Performance of QCT-Derived scapula finite element models in predicting local displacements using digital volume correlation

Subject-specific finite element models (FEMs) of the shoulder complex are commonly used to predict differences in internal load distribution due to injury, treatment or disease. However, these models rely on various underlying assumptions, and although experimental validation is warranted, it is difficult to obtain and often not performed. The goal of the current study was to quantify the accuracy of local displacements predicted by subject-specific QCT-based FEMs of the scapula, compared to experimental measurements obtained by combining digital volume correlation (DVC) and mechanical loading of cadaveric specimens within a microCT scanner. Four cadaveric specimens were loaded within a microCT scanner using a custom-designed six degree-of-freedom hexapod robot augmented with carbon fiber struts for radiolucency. BoneDVC software was used to quantify full-field experimental displacements between pre- and post-loaded scans. Corresponding scapula QCT-FEMs were generated and three types of boundary conditions (BC) (idealized-displacement, idealized-force, and DVC-derived) were simulated for each specimen. DVC-derived BCs resulted in the closest match to the experimental results for all specimens (best agreement: slope ranging from 0.87 to 1.09; highest correlation: r2 ranging from 0.79 to 1.00). In addition, a two orders of magnitude decrease was observed in root-mean-square error when using QCT-FEMs with simulated DVC-derived BCs compared to idealized-displacement and idealized-force BCs. The results of this study demonstrate that scapula QCT-FEMs can accurately predict local experimental full-field displacements if the BCs are derived from DVC measurements

Precision of Digital Volume Correlation Approaches for Strain Analysis in Bone Imaged with Micro-Computed Tomography at Different Dimensional Levels

Accurate measurement of local strain in heterogeneous and anisotropic bone tissue is fundamental to understand the pathophysiology of musculoskeletal diseases, to evaluate the effect of interventions from preclinical studies, and to optimize the design and delivery of biomaterials. Digital volume correlation (DVC) can be used to measure the three-dimensional displacement and strain fields from micro-computed tomography (μCT) images of loaded specimens. However, this approach is affected by the quality of the input images, by the morphology and density of the tissue under investigation, by the correlation scheme, and by the operational parameters used in the computation. Therefore, for each application, the precision of the method should be evaluated. In this paper, we present the results collected from datasets analyzed in previous studies as well as new data from a recent experimental campaign for characterizing the relationship between the precision of two different DVC approaches and the spatial resolution of the outputs. Different bone structures scanned with laboratory source μCT or synchrotron light μCT (SRμCT) were processed in zero-strain tests to evaluate the precision of the DVC methods as a function of the subvolume size that ranged from 8 to 2,500 µm. The results confirmed that for every microstructure the precision of DVC improves for larger subvolume size, following power laws. However, for the first time, large differences in the precision of both local and global DVC approaches have been highlighted when SRμCT or in vivo μCT images were used instead of conventional ex vivo μCT. These findings suggest that in situ mechanical testing protocols applied in SRμCT facilities should be optimized to allow DVC analyses of localized strain measurements. Moreover, for in vivo μCT applications, DVC analyses should be performed only with relatively course spatial resolution for achieving a reasonable precision of the method. In conclusion, we have extensively shown that the precision of both tested DVC approaches is affected by different bone structures, different input image resolution, and different subvolume sizes. Before each specific application, DVC users should always apply a similar approach to find the best compromise between precision and spatial resolution of the measurements

Material mapping of QCT-derived scapular models : a comparison with micro-CT loaded specimens using digital volume correlation

Subject- and site-specific modeling techniques greatly improve finite element models (FEMs) derived from clinical-resolution CT data. A variety of density-modulus relationships are used in scapula FEMs, but the sensitivity to selection of relationships has yet to be experimentally evaluated. The objectives of this study were to compare quantitative-CT (QCT) derived FEMs mapped with different density-modulus relationships and material mapping strategies to experimentally loaded cadaveric scapular specimens. Six specimens were loaded within a micro-CT (33.5 μm isotropic voxels) using a custom-hexapod loading device. Digital volume correlation (DVC) was used to estimate full-field displacements by registering images in pre- and post-loaded states. Experimental loads were measured using a 6-DOF load cell. QCT-FEMs replicated the experimental setup using DVC-driven boundary conditions (BCs) and were mapped with one of fifteen density-modulus relationships using elemental or nodal material mapping strategies. Models were compared based on predicted QCT-FEM nodal reaction forces compared to experimental load cell measurements and linear regression of the full-field nodal displacements compared to the DVC full-field displacements. Comparing full-field displacements, linear regression showed slopes ranging from 0.86 to 1.06, r-squared values of 0.82–1.00, and max errors of 0.039 mm for all three Cartesian directions. Nearly identical linear regression results occurred for both elemental and nodal material mapping strategies. Comparing QCT-FEM to experimental reaction forces, errors ranged from − 46 to 965% for all specimens, with specimen-specific errors as low as 3%. This study utilized volumetric imaging combined with mechanical loading to derive full-field experimental measurements to evaluate various density-modulus relationships required for QCT-FEMs applied to whole-bone scapular loading. The results suggest that elemental and nodal material mapping strategies are both able to simultaneously replicate experimental full-field displacements and reactions forces dependent on the density-modulus relationship used

