Relationships among calcaneal backscatter, attenuation, sound speed, hip bone mineral density, and age in normal adult women

The present study was undertaken in order to investigate the use of calcaneal ultrasonic backscatter for the application of diagnosis of osteoporosis. Broadband ultrasonic attenuation (BUA), speed of sound (SOS), the average backscatter coefficient (ABC), and the hip bone mineral density (BMD) were measured in calcanea in 47 women (average age: 58 years, standard deviation: 13 years). All three ultrasound variables had comparable correlations with hip BMD (around 0.5). As reported previously by others, BUA and SOS were rather highly correlated with each other. The logarithm of the ABC was only moderately correlated with the other two. The three ultrasound parameters exhibited similar moderate negative correlations with age. These results taken collectively suggest that the ABC may carry important diagnostic information independent of that contained in BUA and SOS and, therefore, may be useful as an adjunct measurement in the diagnosis of osteoporosis.     

Correlations between acoustic properties and bone density in bovine cancellous bone from 0.5 to 2 MHz

Correlations between acoustic properties and bone density were investigated in the 12 defatted bovine cancellous bone specimens in vitro. Speed of sound (SOS) and broadband ultrasonic attenuation (BUA) were measured in three different frequency bandwidths from 0.5 to 2 MHz using three matched pairs of transducers with the center frequencies of 1, 2.25, and 3.5 MHz. The relative orientation between ultrasonic beam and bone specimen was the mediolateral (ML) direction of the bovine tibia. SOS shows significant linear positive correlation with apparent density for all three pairs of transducers. However, BUA shows relatively weak correlation with apparent density. SOS and BUA are only weakly correlated with each other. The linear combination of SOS and BUA in a multiple regression model leads to a significant improvement in predicting apparent density. The correlations among SOS, BUA, and bone density can be effectively and clearly represented in the three-dimensional space by the multiple regression model. These results suggest that the frequency range up to 1.5 MHz and the multiple regression model in the three-dimensional space can be useful in the osteoporosis diagnosis.     

Influence of microarchitecture alterations on ultrasonic backscattering in an experimental simulation of bovine cancellous bone aging

An experimental model which can simulate physical changes that occur during aging was developed in order to evaluate the effects of change of mineral content and microstructure on ultrasonic properties of bovine cancellous bone. Timed immersion in hydrochloric acid was used to selectively alter the mineral content. Scanning electron microscopy and histological staining of the acid-treated trabeculae demonstrated a heterogeneous structure consisting of a mineralized core and a demineralized layer. The presence of organic matrix contributed very little to normalized broadband ultrasound attenuation (nBUA) and speed of sound. All three ultrasonic parameters, speed of sound, nBUA and backscatter coefficient, were sensitive to changes in apparent density of bovine cancellous bone. A two-component model utilizing a combination of two autocorrelation functions (a densely populated model and a spherical distribution) was used to approximate the backscatter coefficient. The predicted attenuation due to scattering constituted a significant part of the measured total attenuation (due to both scattering and absorption mechanisms) for bovine cancellous bone. Linear regression, performed between trabecular thickness values and estimated from the model correlation lengths, showed significant linear correlation, with R(2)=0.81 before and R(2)=0.80 after demineralization. The accuracy of estimation was found to increase with trabecular thickness.     

The finite element method for micro-scale modeling of ultrasound propagation in cancellous bone

Quantitative ultrasound for bone assessment is based on the correlations between ultrasonic parameters and the properties (mechanical and physical) of cancellous bone. To elucidate the correlations, understanding the physics of ultrasound in cancellous bone is demanded. Micro-scale modeling of ultrasound propagation in cancellous bone using the finite-difference time-domain (FDTD) method has been so far utilized as one of the approaches in this regard. However, the FDTD method accompanies two disadvantages: staircase sampling of cancellous bone by finite difference grids leads to generation of wave artifacts at the solid–fluid interface inside the bone; additionally, this method cannot explicitly satisfy the needed perfect-slip conditions at the interface. To overcome these disadvantages, the finite element method (FEM) is proposed in this study. Three-dimensional finite element models of six water-saturated cancellous bone samples with different bone volume were created. The values of speed of sound (SOS) and broadband ultrasound attenuation (BUA) were calculated through the finite element simulations of ultrasound propagation in each sample. Comparing the results with other experimental and simulation studies demonstrated the capabilities of the FEM for micro-scale modeling of ultrasound in water-saturated cancellous bone.     

