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.     

核磁共振骨皮质成像关键技术研究进展

骨质量尤其是骨皮质质量的评价方法对骨病的诊断和治疗有重要意义. 随着社会快速老龄化, 如何非侵入地获得准确实用的骨质量评价指标已成为医学物理领域亟待解决的热点问题. 目前有多种骨质量评价方法, 其中双能X射线吸收法获得的骨矿密度值是评价骨质量的现行金标准, 但这个参数有明显缺陷, 如不能反映骨皮质中的有机基质、微结构、孔隙度及灌注等情况, 所以不能准确诊断骨质疏松和预测骨折等疾病. 由于骨的磁共振信号衰减极快,所以常规磁共振成像技术不能探测到骨的信号. 近年来随着理论、方法和设备的不断进步, 超短回波磁共振骨成像成为可能. 本文简要介绍超短回波磁共振骨成像的基础物理理论, 结合作者所在实验室的研究工作对各类定性及定量超短回波磁共振骨皮质成像新方法进行综述, 总结各类方法的特点、适用范围及不足, 指出进一步研究的方向、重点及步骤, 对超短回波磁共振成像在骨质量评估方面的理论研究及工程应用具有指导意义. 关键词： 超短回波 核磁共振成像 骨矿物密度 骨皮质     

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。     

Element analysis in femur of diabetic osteoporosis model by SRXRF microprobe

Diabetes mellitus affects bone metabolism and leads to osteopenia and osteoporosis, but its pathogenic mechanism remains unknown. To address this problem, mineral element of bone was analyzed in experimental diabetic osteoporosis model. Male Wistar rats were randomly divided into streptozotocin (STZ)-induced diabetic group (n=5) and control group (n=5). The experiment lasted 68 days and at the end of the experiment, femoral bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry and element content in femur of animals was determined by synchrotron radiation X-ray fluorescence (SRXRF) microprobe analysis technique. Results showed that femoral BMD in diabetic group was significantly lower than that in control (P<0.01). Relative mineral content of calcium (Ca), phosphorus (P) and zinc (Zn) in diabetic femurs decreased significantly compared to controls. And strontium (Sr) in diabetics reduced 11% (P=0.09). Relative content of sulfur (S) in average was statistically higher (P<0.01) in diabetics than that in controls. But no obvious difference was observed in relative content of chromium (Cr), iron (Fe), copper (Cu), and lead (Pb) between the two groups. Statistical analysis revealed that Ca correlated positively with P (R=0.85 and P<0.001), with Sr (R=0.38 and P<0.05) and with Zn (R=0.37 and P<0.05). Whereas, Zn correlated negatively with S (R=-0.40 and P<0.05). Our results reveal that loss of minerals accounts for the BMD reduction in diabetics.     

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.     

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.     

Nonlinear inversion of ultrasonic guided waves for in vivo evaluation of cortical bone properties

Ultrasonic guided waves (UGWs), which propagate throughout the entire thickness of cortical bone, are attractive for the early diagnosis of osteoporosis. However, this is challenging due to the impact of soft tissue and the inherent difficulties related to multiparametric inversion of cortical bone quality factors, such as cortical thickness and bulk wave velocity. Therefore, in this research, a UGW-based multi-parameter inversion algorithm is developed to predict strength-related factors. In simulation, a free plate (cortical bone) and a bilayer plate (soft tissue and cortical bone) are used to validate the proposed method. The inversed cortical thickness (CTh), longitudinal velocity (V_L) and transverse velocity (V_T) are in accordance with the true values. Then four bovine cortical bone plates were used in in vitro experiments. Compared with the reference values, the relative errors for cortical thickness were 3.96%, 0.83%, 2.87%, and 4.25%, respectively. In the in vivo measurements, UGWs are collected from the tibias of 10 volunteers. The theoretical dispersion curves depicted by the estimated parameters (V_T, V_L, CTh) match well with the extracted experimental ones. In comparison with dual-energy x-ray absorptiometry, our results show that the estimated transverse velocity and cortical thickness are highly sensitive to osteoporosis. Therefore, these two parameters (CTh and V_T) of long bones have potential to be used for diagnosis of bone status in clinical applications.     

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.     