MicroFE models of porcine vertebrae with induced bone focal lesions : validation of predicted displacements with digital volume correlation

The evaluation of the local mechanical behavior as a result of metastatic lesions is fundamental for the characterization of the mechanical competence of metastatic vertebrae. Micro finite element (microFE) models have the potential of addressing this challenge through laboratory studies but their predictions of local deformation due to the complexity of the bone structure compromized by the lesion must be validated against experiments. In this study, the displacements predicted by homogeneous, linear and isotropic microFE models of vertebrae were validated against experimental Digital Volume Correlation (DVC) measurements. Porcine spine segments, with and without mechanically induced focal lesions, were tested in compression within a micro computed tomography (microCT) scanner. The displacement within the bone were measured with an optimized global DVC approach (BoneDVC). MicroFE models of the intact and lesioned vertebrae, including or excluding the growth plates, were developed from the microCT images. The microFE and DVC boundary conditions were matched. The displacements measured by the DVC and predicted by the microFE along each Cartesian direction were compared. The results showed an excellent agreement between the measured and predicted displacements, both for intact and metastatic vertebrae, in the middle of the vertebra, in those cases where the structure was not loaded beyond yield (0.69 < R2 < 1.00). Models with growth plates showed the worst correlations (0.02 < R2 < 0.99), while a clear improvement was observed if the growth plates were excluded (0.56 < R2 < 1.00). In conclusion, these simplified models can predict complex displacement fields in the elastic regime with high reliability, more complex non-linear models should be implemented to predict regions with high deformation, when the bone is loaded beyond yield

A novel approach to evaluate the effects of artificial bone focal lesion on the three-dimensional strain distributions within the vertebral body

The spine is the first site for incidence of bone metastasis. Thus, the vertebrae have a high potential risk of being weakened by metastatic tissues. The evaluation of strength of the bone affected by the presence of metastases is fundamental to assess the fracture risk. This work proposes a robust method to evaluate the variations of strain distributions due to artificial lesions within the vertebral body, based on in situ mechanical testing and digital volume correlation. Five porcine vertebrae were tested in compression up to 6500N inside a micro computed tomography scanner. For each specimen, images were acquired before and after the application of the load, before and after the introduction of the artificial lesions. Principal strains were computed within the bone by means of digital volume correlation (DVC). All intact specimens showed a consistent strain distribution, with peak minimum principal strain in the range -1.8% to -0.7% in the middle of the vertebra, demonstrating the robustness of the method. Similar distributions of strains were found for the intact vertebrae in the different regions. The artificial lesion generally doubled the strain in the middle portion of the specimen, probably due to stress concentrations close to the defect. In conclusion, a robust method to evaluate the redistribution of the strain due to artificial lesions within the vertebral body was developed and will be used in the future to improve current clinical assessment of fracture risk in metastatic spines

PTH(1–34) treatment and/or mechanical loading have different osteogenic effects on the trabecular and cortical bone in the ovariectomized C57BL/6 mouse

In preclinical mouse models, a synergistic anabolic response to PTH(1–34) and tibia loading was shown. Whether combined treatment improves bone properties with oestrogen deficiency, a cardinal feature of osteoporosis, remains unknown. This study quantified the individual and combined longitudinal effects of PTH(1–34) and loading on the bone morphometric and densitometric properties in ovariectomised mice. C57BL/6 mice were ovariectomised at 14-weeks-old and treated either with injections of PTH(1–34); compressive loading of the right tibia; both interventions concurrently; or both interventions on alternating weeks. Right tibiae were microCT-scanned from 14 until 24-weeks-old. Trabecular metaphyseal and cortical midshaft morphometric properties, and bone mineral content (BMC) in 40 different regions of the tibia were measured. Mice treated only with loading showed the highest trabecular bone volume fraction at week 22. Cortical thickness was higher with co-treatment than in the mice treated with PTH alone. In the mid-diaphysis, increases in BMC were significantly higher with loading than PTH. In ovariectomised mice, the osteogenic benefits of co-treatment on the trabecular bone were lower than loading alone. However, combined interventions had increased, albeit regionally-dependent, benefits to cortical bone. Increased benefits were largest in the mid-diaphysis and postero-laterally, regions subjected to higher strains under compressive loads

