Anisotropy of dynamic acoustoelasticity in limestone, influence of conditioning, and comparison with nonlinear resonance spectroscopy.

Anisotropy of wave velocity and attenuation induced by a dynamic uniaxial strain is investigated by dynamic acoustoelastic testing in limestone. Nonlinear resonance spectroscopy is performed simultaneously for comparison. A compressional resonance of the sample at 6.8 kHz is excited to produce a dynamic strain with an amplitude varied from 10(-7) to 10(-5). A sequence of ultrasound pulses tracks variations in ultrasonic velocity and attenuation. Variations measured when the ultrasound pulses propagate in the direction of the uniaxial strain are 10 times larger than when the ultrasound propagation occurs perpendicularly. Variations consist of a "fast" variation at 6.8 kHz and an offset. Acoustically induced conditioning is found to reduce wave velocity and enhance attenuation (offset). It also modifies "fast" nonlinear elastodynamics, i.e., wave amplitude dependencies of ultrasonic velocity and attenuation. At the onset of conditioning and beyond, different excitation amplitudes bring the material to non-equilibrium states. After conversion of velocity-strain dynamic relations into elastic modulus-strain dynamic relations and integration with respect to strain, the dynamic stress-strain relation is obtained. Analysis of stress-strain hysteresis shows that hysteretic nonlinear elasticity is not a significant source of the amplitude-dependent dissipation measured by nonlinear resonance spectroscopy. Mechanisms causing conditioning are likely producing amplitude-dependent dissipation as well.

Nonlinear elastodynamics in micro-inhomogeneous solids observed by head-wave based dynamic acoustoelastic testing.

Dynamic acoustoelastic testing provides a more complete insight into the acoustic nonlinearity exhibited by micro-inhomogeneous media like granular and cracked materials. This method consists of measuring time of flight and energy modulations of pulsed ultrasonic waves induced by a low-frequency standing wave. Here pulsed ultrasonic head waves were employed to assess elastic and dissipative nonlinearities in a region near the surface of a solid. Synchronization of the ultrasound pulse sequence with the low-frequency excitation provided instantaneous variations in the elastic modulus and the attenuation as functions of the instantaneous low-frequency strain. Weak quadratic elastic nonlinearity and no dissipative nonlinearity were detected in duralumin. In limestone, distinction between tensile and compressive behaviors revealed an asymmetry in the acoustic nonlinearity and hysteresis in both the elastic modulus and the attenuation variations. Measured nonlinear acoustical parameters are in good agreement with values obtained by different techniques. Reversible acoustically induced conditioning modified the acoustic nonlinearity both quantitatively and qualitatively. It reduced tension-compression asymmetry, suggesting a nonequilibrium modification of the sources of acoustic nonlinearity. Additionally to the metrology of the acoustic nonlinearity, head wave based dynamic acoustoelastic testing may be a useful tool to monitor changes in the microstructure or the accumulation of damage in solids.

Femur ultrasound (FemUS)--first clinical results on hip fracture discrimination and estimation of femoral BMD.

SUMMARY: A quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis. INTRODUCTION: Dual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance. METHODS: Using the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed. RESULTS: Hip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R (2) up to 0.72 and a residual error of about one half of a T-score in BMD. CONCLUSIONS: QUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study.

Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = -0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.

Relationships of trabecular bone structure with quantitative ultrasound parameters: in vitro study on human proximal femur using transmission and backscatter measurements.

