The respective and dependent effects of scattering and bone matrix absorption on ultrasound attenuation in cortical bone.

Cortical bone is characterized by a dense solid matrix permeated by fluid-filled pores. Ultrasound scattering has potential for the non-invasive evaluation of changes in bone porosity. However, there is an incomplete understanding of the impact of ultrasonic absorption in the solid matrix on ultrasound scattering. In this study, maps were derived from scanning acoustic microscopy images of human femur cross-sections. Finite-difference time domain ultrasound scatter simulations were conducted on these maps. Pore density, diameter distribution of the pores, and nominal absorption values in the solid and fluid matrices were controlled. Ultrasound pulses with a central frequency of 8.2 MHz were propagated, both in through-transmission and backscattering configurations. From these data, the scattering, bone matrix absorption, and attenuation extinction lengths were calculated. The results demonstrated that as absorption in the solid matrix was varied, the scattering, absorption, and attenuation extinction lengths were significantly impacted. It was shown that for lower values of absorption in the solid matrix (less than 2 dB mm-1), attenuation due to scattering dominates, whereas at higher values of absorption (more than 2 dB mm-1), attenuation due to absorption dominates. This will impact how ultrasound attenuation and scattering parameters can be used to extract quantitative information on bone microstructure.

Focused Low-Intensity Pulsed Ultrasound (FLIPUS) Mitigates Apoptosis of MLO-Y4 Osteocyte-like Cells.

Long cytoplasmic processes of osteocytes orchestrate bone activity by integration of biochemical and mechanical signals and regulate load-induced bone adaptation. Low-Intensity Pulsed Ultrasound (LIPUS) is a clinically used technique for fracture healing that delivers mechanical impulses to the damaged bone tissue in a non-invasive and non-ionizing manner. The mechanism of action of LIPUS is still controversially discussed in the scientific community. In this study, the effect of focused LIPUS (FLIPUS) on the survival of starved MLO-Y4 osteocytes was investigated in vitro. Osteocytes stimulated for 10 min with FLIPUS exhibited extended dendrites, which formed frequent connections to neighboring cells and spanned longer distances. The sonicated cells displayed thick actin bundles and experienced increase in expression of connexin 43 (Cx43) proteins, especially on their dendrites, and E11 glycoprotein, which is responsible for the elongation of cellular cytoplasmic processes. After stimulation, expression of cell growth and survival genes as well as genes related to cell-cell communication was augmented. In addition, cell viability was improved after the sonication, and a decrease in ATP release in the medium was observed. In summary, FLIPUS mitigated apoptosis of starved osteocytes, which is likely related to the formation of the extensive dendritic network that ensured cell survival.

Bi-Directional Axial Transmission measurements applied in a clinical environment.

Accurate measurement of cortical bone parameters may improve fracture risk assessment and help clinicians on the best treatment strategy. Patients at risk of fracture are currently detected using the current X-Ray gold standard DXA (Dual XRay Absorptiometry). Different alternatives, such as 3D X-Rays, Magnetic Resonance Imaging or Quantitative Ultrasound (QUS) devices, have been proposed, the latter having advantages of being portable and sensitive to mechanical and geometrical properties. The objective of this cross-sectional study was to evaluate the performance of a Bi-Directional Axial Transmission (BDAT) device used by trained operators in a clinical environment with older subjects. The device, positioned at one-third distal radius, provides two velocities: VFAS (first arriving signal) and VA0 (first anti-symmetrical guided mode). Moreover, two parameters are obtained from an inverse approach: Ct.Th (cortical thickness) and Ct.Po (cortical porosity), along with their ratio Ct.Po/Ct.Th. The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. One hundred and six patients (81 women, 25 men) from Marien Hospital and St. Anna Hospital (Herne, Germany) were included in this study. Age ranged from 41 to 95 years, while body mass index (BMI) ranged from 16 to 47 kg.m-2. Three groups were considered: 79 non-fractured patients (NF, 75±13years), 27 with non-traumatic fractures (F, 80±9years) including 14 patients with non-vertebral fractures (NVF, 84±7years). Weak to moderate significant Spearman correlations (R ranging from 0.23 to 0.53, p < 0.05) were found between ultrasound parameters and age, BMI. Using multivariate Partial Least Square discrimination analyses with Leave-One-Out Cross-Validation (PLS-LOOCV), we found the combination of VFAS and the ratio Ct.Po/Ct.Th to be predictive for all non traumatic fractures (F) with the odds ratio (OR) equals to 2.5 [1.6-3.4] and the area under the ROC curve (AUC) equal to 0.63 [0.62-0.65]. For the group NVF, combination of four parameters VA0. Ct.Th, Ct.Po and Ct.Po/Ct.Po, along with age provides a discrimination model with OR and AUC equals to 7.5 [6.0-9.1] and 0.75 [0.73-0.76]. When restricted to a smaller population (87 patients) common to both BDAT and DXA, BDAT ORs and AUCs are comparable or slightly higher to values obtained with DXA. The fracture risk assessment by BDAT method in older patients, in a clinical setting, suggests the benefit of the affordable and transportable device for the routine use.