超声定量诊断骨质疏松症的方法研究

骨质疏松症是危害老龄化社会的常见疾病。本研究使用特殊结构设计的超声波探头,利用定量超声（QUS）技术测量胫骨中皮质骨的超声速度（SOS）,根据其所反映的骨密度信息,将可从一种新的角度评估人体的骨质量,为诊断骨质疏松症的临床应用提供一种新的诊断途径。     

Attenuation in trabecular bone: A comparison between numerical simulation and experimental results in human femur

Numerical simulations (finite-difference time domain) are compared to experimental results of ultrasound wave propagation through human trabecular bones. Three-dimensional high-resolution microcomputed tomography reconstructions served as input geometry for the simulation. The numerical simulation took into account scattering, but not absorption. Simulated and experimental values of the attenuation coefficients (alpha, dB/cm) and the normalized broadband ultrasound attenuation (nBUA, dB/cm/MHz) were measured and compared on a set of 28 samples. While experimental and simulated nBUA values were highly correlated (R(2)=0.83), and showed a similar dependence with bone volume fraction, the simulation correctly predicted experimental nBUA values only for low bone volume fraction (BV/TV). Attenuation coefficients were underestimated by the simulation. The absolute difference between experimental and simulated alpha values increased with both BV/TV and frequency. As a function of frequency, the relative difference between experimental and simulated alpha values decreased from 60% around 400 kHz to 30% around 1.2 MHz. Under the assumption that the observed discrepancy expresses the effect of the absorption, our results suggests that nBUA and its dependence on BV/TV can be mostly explained by scattering, and that the relative contribution of scattering to alpha increases with frequency, becoming predominant (>50 %) over absorption for frequencies above 600 kHz.     

Relationships of quantitative ultrasound parameters with cancellous bone microstructure in human calcaneus in vitro

Ultrasound parameters (attenuation, phase velocity, and backscatter), bone mineral density (BMD), and microarchitectural features were measured on 29 human cancellous calcaneus samples in vitro. Regression analysis was performed to predict ultrasound parameters from BMD and microarchitectural features. The best univariate predictors of the ultrasound parameters were the indexes of bone quantity: BMD and bone volume fraction (BV/TV). The most predictive univariate models for attenuation, phase velocity, and backscatter coefficient yielded adjusted squared correlation coefficients of 0.69-0.73. Multiple regression models yielded adjusted correlation coefficients of 0.74-0.83. Therefore attenuation, phase velocity, and backscatter are primarily determined by bone quantity, but multiple regression models based on bone quantity plus microarchitectural features achieve slightly better predictive performance than models based on bone quantity alone.     

Detection of bone disease with ultrasound--comparison with bone densitometry

A system for ultrasonic in-vivo examination of a heel bone (calcaneus) was developed. When operating in transmission mode, the system can measure broadband ultrasonic attenuation-BUA, speed of sound--SOS and thickness of bone. BUA and SOS are measured by comparing the pulses transmitted through the heel with the reference pulse transmitted through water. In our approach, we operate in the backscattered mode in addition to transmission. The backscattered ultrasonic technique for bone characterization is very promising because the magnitude of backscattered waves depends on the scattering cross-section of a trabecular structure that, to some extent, describes the microarchitecture of a calcaneus. Additionally, when the backscattered and transmitted signals are compared, some of the signal distortions caused by tissue and bone interfaces are reduced. A set of data representing signals transmitted through the heel and reflected inside a calcaneus for patients with osteoporosis was collected. Several signal-processing techniques were applied in order to smooth the backscattered signal and to calculate a trabecular structure cros-section (TSC) function. Results obtained by these approaches along with a spectral shift method and a standard BUA measurement are presented and compared to X-ray bone mineral density determination results.     

A numerical method to predict the effects of frequency-dependent attenuation and dispersion on speed of sound estimates in cancellous bone

Many studies have demonstrated that time-domain speed-of-sound (SOS) measurements in calcaneus are predictive of osteoporotic fracture risk. However, there is a lack of standardization for this measurement. Consequently, different investigators using different measurement systems and analysis algorithms obtain disparate quantitative values for calcaneal SOS, impairing and often precluding meaningful comparison and/or pooling of measurements. A numerical method has been developed to model the effects of frequency-dependent attenuation and dispersion on transit-time-based SOS estimates. The numerical technique is based on a previously developed linear system analytic model for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The numerical approach is somewhat more general in that it can be used to predict the effects of arbitrary pulse shapes and dispersion relationships. The numerical technique, however, utilizes several additional assumptions (compared with the analytic model) which would be required for the practical task of correcting existing clinical databases. These include a single dispersion relationship for all calcaneus samples, a simple linear model relating phase velocity to broadband ultrasonic attenuation, and a constant calcaneal thickness. Measurements on a polycarbonate plate and 30 human calcaneus samples were in good quantitative agreement with numerical predictions. In addition, the numerical approach predicts that in cancellous bone, frequency-dependent attenuation tends to be a greater contributor to variations in transit-time-based SOS estimates than dispersion. This approach may be used to adjust previously acquired individual measurements so that SOS data recorded with different devices using different algorithms may be compared in a meaningful fashion.     

Comparison study of photoacoustic and ultrasound spectrum analysis in osteoporosis detection

Osteoporosis is a progressive bone disease,which is characterized by a decrease in the bone mass and deterioration in bone micro-architecture.In theory,photoacoustic(PA) analysis has the potential to obtain the characteristics of the bone effectively.In this study,we try to compare the PA spectral analysis(PASA) method with the quantitative ultrasound(QUS) method in osteoporosis assessment.We compare the quantified parameter slope from the PASA and broadband ultrasound attenuation from QUS among different bone models,respectively.Both the simulation and ex vivo experiment results show that bone with lower bone mineral density has the higher slope in the PASA method.Our comparison study proves that the PASA method has the same efficiency as QUS in osteoporosis assessment.     

Effect of bone cortical thickness on velocity measurements using ultrasonic axial transmission: a 2D simulation study

In recent years, quantitative ultrasound (QUS) has played an increasing role in the assessment of bone status. The axial transmission technique allows to investigate skeletal sites such as the cortical layer of long bones (radius, tibia), inadequate to through-transmission techniques. Nevertheless, the type of propagation involved along bone specimens has not been clearly elucidated. Axial transmission is investigated here by means of two-dimensional simulations at 1 MHz. We focus our interest on the apparent speed of sound (SOS) of the first arriving signal (FAS). Its dependence on the thickness of the plate is discussed and compared to previous work. Different time criteria are used to derive the apparent SOS of the FAS as a function of source-receiver distance. Frequency-wave number analysis is performed in order to understand the type of propagation involved. For thick plates (thickness>lambdabone, longitudinal wavelength in bone), and for a limited range of source-receiver distances, the FAS corresponds to the lateral wave. Its velocity equals the longitudinal bulk velocity of the bone. For plate thickness less than lambdabone, some plate modes contribute to the FAS, and the apparent SOS decreases with the thickness in a way that depends on both the time criterion and on the source-receiver distance. The FAS corresponds neither to the lateral wave nor to a single plate mode. For very thin plates (thickness< lambdabone/4), the apparent SOS tends towards the velocity of the lowest order symmetrical vibration mode (S0 Lamb mode).     

Trabecular bone volume fraction measurements of a large number of subjects using a compact MRI

Trabecular bone volume fraction (TBVF) and speed of sound (SOS) were measured for the right calcanei of 416 female volunteers. The TBVF was measured with a compact MRI developed in our laboratory. The SOS was measured with a commercial quantitative ultrasound system. It was observed that the correlation coefficient between TBVF and SOS and that between TBVF and age varied depending on the location of region of interest (ROI) in the calcaneus. As a result, an optimum circular ROI with a diameter of 20 mm was determined so that the correlation coefficients were maximized. In the optimum ROI, transverse relaxation time (T₂) of the bone marrow protons of the calcaneus was found to be concentrated in a narrow range over the subjects. This result suggested that a 50% scan time reduction in the TBVF measurements could be made by skipping the T₂ correction procedure.     

On the estimation of backscatter coefficients using single-element focused transducers

The ultimate goal of quantitative ultrasound (QUS) imaging methods based on backscatter coefficient (BSC) estimates is to obtain system-independent structural information about samples. In the current study, three BSC estimation methods were compared and evaluated using the same backscattered pressure datasets in order to assess their consistency. BSC estimates were obtained from two phantoms with embedded glass spheres and compared to theoretical BSCs calculated using size distributions estimated using optical microscopy. Effective scatterer diameter and concentration estimates of the glass spheres were also obtained from the estimated BSCs. One estimation method needed to be compensated by more than an order of magnitude in amplitude in order to produce BSCs comparable to the other two methods. All calibration methods introduced different frequency-dependent effects, which could have noticeable effects on the bias of QUS estimates derived from experimental BSCs. Although in most cases the experimental QUS estimates obtained with all three methods were observed to differ by less than 10%, larger differences are expected depending on both the pressure focusing gain of the transducer (proportional to the ratio of the square of the aperture radius to the product of the wavelength and focal length) and ka range used in the estimation.     

A hybrid FDTD-Rayleigh integral computational method for the simulation of the ultrasound measurement of proximal femur

The development of novel quantitative ultrasound (QUS) techniques to measure the hip is critically dependent on the possibility to simulate the ultrasound propagation. One specificity of hip QUS is that ultrasounds propagate through a large thickness of soft tissue, which can be modeled by a homogeneous fluid in a first approach. Finite difference time domain (FDTD) algorithms have been widely used to simulate QUS measurements but they are not adapted to simulate ultrasonic propagation over long distances in homogeneous media. In this paper, an hybrid numerical method is presented to simulate hip QUS measurements. A two-dimensional FDTD simulation in the vicinity of the bone is coupled to the semi-analytic calculation of the Rayleigh integral to compute the wave propagation between the probe and the bone. The method is used to simulate a setup dedicated to the measurement of circumferential guided waves in the cortical compartment of the femoral neck. The proposed approach is validated by comparison with a full FDTD simulation and with an experiment on a bone phantom. For a realistic QUS configuration, the computation time is estimated to be sixty times less with the hybrid method than with a full FDTD approach.     

Temperature dependent ultrasonic characterization of biological media

Quantitative ultrasound (QUS) is an imaging technique that can be used to quantify tissue microstructure giving rise to scattered ultrasound. Other ultrasonic properties, e.g., sound speed and attenuation, of tissues have been estimated versus temperature elevation and found to have a dependence with temperature. Therefore, it is hypothesized that QUS parameters may be sensitive to changes in tissue microstructure due to temperature elevation. Ultrasonic backscatter experiments were performed on tissue-mimicking phantoms and freshly excised rabbit and beef liver samples. The phantoms were made of agar and contained either mouse mammary carcinoma cells (4T1) or chinese hamster ovary cells (CHO) as scatterers. All scatterers were uniformly distributed spatially at random throughout the phantoms. All the samples were scanned using a 20-MHz single-element f/3 transducer. Quantitative ultrasound parameters were estimated from the samples versus increases in temperature from 37 °C to 50 °C in 1 °C increments. Two QUS parameters were estimated from the backscatter coefficient [effective scatterer diameter (ESD) and effective acoustic concentration (EAC)] using a spherical Gaussian scattering model. Significant increases in ESD and decreases in EAC of 20%-40% were observed in the samples over the range of temperatures examined. The results of this study indicate that QUS parameters are sensitive to changes in temperature.     

Amplitude modulation excitation for cancellous bone evaluation using a portable ultrasonic backscatter instrumentation

The ultrasonic backscatter (UB) has the advantage of non-invasively obtaining bone density and structure, expected to be an assessment tool for early diagnosis osteoporosis. All former UB measurements were based on exciting a short single-pulse and analyzing the ultrasonic signals backscattered in bone. This study aims to examine amplitude modulation (AM) ultrasonic excitation with UB measurements for predicting bone characteristics. The AM multiple lengths excitation and backscatter measurement (AM-UB) functions were integrated into a portable ultrasonic instrument for bone characterization. The apparent integrated backscatter coefficient in the AM excitation (AIB_AM) was evaluated on the AM-UB instrumentation. The correlation coefficients of the AIB_AM estimating volume fraction (BV/TV), structure model index (SMI), and bone mineral density (BMD) were then analyzed. Significant correlations (|R| = 0.82-0.93, p < 0.05) were observed between the AIB_AM, BV/TV, SMI, and BMD. By growing the AM excitation length, the AIB_AM values exhibit more stability both in 1.0-MHz and 3.5-MHz measurements. The recommendations in AM-UB measurement were that the avoided length (T1) should be lower than AM excitation length, and the analysis length (T2) should be enough long but not more than AM excitation length. The authors conducted an AM-UB measurement for cancellous bone characterization. Increasing the AM excitation length could substantially enhance AIB_AM values stability with varying analyzed signals. The study suggests the portable AM-UB instrument with the integration of real-time analytics software that might provide a potential tool for osteoporosis early screening.     

Relative contributions of porosity and mineralized matrix properties to the bulk axial ultrasonic wave velocity in human cortical bone

Velocity of ultrasound waves has proved to be a useful indicator of bone biomechanical competence. A detailed understanding of the dependence of ultrasound parameters such as velocity on bone characteristics is a key to the development of bone quantitative ultrasound (QUS). The objective of this study is to investigate the relative contributions of porosity and mineralized matrix properties to the bulk compressional wave velocity (BCV) along the long bone axis. Cross-sectional slabs from the diaphysis of four human femurs were included in the study. Seven regions of interest (ROIs) were selected in each slab. BCV was measured in through-transmission at 5 MHz. Impedance of the mineralized matrix (Z_m) and porosity (Por) were obtained from 50 MHz scanning acoustic microscopy. Por and Z_m had comparable effects on BCV along the bone axis (R = −0.57 and R = 0.72, respectively).     

Numerical investigation of ultrasound reflection and backscatter measurements in cancellous bone on various receiving areas

In this study, new ultrasound reflection and backscatter measurements in cancellous bone using a membrane-type hydrophone are proposed. A membrane hydrophone made of a piezoelectric polymer film mounted on an annular frame allows an incident ultrasound wave to pass through its aperture because it has no backing material. Therefore, in measurements using the membrane hydrophone, the receiving area could be located independently from the transmitting area. In addition, the size and shape of the receiving area, which corresponded to those of the electrode deposited on the piezoelectric film, could be arranged in various ways. To investigate the validity of the proposed measurements, before bench-top experiments, the reflected and backscattered waves from cancellous bone were numerically simulated using a finite-difference time-domain method. The reflection and backscatter parameters were measured on various receiving areas, and their correlation coefficients with the structural parameters in the cancellous bone were derived. The simulated results suggested that appropriate receiving areas for the reflection and backscatter measurements could exist and that the proposed measurements could be more effective for evaluating bone properties than conventional measurements.     

超声背散射法评价松质骨状况的研究

超声背散射法评价松质骨状况及诊断骨质疏松症是近年来医学超声领域内的研究热点之一,现已取得了显著的进展。本文将介绍近年来超声背散射法及其参量评价松质骨状况的研究进展,并分析超声背散射相关参量频谱质心偏移量（SCS）和平均骨小梁间距（TbSp）与骨矿密度（BMD）的相关性。研究结果表明,超声背散射参量与BMD有较高的相关性。最后提出了将来研究中需要努力的方向。