The present study was designed to assess the relationships between QUS parameters and bone density or microarchitecture on samples of human femoral trabecular bone. The normalized slope of the frequency-dependent attenuation (nBUA), the speed of sound (SOS) and the broadband ultrasound backscatter coefficient (BUB) were measured on 37 specimens of pure trabecular bones removed from upper parts of fresh human femurs. Bone mineral density (BMD) was assessed using a clinical scanner. Finally, 8 mm diameter cylindrical cores were extracted from the specimens and their microarchitecture was reconstructed after synchrotron radiation microtomography experiments (isotropic resolution of 10 microm). A large number of microarchitectural parameters were computed, describing morphology, connectivity and geometry of the specimens. BMD correlated with all the microarchitectural parameters and the number of significant correlations was found among the architectural parameters themselves. All QUS parameters were significantly correlated to BMD (R=0.83 for nBUA, R=0.81 for SOS and R=0.69 for BUB) and to microarchitectural parameters (R=-0.79 between nBUA and Tb.Sp, R=-0.81 between SOS and Tb.Sp, R=-0.65 between BUB and BS/BV). Using multivariate model, it was found that microstructural parameters adds 10%, 19%, and 4% to the respective BMD alone contribution for the three variables BUA, SOS and BUB. Moreover, the RMSE was reduced by up to 50% for SOS, by up to 21% for nBUA and up to 11% when adding structural variables to BMD in explaining QUS results. Given the sample, which is not osteoporosis-enriched, the added contribution is quite substantial. The variability of SOS was indeed completely explained by a multivariate model including BMD and independent structural parameters (R(2)=0.94). The inverse problem on the data presented here has been addressed using simple and multiple linear regressions. It was shown that the predictions (in terms of R(2) or RMSE) of microarchitectural parameters was not enhanced when combining 2 or 3 QUS in multiple linear regressions compared to the prediction obtained with one QUS parameter alone. The best model was found for the prediction of Tb.Th() from BUA (R(2)=0.58, RMSE=17 microm). Given the high values of RMSE, these linear models appear of limited clinical value, suggesting that appropriate models have to be derived in order to solve the inverse problem. In this regard, a very interesting multivariate model was found for nBUA and BUB with Tb.Th and Tb.N, in agreement with single scattering theories by random medium. However, the source of residual variability of nBUA and BUB (15% and 45% respectively) remained unexplained.

Spatial distribution of anisotropic acoustic impedance assessed by time-resolved 50-MHz scanning acoustic microscopy and its relation to porosity in human cortical bone.

We used quantitative scanning acoustic microscopy (SAM) to assess tissue acoustic impedance and microstructure of cortical bone of human radii with the aim to provide data on regional distribution of acoustic impedance along the circumferential and across the radial directions in the entire cross-section of the radius diaphysis as well as to determine the range of impedance values in transverse (perpendicular to bone axis) and longitudinal (parallel to bone axis) cross-sections. Several microstructural features related to cortical porosity were analyzed in order to determine whether these features differ in different parts of the cortex and to assess the relationship between the microstructure and tissue acoustic impedance. Fifteen fresh bone specimens (human radius) were investigated using a SAM (center frequency of 50 MHz and -6 dB lateral resolution of approximately 23 microm). The sample acoustic impedance was obtained by means of a calibration curve correlating the reflected signal amplitude of reference materials with their corresponding well-known acoustic impedance. Tissue acoustic impedance and microstructural features were derived from the morphometric analysis of the segmented impedance images. A higher porosity was found in the inner cortical layer (mean+/-SD=8.9+/-2.3%) compared to the peripheral layer (2.7+/-1.5%) (paired t-test, p<10(-5)). ANOVA showed that most of the variance can be explained by the regional effect across the radial direction with a minor contribution due to between-sample variability. Similar to porosity, the number and diameter of pores were greater in the inner layer. In contrast to porosity, ANOVA showed that impedance variability can mostly be explained by between-specimen variability. Two-way ANOVA revealed that after compensation for the between-sample variability the variation in acoustic impedance across the radial direction was much larger than that along the circumferential direction. In addition to the significant difference between the inner cortical layer (8.25+/-0.4 Mrayl) and peripheral layer (8.0+/-0.5 Mrayl) (unilateral paired t-test, p<10(-4)), the values in the anterior region (8.2+/-0.5 Mrayl) were found to be significantly higher than those of the posterior region (7.9+/-0.6 Mrayl). Impedance mean value of longitudinal sections was lower than mean value measured in transverse cross-sections, resulting in an impedance acoustic anisotropy ratio of 1.17+/-0.03 in the inner cortical layer and 1.19+/-0.02 in the peripheral layer. SAM is a valuable tool to provide data on the spatial distribution of microstructural and microelastic bone properties that is useful to improve our understanding of the impact of bone microstructure on tissue material properties.

Nonlinear ultrasound can detect accumulated damage in human bone.

