacements over the femur surface, was used to retrieve strains during the test. Then, a subject-specific FE modelling technique able to predict the deformation state and the overall strength of human femurs is presented. The FE models were based on clinical images from 3D CT datasets, and were validated against the measurements collected during the ex vivo mechanical tests. Both the experimental setup with DIC and the FE modelling procedure have been initially tested using composite bones (only the FE part of the composite bone study is presented in this thesis). After that, the method was extended to human cadaver bones. Once validated against experimental strain measurements, the FE modelling procedure could be used to predict bone strength. In the last part of the thesis, the predictive ability of FE models based on the shape and BMD distribution reconstructed from a single DXA image using a statistical shape and appearance model (SSAM, developed outside this thesis) was assessed. The predictions were compared to the experimental measurements, and the obtained accuracy compared to that of CT-based FE models. The results obtained were encouraging. The CT-based FE models were able to predict the deformation state with very good accuracy when compared to thousands of full-field measurements from DIC (normalized root mean square error, NRMSE, below 11%), and, most importantly, could predict the femoral strength with an error below 2%. The performances of SSAM-based FE models were also promising, showing only a slight reduction of the performances when compared to the CT-based approach (NRMSE below 20% for the strain prediction, average strength prediction error of 12%), but with the significant advantage of the models being built from one single conventional DXA image. In conclusion, the concept of a new, accurate and semi-automatic FE modelling procedure aimed at predicting fracture risk on individuals was developed. The performances of CT-based and SSAM-based models were thoroughly compared, and the results support the future translation of SSAM-based FE model built from a single DXA image into the clinics. The developed tool could therefore allow to include a mechanistic information into the fracture risk screening, which may ultimately lead to an increased accuracy in the identification of the subjects at risk

Generation of a statistical model of the anatomy of human pelvises

Osteoarthritis and osteoporosis are two medical conditions involving the hip which affect the life quality of many people worldwide. These two diseases are diagnosed with 2D imaging by analysis of radiological measures, bone mineral density and joint space. Computed Tomography (CT) can provide 3D images of the hip, but has higher cost and imposes a higher radiation dose to the patient. Another option (which the Biomechanics group in Lund is working on) is to utilize statistical models to construct a 3D model from a 2D image. The Biomechanics group has developed a statistical model of the anatomical variability of the human femur. Adding an equivalent model for the pelvis would then allow to fully represent the hip joint. In this study, CT scans from 26 male and 21 female patients scheduled for hip replacement surgery were used to create a Statistical Shape Model (SSM) to describe the shape of pelvis. To be able to generate the SSM, the shapes of all bones were defined by identical meshes. A template mesh was created based on one of the available anatomies and it was then registered to each hip bone. The registered bones were then used to create the SSM. The registration method was evaluated by a point-to-surface distance difference. For the SSM, the shape variation and the reconstruction of the hip bones were evaluated for the whole group and for the male and female patient cohorts within the group. The SSM created during the study was able to represent the shape variation of both male and female bones. Visually, the gender variance was associated to the width and thickness of the bone, corresponding with the known differences of the pelvic bone between the genders. The results indicate that the model can represent the shape of the bone accurately, independent of gender. Combined with a statistical model for the femur, the SSM created in this study can be used to provide a 2D to 3D reconstruction of the hip from clinical diagnostic images.3D-modell av höftbenet kan hjälpa till att förutspå artros Det är viktigt att förebygga sjukdomar innan de bryter ut. Vanliga 2D-röntgenbilder är inte alltid tillräckligt noggranna men med 3D-modeller kan tidiga tecken på artros lättare identifieras. Vi strävar för att få fram 3D-bilder av höften från vanliga röntgenbilder

Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected

Analysis of Bone Architecture in Rodents Using Micro-Computed Tomography.

This chapter describes the use of micro-computed tomography scanning for analyzing bone structure, focussing on rodent bone. It discusses sample preparation, the correct setup of the scanner, the impact of some of the important scanner settings and new applications