Bone mineral density value evaluation based on photoacoustic spectral analysis combined with deep learning method

The diagnosis of osteoporosis is eventually converted to the measurement of bone mineral density(BMD) in clinical trials.Since our previous work had proved the ability of using photoacoustic spectral analysis(PASA)to efficiently detect osteoporosis,in this contribution,we proposed a fully connected multi-layer deep neural network combined with PASA to semi-quantify BMD values corresponding to varying degrees of bone loss and to further evaluate the degree of osteoporosis.Experiments were carried out on swine femur heads,and the performance of our proposed method is satisfying for future clinical screening.     

Multi-frequency axial transmission bone ultrasonometer

The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis.     

Use of multiple acoustic wave modes for assessment of long bones: model study

Multiple acoustic wave mode method has been proposed as a new modality in axial bone QUS. The new method is based on measurement of ultrasound velocity at different ratio of wavelength to the bone thickness, and taking into account both bulk and guided waves. It allows assessment of changes in both the material properties related to porosity and mineralization as well as the cortical thickness influenced by resorption from inner layers, which are equally important in diagnostics of osteoporosis and other bone osteopenia. Developed method was validated in model studies using a dual-frequency (100 and 500 kHz) ultrasound device. Three types of bone phantoms for long bones were developed and tested: (1) tubular specimens from polymer materials to model combined changes of material stiffness and cortical wall thickness; (2) layered specimens to model porosity in compact bone progressing from endosteum towards periosteum; (3) animal bone specimens with both cortical and trabecular components. Observed changes of the ultrasound velocity of guided waves at 100 kHz followed gradual changes in the thickness of the intact cortical layer. On the other hand, the bulk velocity at 500 kHz remained nearly constant at the different cortical layer thickness but was affected by the material stiffness. Similar trends were observed in phantoms and in fragments of animal bones.     

On ultrasound waves guided by bones with coupled soft tissues: A mechanism study and in vitro calibration

The influence of soft tissues coupled with cortical bones on precision of quantitative ultrasound (QUS) has been an issue in the clinical bone assessment in conjunction with the use of ultrasound. In this study, the effect arising from soft tissues on propagation characteristics of guided ultrasound waves in bones was investigated using tubular Sawbones phantoms covered with a layer of mimicked soft tissue of different thicknesses and elastic moduli, and an in vitro porcine femur in terms of the axial transmission measurement. Results revealed that presence of soft tissues can exert significant influence on the propagation of ultrasound waves in bones, leading to reduced propagation velocities and attenuated wave magnitudes compared with the counterparts in a free bone in the absence of soft tissues. However such an effect is not phenomenally dependent on the variations in thickness and elastic modulus of the coupled soft tissues, making it possible to compensate for the coupling effect regardless of the difference in properties of the soft tissues. Based on an in vitro calibration, this study proposed quantitative compensation for the effect of soft tissues on ultrasound waves in bones, facilitating development of high-precision QUS.     

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.     

超声诊断骨质疏松症中松质骨的模型

骨质疏松症(OP)是老龄化社会中影响健康的一个重要问题，超声技术已成为诊断骨质疏松症的一种常用方法。文中综述了近年来用超声诊断骨质疏松症中松质骨模型研究的进展，对棒状模型、流体多孔介质模型(Biot理论)和层状模型(schoenberg理论)进行了分析和讨论，指出了各理论模型存在的缺陷，对下一步的研究工作提出了建议。     

Anisotropy of ultrasonic backscatter and attenuation from human calcaneus: implications for relative roles of absorption and scattering in determining attenuation

Although bone sonometry has been demonstrated to be useful in the diagnosis of osteoporosis, much remains to be learned about the processes governing the interactions between ultrasound and bone. In order to investigate these processes, ultrasonic attenuation and backscatter in two orientations were measured in 43 human calcaneal specimens in vitro at 500 kHz. In the mediolateral (ML) orientation, the ultrasound propagation direction is approximately perpendicular to the trabecular axes. In the anteroposterior (AP) orientation, a wide range of angles between the ultrasound propagation direction and trabecular axes is encountered. Average attenuation slope was 18% greater while average backscatter coefficient was 50% lower in the AP orientation compared with the ML orientation. Backscatter coefficient in both orientations approximately conformed to a cubic dependence on frequency, consistent with a previously reported model. These results support the idea that absorption is a greater component of attenuation than scattering in human calcaneal trabecular bone.     

In vitro ultrasonic characterization of human cancellous femoral bone using transmission and backscatter measurements: relationships to bone mineral density

Thirty-eight slices of pure trabecular bone 1-cm thickness were extracted from human proximal femurs. A pair of 1-MHz central frequency transducers was used to measure quantitative ultrasound (QUS) parameters in transmission [normalized broadband ultrasound attenuation (nBUA), speed of sound (SOS)] and in backscatter [broadband ultrasound backscatter (BUB)]. Bone mineral density (BMD) was measured using clinical x-ray quantitative computed tomography. Site-matched identical region of interest (ROIs) of 7 x 7 mm2 were positioned on QUS and QCT images. This procedure resulted in 605 ROIs for all the specimens data pooled together. The short-term precision of the technique expressed in terms of CV was found to be 2.3% for nBUA, 0.3% for SOS and 4.5% for BUB. Significant linear correlation between QUS and BMD were found for all the 605 ROIs pooled, with r2 values of 0.73, 0.77, and 0.58 for nBUA, SOS, and BUB, respectively (all p < 0.05). For the BUB, the best regression was obtained with a polynomial fit of second order (r2 = 0.63). An analysis of measurements errors was developed. It showed that the residual variability of SOS is almost completely predicted by measurements errors, which is not the case for BUA and BUB, suggesting a role for micro-architecture in the determination of BUA and BUB.     

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。     

Fabric dependence of quasi-waves in anisotropic porous media

Assessment of bone loss and osteoporosis by ultrasound systems is based on the speed of sound and broadband ultrasound attenuation of a single wave. However, the existence of a second wave in cancellous bone has been reported and its existence is an unequivocal signature of poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as bone mineral density (BMD), a fabric-dependent anisotropic poroelastic wave propagation theory was recently developed for pure wave modes propagating along a plane of symmetry in an anisotropic medium. Key to this development was the inclusion of the fabric tensor--a quantitative stereological measure of the degree of structural anisotropy of bone--into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of mixed wave modes along an arbitrary direction in anisotropic porous media called quasi-waves. It was found that differences between phase and group velocities are due to the anisotropy of the bone microarchitecture, and that the experimental wave velocities are more accurately predicted by the poroelastic model when the fabric tensor variable is taken into account. This poroelastic wave propagation theory represents an alternative for bone quality assessment beyond BMD.     

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).     

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.     

Application of an effective medium theory for modeling ultrasound wave propagation in healing long bones

Quantitative ultrasound has recently drawn significant interest in the monitoring of the bone healing process. Several research groups have studied ultrasound propagation in healing bones numerically, assuming callus to be a homogeneous and isotropic medium, thus neglecting the multiple scattering phenomena that occur due to the porous nature of callus. In this study, we model ultrasound wave propagation in healing long bones using an iterative effective medium approximation (IEMA), which has been shown to be significantly accurate for highly concentrated elastic mixtures. First, the effectiveness of IEMA in bone characterization is examined: (a) by comparing the theoretical phase velocities with experimental measurements in cancellous bone mimicking phantoms, and (b) by simulating wave propagation in complex healing bone geometries by using IEMA. The original material properties of cortical bone and callus were derived using serial scanning acoustic microscopy (SAM) images from previous animal studies. Guided wave analysis is performed for different healing stages and the results clearly indicate that IEMA predictions could provide supplementary information for bone assessment during the healing process. This methodology could potentially be applied in numerical studies dealing with wave propagation in composite media such as healing or osteoporotic bones in order to reduce the simulation time and simplify the study of complicated geometries with a significant porous nature.     

Ultrasound-modulated light tomography assessment of osteoporosis

We present a preliminary series of clinical experiments showing that ultrasound modulation of light in tissues allows tissue properties to be determined well inside the tissue. In this series of clinical experiments the optical scattering coefficient determined by the optical technique is compared with the bone density obtained by dual x-ray absorption. A correlation of 0.84 (p = 0.005) was found for a limited number of patients, showing the potential of this technique for the assessment of osteoporosis.     

Numerical simulation of the dependence of quantitative ultrasonic parameters on trabecular bone microarchitecture and elastic constants

Finite-difference numerical simulation of ultrasound propagation in complex media such as cancellous bone represents a fertile alternative to analytical approaches because it can manage the complex 3D bone structure by coupling the numerical computation with 3D numerical models of bone microarchitecture obtained from high-resolution imaging modalities. The objective of this work was to assess in silico the sensitivity of ultrasound parameters to controlled changes of microarchitecture and variation of elastic constants. The simulation software uses a finite-difference approach based on the Virieux numerical scheme. An incident plane wave was propagated through a volume of bone of approximately 5 x 5 x 8 mm(3). The volumes were reconstructed from high-resolution micro-computed tomography data. An iterative numerical scenario of "virtual osteoporosis" was implemented using a dedicated image processing algorithm in order to modify the initial 3D microstructures. Numerical computations of wave propagation were performed at each step of the process. The sensitivity to bone material properties was also tested by changing the elastic constants of bone tissue. Our results suggest that ultrasonic variables (slope of the frequency-dependent attenuation coefficient and speed of sound) are mostly influenced by bone volume fraction. However, material properties and structure also appear to play a role. The impact of modifications of the stiffness coefficients remained lower than the variability caused by structural variations. This study emphasizes the potential of numerical computations tools coupled to realistic 3D structures to elucidate the physical mechanisms of interaction between ultrasound and bone structure and to assess the sensitivity of ultrasound variables to different bone properties.     

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).     

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.     

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。     

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.     

Ultrasonic non-destructive measurements of cortical bone thickness in human cadaver femur

The knowledge of the cortical bone thickness profile in human bone has a two-fold clinical significance: to study the stress occurring in a loaded bone structure to optimize the design of prostheses; and to predict the onset of advanced bone disease such as osteoporosis. In this study, the cortical bone thickness in three embalmed human cadaver femora were measured non-destructively using an ultrasonic technique. These thickness measurements were also made using a computed tomographic (CT) scanning method. Subsequently bones were sectioned and the actual bone thicknesses in the same regions were measured using a micrometer. The correlation coefficient between the actual thickness and the ultrasonically measured thickness was 0.95 and with the CT was 0.62. Thus, these results show that, under present experimental conditions, ultrasonic thickness measurements compare well with the micrometer actual thickness results. This technique, when fully developed, can be used as a non-destructive tool for quantitative cortical bone thickness measurements. Moreover, the ultrasonic technique does not use ionizing radiation.