A Tissue Engineering Acoustophoretic (TEA) Set-up for the Enhanced Osteogenic Differentiation of Murine Mesenchymal Stromal Cells (mMSCs).

Quickly developing precision medicine and patient-oriented treatment strategies urgently require novel technological solutions. The randomly cell-populated scaffolds usually used for tissue engineering often fail to mimic the highly anisotropic characteristics of native tissue. In this work, an ultrasound standing-wave-based tissue engineering acoustophoretic (TEA) set-up was developed to organize murine mesenchymal stromal cells (mMSCs) in an in situ polymerizing 3-D fibrin hydrogel. The resultant constructs, consisting of 17 cell layers spaced at 300 µm, were obtained by continuous wave ultrasound applied at a 2.5 MHz frequency. The patterned mMSCs preserved the structured behavior within 10 days of culturing in osteogenic conditions. Cell viability was moderately increased 1 day after the patterning; it subdued and evened out, with the cells randomly encapsulated in hydrogels, within 21 days of culturing. Cells in the structured hydrogels exhibited enhanced expression of certain osteogenic markers, i.e., Runt-related transcription factor 2 (RUNX2), osterix (Osx) transcription factor, collagen-1 alpha1 (COL1A1), osteopontin (OPN), osteocalcin (OCN), and osteonectin (ON), as well as of certain cell-cycle-progression-associated genes, i.e., Cyclin D1, cysteine-rich angiogenic inducer 61 (CYR61), and anillin (ANLN), when cultured with osteogenic supplements and, for ANLN, also in the expansion media. Additionally, OPN expression was also augmented on day 5 in the patterned gels cultured without the osteoinductive media, suggesting the pro-osteogenic influence of the patterned cell organization. The TEA set-up proposes a novel method for non-invasively organizing cells in a 3-D environment, potentially enhancing the regenerative properties of the designed anisotropic constructs for bone healing.

Quantitative Ultrasound Assessment of Early Osteoarthritis in Human Articular Cartilage Using a High-Frequency Linear Array Transducer.

Quantitative ultrasound (QUS) assessment of osteoarthritis (OA) using high-frequency, research-grade single-element ultrasound systems has been reported. The objective of this ex vivo study was to assess the performance of QUS in detecting early OA using a high-frequency linear array transducer. Osteochondral plugs (n = 26) of human articular cartilage were scanned with ExactVu Micro-Ultrasound using an EV29L side-fire transducer. For comparison, the samples were also imaged with SAM200Ex, a custom 40-MHz scanning acoustic microscope with a single-element, focused transducer. Thirteen QUS parameters were derived from the ultrasound data. Magnetic resonance imaging (MRI) data, with T1 and T2 extracted as the quantitative parameters, were also acquired for comparison. Cartilage degeneration was graded from histology and correlated to all quantitative parameters. A maximum Spearman rank correlation coefficient (ρ) of 0.75 was achieved using a combination of ExactVu QUS parameters, while a maximum ρ of 0.62 was achieved using a combination of parameters from SAM200Ex. A maximum ρ of 0.75 was achieved using the T1 and T2 MRI parameters. This study illustrates the potential of a high-frequency linear array transducer to provide a convenient method for early OA screening with results comparable to those of research-grade single-element ultrasound and MRI.

Clinical Devices for Bone Assessment.

Although it has been over 30 years since the first recorded use of quantitative ultrasound (QUS) technology to predict bone strength, the field has not yet reached its maturity. Among several QUS technologies available to measure cortical or cancellous bone sites, at least some of them have demonstrated potential to predict fracture risk with an equivalent efficiency compared to X-ray densitometry techniques, and the advantages of being non-ionizing, inexpensive, portable, highly acceptable to patients and repeatable. In this Chapter, we review instrumental developments that have led to in vivo applications of bone QUS, emphasizing the developments occurred in the decade 2010-2020. While several proposals have been made for practical clinical use, there are various critical issues that still need to be addressed, such as quality control and standardization. On the other side, although still at an early stage of development, recent QUS approaches to assess bone quality factors seem promising. These include guided waves to assess mechanical and structural properties of long cortical bones or new QUS technologies adapted to measure the major fracture sites (hip and spine). New data acquisition and signal processing procedures are prone to reveal bone properties beyond bone mineral quantity and to provide a more accurate assessment of bone strength.

Pore-Size Distribution and Frequency-Dependent Attenuation in Human Cortical Tibia Bone Discriminate Fragility Fractures in Postmenopausal Women With Low Bone Mineral Density.

Osteoporosis is a disorder of bone remodeling leading to reduced bone mass, structural deterioration, and increased bone fragility. The established diagnosis is based on the measurement of areal bone mineral density by dual-energy X-ray absorptiometry (DXA), which poorly captures individual bone loss and structural decay. Enlarged cortical pores in the tibia have been proposed to indicate structural deterioration and reduced bone strength in the hip. Here, we report for the first time the in vivo assessment of the cortical pore-size distribution together with frequency-dependent attenuation at the anteromedial tibia midshaft by means of a novel ultrasonic cortical backscatter (CortBS) technology. We hypothesized that the CortBS parameters are associated with the occurrence of fragility fractures in postmenopausal women (n = 55). The discrimination performance was compared with those of DXA and high-resolution peripheral computed tomography (HR-pQCT). The results suggest a superior discrimination performance of CortBS (area under the receiver operating characteristic curve [AUC]: 0.69 ≤ AUC ≤ 0.75) compared with DXA (0.54 ≤ AUC ≤ 0.55) and a similar performance compared with HR-pQCT (0.66 ≤ AUC ≤ 0.73). CortBS is the first quantitative bone imaging modality that can quantify microstructural tissue deteriorations in cortical bone, which occur during normal aging and the development of osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Estimation of Cortical Bone Microstructure From Ultrasound Backscatter.

Multichannel 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 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 (six 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 a 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 noninvasive 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, nonionizing measurement system could have a major impact on preventing osteoporotic fractures.

Bulk Wave Velocities in Cortical Bone Reflect Porosity and Compression Strength.

The goal of this study was to evaluate whether ultrasonic velocities in cortical bone can be considered as a proxy for mechanical quality of cortical bone tissue reflected by porosity and compression strength. Micro-computed tomography, compression mechanical testing and resonant ultrasound spectroscopy were used to assess, respectively, porosity, strength and velocity of bulk waves of both shear and longitudinal polarisations propagating along and perpendicular to osteons, in 92 cortical bone specimens from tibia and femur of elderly human donors. All velocities were significantly associated with strength (r = 0.65-0.83) and porosity (r = -0.64 to -0.77). Roughly, according to linear regression models, a decrease in velocity of 100 m/s corresponded to a loss of 20 MPa in strength (which is approximately 10% of the largest strength value) and to an increase in porosity of 5%. These results provide a rationale for the in vivo measurement of one or several velocities for the diagnosis of bone fragility.

High frequency ultrasound assesses transient changes in cartilage under osmotic loading.

High-frequency ultrasound is used in this study to measure noninvasively, by means of osmotic loading, changes in speed of sound and cartilage thickness caused by variations of the salt concentration in the external bath. Articular cartilage comprises three main structural components: Water, collagen fibrils and proteoglycan macromolecules carrying negative charges. The negatively charged groups of proteoglycans attract cations and water into tissue and govern its shrinkage/swelling behavior, which is a fundamental mechano-electrochemical function of cartilage tissue. In this study, the mechano-electrochemical behavior of cartilage is modeled by a diffusion model. The proposed model enables simulations of cartilage osmotic loading under various parameter settings and allows to quantify cartilage mechanical properties. This theoretical model is derived from the kinetic theory of diffusion. The objectives of the study are to quantify time dependent changes in cartilage thickness, and in speed of sound within tissue with help of the finite element based simulations and data from experiments. Experimental data are obtained from fresh and trypsinized ovine patella samples. Results show that the proposed diffusion model is capable to describe transient osmotic loading of cartilage. Mean values and their deviations of the relative changes of cartilage characteristics in response to chemical loading are presented.

Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH).

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.

Cortical thinning and accumulation of large cortical pores in the tibia reflect local structural deterioration of the femoral neck.

INTRODUCTION: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck. METHODS: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 µm voxel size. Cortical thickness (Ct.Thtibia), porosity (Ct.Potibia) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 µm pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models. RESULTS: Femur strength was associated with the total (vBMDtot; R2 = 0.23, p < 0.01) and trabecular (vBMDtrab; R2 = 0.26, p < 0.01) volumetric bone mineral density (vBMD), with the cortical thickness (Ct.ThFN; R2 = 0.29, p < 0.001) and with the trabecular bone volume fraction (Tb.BV/TVFN; R2 = 0.34, p < 0.001), separation (Tb.SpFN; R2 = 0.25, p < 0.01) and number (Tb.NFN; R2 = 0.32, p < 0.001) of the femoral neck. Moreover, smaller Ct.Thtibia was associated with smaller Ct.ThFN (R2 = 0.31, p < 0.05), lower Tb.BV/TVFN (R2 = 0.29, p < 0.05), higher Tb.SpFN (R2 = 0.33, p < 0.05) and lower Tb.NFN (R2 = 0.42, p < 0.01). A higher prevalence of pores with diameter > 100 µm in tibial cortical bone (relCt.Po100µm-tibia) indicated higher Tb.SpFN (R2 = 0.36, p < 0.01) and lower Tb.NFN (R2 = 0.45, p < 0.01). CONCLUSION: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia.

Femur strength predictions by nonlinear homogenized voxel finite element models reflect the microarchitecture of the femoral neck.

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.

Estimation of Thickness and Speed of Sound in Cortical Bone Using Multifocus Pulse-Echo Ultrasound.

Most bone loss during the development of osteoporosis occurs in cortical bone at the peripheral skeleton. Decreased cortical thickness (Ct.Th) and the prevalence of large pores at the tibia are associated with reduced bone strength at the hip. Ct.Th and cortical sound velocity, i.e., a surrogate marker for changes of cortical porosity (Ct.Po), are key biomarkers for the identification of patients at high fracture risk. In this study, we have developed a method using a conventional ultrasound array transducer to determine thickness (Ct.Th) and the compressional sound velocity propagating in the radial bone direction (Ct. ν11 ) using a refraction-corrected multifocus imaging approach. The method was validated in-silico on porous bone plate models using a 2-D finite-difference time-domain method and ex vivo on plate-shaped plastic reference materials and on plate-shaped cortical bovine tibia samples. Plane-wave pulse-echo measurements provided reference values to assess precision and accuracy of our method. In-silico results revealed the necessity to account for inclination-dependent transmission losses at the bone surface. Moreover, the dependence of Ct. ν11 on both porosity and pore density was observed. Ct.Th and Ct. ν11 obtained ex vivo showed a high correlation ) with reference values. The ex-vivo accuracy and precision for Ct. ν11 were 29.9 m/s and 0.94%, respectively, and those for Ct.Th were 0.04 mm and 1.09%, respectively. In conclusion, this numerical and experimental study demonstrates an accurate and precise estimation of Ct.Th and Ct. ν11 . The developed multifocus technique may have high clinical potential to improve fracture risk prediction using noninvasive and nonionizing conventional ultrasound technology with image guidance.

Acoustic diffusion constant of cortical bone: Numerical simulation study of the effect of pore size and pore density on multiple scattering.

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) ∈[5-25] pore/mm2 and size (Ct.Po.Dm) ∈[30-100] µm 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.Po.Dm-1.49, R2=0.989 , p=4.96×10-5,RMSE=0.06; D=6.91Ct.Po.Dn-1.01, R2=0.94, p=2.8×10-3 , RMSE=0.09), suggesting the potential of the proposed technique for the characterization of the cortical microarchitecture.

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength.

[This corrects the article DOI: 10.1371/journal.pone.0215405.].

Large cortical bone pores in the tibia are associated with proximal femur strength.

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 (aBMDneck) 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 aBMDneck (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 aBMDneck, 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.

In Vivo Measurements of Cortical Thickness and Porosity at the Proximal Third of the Tibia Using Guided Waves: Comparison with Site-Matched Peripheral Quantitative Computed Tomography and Distal High-Resolution Peripheral Quantitative Computed Tomography.

The aim of this study was to estimate cortical porosity (Ct.Po) and cortical thickness (Ct.Th) using 500-kHz bi-directional axial transmission (AT). Ct.ThAT and Ct.PoAT were obtained at the tibia in 15 patients from a 2-D transverse isotropic free plate model fitted to measured guided wave dispersion curves. The velocities of the first arriving signal (υFAS) and A0 mode (υA0) were also determined. Site-matched peripheral quantitative computed tomography (pQCT) provided volumetric cortical bone mineral density (Ct.vBMDpQCT) and Ct.ThpQCT. Good agreement was found between Ct.ThAT and Ct.ThpQCT (R2 = 0.62, root mean square error [RMSE] = 0.39 mm). Ct.vBMDpQCT correlated with Ct.PoAT (R2 = 0.57), υFAS (R2 = 0.43) and υA0 (R2 = 0.28). Furthermore, a significant correlation was found between AT and distal high-resolution pQCT. The measurement ofcortical parameters at the tibia using guided waves might improve the prediction of bone fractures in a cost-effective and radiation-free manner.

Ex vivo cortical porosity and thickness predictions at the tibia using full-spectrum ultrasonic guided-wave analysis.

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 (υFAS) and A0 mode (υA0) 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 υA0 (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.