Bone micro-damage is commonly accepted as a relevant parameter for fracture risk assessment, but there is no available technique for its non-invasive characterization. The objective of this work is to study the potential of nonlinear ultrasound for damage detection in human bone. Ultrasound is particularly desirable due to its non-invasive and non-ionizing characteristics. We show results illustrating the correlation of progressive fatigue of human bone samples to their nonlinear dynamical response. In our experiments, damage was induced in 30 samples of diaphyseal human femur using fatigue cycling. At intervals in the cycling, the nonlinear response of the samples was assessed applying Nonlinear Resonant Ultrasound Spectroscopy (NRUS). The nonlinear parameter alpha, which in other materials correlates with the quantity of damage, dramatically increased with the number of mechanical testing cycles. We find a large spread in alpha in the pristine samples and infer that the spread is due to damage differences in the sample population. As damage accumulates during cycling, we find that alpha is much more sensitive to damage than other quantities measured, including the slope and hysteresis of the load/displacement curve, and the dynamic wavespeed. To our knowledge, this study represents the first application of the concept of nonlinear dynamic elasticity to human bone. The results are promising, suggesting the value of further work on this topic. Ultimately, the approach may have merit for in vivo bone damage characterization.

Prediction of bone mechanical properties using QUS and pQCT: study of the human distal radius.

The objective was to compare the prediction of bone mechanical properties provided by axial transmission to that provided by peripheral quantitative computed tomography (pQCT) at the distal radius. The distal radius is the location for Colles' fractures, a common osteoporosis related trauma situation. Measurements of the radial speed of sound were performed using three axial transmission devices: a commercial device (Sunlight Omnisense, 1.25 MHz), a bi-directional axial transmission prototype (1 MHz), both measuring the velocity of the first arriving signal (FAS), and a low frequency (200 kHz) device, measuring the velocity of a slower wave. Co-localized pQCT measurements of bone mineral density and cortical thickness were performed. Ultrasound and pQCT parameters were compared to mechanical parameters such as failure load and Young's modulus, obtained using quasistatic compressive mechanical testing and finite elements modelling (FEM). Correlations of the ultrasound and pQCT parameters to mechanical parameters were comparable. The best predictor of failure load was the pQCT measured cortical thickness. The best predictor of Young's modulus was the bi-directional SOS. The low frequency device significantly correlated to cortical thickness and failure load. The results suggest that different axial transmission approaches give access to different bone mechanical parameters. The association of different axial transmission techniques should be able to provide a good prediction of bone mechanical parameters, and should therefore be helpful for fracture risk prediction.

Fast wave ultrasonic propagation in trabecular bone: numerical study of the influence of porosity and structural anisotropy.

Our goal is to assess the potential of computational methods as an alternative to analytical models to predict the two longitudinal wave modes observed in cancellous bone and predicted by the Biot theory. A three-dimensional (3D) finite-difference time-domain method is coupled with 34 human femoral trabecular microstructures measured using microcomputed tomography. The main trabecular alignment (MTA) and the degree of anisotropy (DA) were assessed for all samples. DA values were comprised between 1.02 and 1.9. The influence of bone volume fraction (BV/TV) between 5% and 25% on the properties of the fast and slow waves was studied using a dedicated image processing algorithm to modify the initial 3D microstructures. A heuristic method was devised to determine when both wave modes are time separated. The simulations (performed in three perpendicular directions) predicted that both waves generally overlap in time for a direction of propagation perpendicular to the MTA. When these directions are parallel, both waves are separated in time for samples with high DA and BV/TV values. A relationship was found between the least bone volume fraction required for the observation of nonoverlapping waves and the degree of anisotropy: The higher the DA, the lower the least BV/TV.

Velocity dispersion in trabecular bone: influence of multiple scattering and of absorption.

Speed of sound measurements are widely used clinically to assess bone strength. Trabecular bone is an attenuating composite material in which negative values of velocity dispersion have been measured, this behavior remaining poorly explained physically. The aim of this work is to describe the ultrasonic propagation in trabecular bone modeled by infinite cylinders immersed in a saturating matrix, and to derive the physical determinants of velocity dispersion. A homogenization model accounting for the coupling of multiple scattering and absorption phenomena allows the computation of phase velocity and of dispersion while varying bone properties. The present model is adapted from the generalized self-consistent method developed in the work of Yang and Mal [(1994). "Multiple-scattering of elastic waves in a fiber-reinforced composite," J. Mech. Phys. Solids 42, 1945-1968]. It predicts negative values of velocity dispersion, in agreement with experimental results obtained in phantoms mimicking trabecular bone. In trabecular bone, mostly negative and also positive values of velocity dispersion are predicted by the model, which span within the range of values measured experimentally. Scattering effects are responsible for the negative values of dispersion, whereas the frequency dependence of the absorption coefficient in bone marrow and/or in the trabeculae results in an increase in dispersion, which may then become positive.