A new method to monitor bone geometry changes at different spatial scales in the longitudinal in vivo μCT studies of mice bones

Longitudinal studies of bone adaptation in mice using in vivo micro-computed tomography (μCT) have been commonly used for pre-clinical evaluation of physical and pharmacological interventions. The main advantage of this approach is to use each mouse as its own control, reducing considerably the sample size required by statistical power analysis. To date, multi-scale estimation of bone adaptations become essential since the bone activity that takes place at different scales may be associated with different bone mechanisms. Measures of bone adaptations at different time scales have been attempted in a previous study. This paper extends quantification of bone activity at different spatial scales with a proposition of a novel framework. The method involves applying level-set method (LSM) to track the geometric changes from the longitudinal in vivo μCT scans of mice tibia. Bone low- and high-spatial frequency patterns are then estimated using multi-resolution analysis. The accuracy of the framework is quantified by applying it to two times separated scanned images with synthetically manipulated global and/or local activity. The Root Mean Square Deviation (RMSD) was approximately 1.5 voxels or 0.7 voxels for the global low-spatial frequency or local high-spatial frequency changes, respectively. The framework is further applied to the study of bone changes in longitudinal datasets of wild-type mice tibiae over time and space. The results demonstrate the ability for the spatio-temporal quantification and visualisation of bone activity at different spatial scales in longitudinal studies thus providing further insight into bone adaptation mechanisms

Bone metastases do not affect the measurement uncertainties of a global digital volume correlation algorithm

Introduction: Measurement uncertainties of Digital Volume Correlation (DVC) are influenced by several factors, like input images quality, correlation algorithm, bone type, etc. However, it is still unknown if highly heterogeneous trabecular microstructures, typical of lytic and blastic metastases, affect the precision of DVC measurements. Methods: Fifteen metastatic and nine healthy vertebral bodies were scanned twice in zero-strain conditions with a micro-computed tomography (isotropic voxel size = 39 μm). The bone microstructural parameters (Bone Volume Fraction, Structure Thickness, Structure Separation, Structure Number) were calculated. Displacements and strains were evaluated through a global DVC approach (BoneDVC). The relationship between the standard deviation of the error (SDER) and the microstructural parameters was investigated in the entire vertebrae. To evaluate to what extent the measurement uncertainty is influenced by the microstructure, similar relationships were assessed within sub-regions of interest. Results: Higher variability in the SDER was found for metastatic vertebrae compared to the healthy ones (range 91-1030 με versus 222–599 με). A weak correlation was found between the SDER and the Structure Separation in metastatic vertebrae and in the sub-regions of interest, highlighting that the heterogenous trabecular microstructure only weakly affects the measurement uncertainties of BoneDVC. No correlation was found for the other microstructural parameters. The spatial distribution of the strain measurement uncertainties seemed to be associated with regions with reduced greyscale gradient variation in the microCT images. Discussion: Measurement uncertainties cannot be taken for granted but need to be assessed in each single application of the DVC to consider the minimum unavoidable measurement uncertainty when interpreting the results

A new method to monitor bone geometry changes at different spatial scales in the longitudinal in vivo μCT studies of mice bones

Longitudinal studies of bone adaptation in mice using in vivo micro-computed tomography (μCT) have been commonly used for pre-clinical evaluation of physical and pharmacological interventions. The main advantage of this approach is to use each mouse as its own control, reducing considerably the sample size required by statistical power analysis. To date, multi-scale estimation of bone adaptations become essential since the bone activity that takes place at different scales may be associated with different bone mechanisms. Measures of bone adaptations at different time scales have been attempted in a previous study. This paper extends quantification of bone activity at different spatial scales with a proposition of a novel framework. The method involves applying level-set method (LSM) to track the geometric changes from the longitudinal in vivo μCT scans of mice tibia. Bone low- and high-spatial frequency patterns are then estimated using multi-resolution analysis. The accuracy of the framework is quantified by applying it to two times separated scanned images with synthetically manipulated global and/or local activity. The Root Mean Square Deviation (RMSD) was approximately 1.5 voxels or 0.7 voxels for the global low-spatial frequency or local high-spatial frequency changes, respectively. The framework is further applied to the study of bone changes in longitudinal datasets of wild-type mice tibiae over time and space. The results demonstrate the ability for the spatio-temporal quantification and visualisation of bone activity at different spatial scales in longitudinal studies thus providing further insight into bone adaptation mechanisms

Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

BACKGROUND: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have never been investigated. METHODS: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases, and older controls not affected by neurological diseases but scheduled for venography (HAV-C), blindly underwent a combined transcranial and extracranial Color-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. RESULTS: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29-65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; it configures a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated to CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher. CONCLUSION: CDMS is strongly associated with CCSVI, a picture never been described so far, characterized by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease