Multi-channel pulse-echo ultrasound using linear arrays and single-channel data acquisition systems opens new perspectives for the evaluation of cortical bone. In combination with spectral backscatter analysis, it can provide quantitative information about cortical microstructural properties. We present a numerical study, based on the finite-difference time-domain (FDTD) method, to estimate the backscatter cross-section of randomly distributed circular pores in a bone matrix. A model that predicts the backscatter coefficient using arbitrary pore diameter distributions was derived. In an ex-vivo study on 19 human tibia bones (6 males, 13 females, 83.7 ± 8.4 years), multidirectional ultrasound backscatter measurements were performed using an ultrasound scanner equipped with a 6-MHz 128-element linear array with sweep motor control. A normalized depth-dependent spectral analysis was performed to derive backscatter and attenuation coefficients. Site-matched reference values of tissue acoustic impedance Z, cortical thickness Ct.Th, pore density Ct.Po.Dn, porosity Ct.Po and characteristic parameters of the pore diameter (Ct.Po.Dm) distribution were obtained from 100-MHz scanning-acoustic microscopy images. Proximal femur areal bone mineral density (aBMD), stiffness S and ultimate force Fu from the same donors were available from a previous study. All pore structure and material properties could be predicted using linear combinations of backscatter parameters with median to high accuracy (0.28 ≤ adjusted R2 ≤ 0.59). The combination of cortical thickness and backscatter parameter provided similar or better prediction accuracies than aBMD. For the first time, a method for the non-invasive assessment of the pore diameter distribution in cortical bone by ultrasound is proposed. The combined assessment of cortical thickness, sound velocity, and pore size distribution in a mobile, non-ionizing measurement system could have a major impact to prevent osteoporotic fractures.

Summary The estimation of cortical thickness (Ct.Th) and porosity (Ct.Po) at the tibia using axial transmission ultrasound was successfully validated ex vivo against site-matched micro-computed tomography. The assessment of cortical parameters based on full-spectrum guided-wave analysis might improve the prediction of bone fractures in a cost-effective and radiation-free manner. Purpose Cortical thickness (Ct.Th) and porosity (Ct.Po) are key parameters for the identification of patients with fragile bones. The main objective of this ex vivo study was to validate the measurement of Ct.Po and Ct.Th at the tibia using a non-ionizing, low-cost, and portable 500-kHz ultrasound axial transmission system. Additional ultrasonic velocities and site-matched reference parameters were included in the study to broaden the analysis. Methods Guided waves were successfully measured ex vivo in 17 human tibiae using a novel 500-kHz bi-directional axial transmission probe. Theoretical dispersion curves of a transverse isotropic free plate model with invariant matrix stiffness were fitted to the experimental dispersion curves in order to estimate Ct.Th and Ct.Po. In addition, the velocities of the first arriving signal (υ_FAS) and A₀ mode (υ_A0) were measured. Reference Ct.Po, Ct.Th, and vBMD were obtained from site-matched micro-computed tomography. Scanning acoustic microscopy (SAM) provided the acoustic impedance of the axial cortical bone matrix. Results The best predictions of Ct.Po (R² = 0.83, RMSE = 2.2%) and Ct.Th (R² = 0.92, RMSE = 0.2 mm, one outlier excluded) were obtained from the plate model. The second best predictors of Ct.Po and Ct.Th were vBMD (R² = 0.77, RMSE = 2.6%) and υ_A0 (R² = 0.28, RMSE = 0.67 mm), respectively. Conclusions Ct.Th and Ct.Po were accurately predicted at the human tibia ex vivo using a transverse isotropic free plate model with invariant matrix stiffness. The model-based predictions were not further enhanced when we accounted for variations in axial tissue stiffness as reflected by the acoustic impedance from SAM.

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMD_neck) was measured by dual‐energy X‐ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMD_neck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMD_neck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.

While osteoporosis assessment has long focused on the characterization of trabecular bone, the cortical bone micro-structure also provides relevant information on bone strength. This numerical study takes advantage of ultrasound multiple scattering in cortical bone to investigate the effect of pore size and pore density on the acoustic diffusion constant. Finite-difference time-domain simulations were conducted in cortical microstructures that were derived from acoustic microscopy images of human proximal femur cross sections and modified by controlling the density (Ct.Po.Dn) $\in [5-25]\hspace{0.17em}p\mathit{ore}/m{m}^2$ and size (Ct.Po.Dm) $\in [30-100]\hspace{0.17em}\mu m$ of the pores. Gaussian pulses were transmitted through the medium and the backscattered signals were recorded to obtain the backscattered intensity. The incoherent contribution of the backscattered intensity was extracted to give access to the diffusion constant D. At 8 MHz, significant differences in the diffusion constant were observed in media with different porous micro-architectures. The diffusion constant was monotonously influenced by either pore diameter or pore density. An increase in pore size and pore density resulted in a decrease in the diffusion constant (D $=285.9Ct.\mathit{Po}.D{m}^{-1.49},\hspace{0.17em}{R}^2=0.989\hspace{0.17em},\hspace{0.17em}p=4.96\times {10}^{-5},\mathit{RMSE}=0.06;\hspace{0.17em}D=6.91Ct.\mathit{Po}.D{n}^{-1.01},\hspace{0.17em}{R}^2=0.94,\hspace{0.17em}p=2.8\times {10}^{-3}\hspace{0.17em},\hspace{0.17em}\mathit{RMSE}=0.09$ ), suggesting the potential of the proposed technique for the characterization of the cortical microarchitecture.

In the human femoral neck, the contribution of the cortical and trabecular architecture to mechanical strength is known to depend on the load direction. In this work, we investigate if QCT-derived homogenized voxel finite element (hvFE) simulations of varying hip loading conditions can be used to study the architecture of the femoral neck. The strength of 19 pairs of human femora was measured ex vivo using nonlinear hvFE models derived from high-resolution peripheral QCT scans (voxel size: 30.3 µm). Standing and side-backwards falling loads were modeled. Quasi-static mechanical tests were performed on 20 bones for comparison. Associations of femur strength with volumetric bone mineral density (vBMD) or microstructural parameters of the femoral neck obtained from high-resolution QCT were compared between mechanical tests and simulations and between standing and falling loads. Proximal femur strength predictions by hvFE models were positively associated with the vBMD of the femoral neck (R² > 0.61, p < 0.001), as well as with its cortical thickness (R² > 0.27, p < 0.001), trabecular bone volume fraction (R² = 0.42, p < 0.001) and with the first two principal components of the femoral neck architecture (R² > 0.38, p < 0.001). Associations between femur strength and femoral neck microarchitecture were stronger for one-legged standing than for side-backwards falling. For both loading directions, associations between structural parameters and femur strength from hvFE models were in good agreement with those from mechanical tests. This suggests that hvFE models can reflect the load-direction-specific contribution of the femoral neck microarchitecture to femur strength.