X-ray imaging characterization of femoral bones in aging mice with osteopetrotic disorder

Aging mice with a rare osteopetrotic disorder in which the entire space of femoral bones are filled with trabecular bones are used as our research platform. A complete study is conducted with a micro computed tomography (CT) system to characterize the bone abnormality. Technical assessment of femoral bones includes geometric structure, biomechanical strength, bone mineral density (BMD), and bone mineral content (BMC). Normal aging mice of similar ages are included for comparisons. In our imaging work, we model the trabecular bone as a cylindrical rod and new quantitative which are not previously discussed are developed for advanced analysis, including trabecular segment length, trabecular segment radius, connecting node number, and distribution of trabecular segment radius. We then identified a geometric characteristic in which there are local maximums (0.0049, 0.0119, and 0.0147 mm) in the structure of trabecular segment radius. Our calculations show 343% higher in percent trabecular bone volume at distal-metaphysis; 38% higher in cortical thickness at mid-diaphysis; 11% higher in cortical cross-sectional moment of inertia at mid-diaphysis; 42% higher in cortical thickness at femur neck; 26% higher in cortical cross-sectional moment of inertia at femur neck; 31% and 395% higher in trabecular BMD and BMC at distal-metaphysis; 17% and 27% higher in cortical BMD and BMC at distal-metaphysis; 9% and 53% higher in cortical BMD and BMC at mid-diaphysis; 25% and 64% higher in cortical BMD and BMC at femur neck. Our new quantitative parameters and findings may be extended to evaluate the treatment response for other similar bone disorders.     

一种基于Windows界面的正电子湮没谱分析软件包

在保留正电子寿命谱分析程序PATFIT和连续谱分析程序MELT主要优点的基础上研究开发了一个新的正电子湮没谱分析软件PASA。主要的改进包括:将PATFIT、MELT和多普勒展宽谱3种正电子湮没分析方法集成在Windows界面程序中, MELT程序脱离MATLAB环境独立运行; 编写了完整的多普勒展宽谱分析程序, 谱文件的读取、输入参数的调节和拟合结果的输出更加方便快捷, 重点加强了正电子湮没实验谱和拟合结果的图形显示、介绍PASA软件的使用经验。Based on the commonly used PATFIT and MELT program, a new program package — Positron Annihilation Spectrum Analysis(PASA) with many user\|friendly applications was developed. The main modifications are: three kinds of positron analysis methods (PATFIT, MELT, Doppler) were incorporated into PASA; MELT could run independently without being in MATLAB environment; Detailed Doppler analysis program were programmed into PASA. Experiences of using the PASA program were also introduced.     

Study on the mean trabecular bone spacing based on fundamental frequency estimation method

Ultrasonic backscatter signals from the cancellous bone can be used to diagnose osteoporosis effectively due to its ability to provide the information of bone microstructure. Mean trabecular bone spacing(MTBS)is one of the important parameters for characterization of bone microstructure.This paper proposed a MTBS estimating method based on the fundamental frequency estimation,which was applied to backscatter signals from simulations, and in vitro bovine trabeculae.The estimated MTBS were compared with those of simplified inverse filter tracking(SIFT)algorithm and autoregressive(AR)cepstrum method.The results demonstrated that the proposed method is very robust for the MTBS estimation with more precise estimates and smaller estimated variance in the presence of a small signal-to-noise ratio (SNR),and a large scattering strength ratio of diffuse scatterers to regular ones.     

核磁共振技术测量生物骨密度的设备及方法

诊断骨质疏松症多采用双能X射线吸收方法测得的骨密度数据作为依据,但是该方法存在一定量的辐射,且准确性不高.该文设计并改进了一套核磁共振装置,通过在发射和接收线圈之间增加快速切换开关(Q-switch),使得核磁共振自旋回波的回波时间缩短至80μs的超短回波时间范围,实现了对T_2弛豫时间很短的骨组织核磁共振自旋回波信号的采集;将T_2弛豫时间谱和双能X射线方法测量的骨密度数据进行了对比研究,发现核磁共振T_2弛豫时间谱上300~500μs之间的峰值与骨密度之间具有良好的线性关系,随着骨密度的增大,相应的T_2弛豫时间峰值缩短;利用核磁共振T_2弛豫时间谱技术,结合双能X射线吸收方法,提出了一种测量生物离体骨骼样本骨密度的方法.该测量方案具有测量速度快、对人体完全无害、跨时期比较性强等优点,很好的弥补了现有测量方法的不足,在骨质疏松症的诊断和疗效评估中有着良好的应用前景.     

采用超声导波特征参量的骨质疏松识别方法

骨质的定期检测对骨质疏松的防治至关重要。本文研究了骨质疏松对超声导波在人体长骨中传播的影响。提出采用多尺度小波变换方法对接收到的导波信号进行处理,通过分析在不同传播距离下高阶小波细节分量所占信号总能量的变化,来判断是否患有骨质疏松症。在13位志愿者的小腿胫骨上进行超声测量,得到导波信号。经多尺度小波变换方法的分析处理结果显示在13位志愿者中,有7位志愿者的超声导波信号随着传播距离的改变,其主要频率成分发生了明显的变化,显示这7位志愿者患有骨质疏松症。这一诊断结果与X射线技术诊断结果相比,准确率可以达到92.3%,表明本文所提出的利用小波多尺度变换方法对长骨进行超声诊断具有较好的潜力。      

Diagnosis of osteoporosis based on multi-scale wavelet parameters of ultrasonic guided waves

Evaluating bone regularly is important to prevent and control the disease of osteoporosis. Impact of osteoporosis on ultrasonic guided waves propagating in human long bones is studied in this paper. Multi-scale wavelet transform is proposed to process the received guided waves, and by analyzing energy changes in detail components of high order wavelet at different propagating distance to assess if osteoporosis happened. The guided waves signals are collected from the tibias of 13 volunteers. Based on the analysis of multi-scale wavelet transform, the high order detail components d6 and d5 changed dramatically with the propagation of ultrasonic guided waves along long bones, which means these 7 volunteers are diagnosed with osteoporosis. Compared with X-ray diagnosis, the effectiveness of this method can reach 92.3% in 13 volunteers. This suggests the multi-scale wavelet transform method is potential in ultrasonic assessment of bone quality.     

Distribution of longitudinal wave properties in bovine cortical bone in vitro

The detailed spatial distributions of longitudinal ultrasonic velocity in cortical bone specimens obtained from three bovine femoral diaphysis were experimentally investigated using a pulse-echo system. The relationship between velocity, density, bone mineral density (BMD) and microstructure was investigated. Velocity was found to vary as a function of the direction of propagation and the location of the measured specimens in the bone diaphysis. A significant correlation was found between density and velocity, and between density and BMD. In some parts with plexiform structure, clear variations in velocity anisotropy were found despite no significant difference in density, BMD and microstructure.     

Application of the dual-frequency ultrasonometer for osteoporosis detection

The paper presents results of a clinical validation study of Bone UltraSonic Scanner (BUSS), a novel dual-frequency axial transmission ultrasonometer, developed by Artann Laboratories. Assessment of bone conditions is based on evaluating relative changes of the axial profiles of ultrasonic characteristics in long bones and utilizes bulk and guided acoustic waves. The objective of this study was to determine the ability of BUSS to discriminate osteoporosis development stages. A total of 93 menopausal and post-menopausal women divided into five groups from normal to advanced osteoporosis according to their DXA hip t-score were enrolled in the study. The 2D waveform profiles at low (0.1 MHz) and high (1 MHz) frequencies were obtained by scanning 15 cm along the proximal tibia.A multi-parametric linear classifier based on a set of the parameters derived from 2D acoustic waveform profiles has been developed. The efficiency of this classifier in differentiating osteoporosis from a normal sample was assessed using a receiver operating characteristic (ROC) curve analysis. Based on the ROC analysis, BUSS demonstrated 76% sensitivity and 70% specificity to DXA-identified osteoporosis. The area under the ROC curve, which is a measure of how well a parameter can distinguish between the two diagnostic groups (diseased/normal) was 79.3%. The study confirmed BUSS’s capability to discriminate between stages of bone atrophy and in particular to distinguish early changes induced by osteoporosis.     

Proton magnetic relaxation in bone marrow related to age and bone mineral density: low-resolution in vitro studies.

Detailed analysis of proton spin-spin and spin-lattice relaxation behaviors of the bone marrow in the presence of trabecular bone network was performed at low-resolution (B(0) = 0.496T) on rat vertebrae specimens deprived of spinal cord. Two groups of samples, from young and old healthy animals, were investigated before cellular necrosis had started. BMD measurements were carried out to quantify the expected age-related modifications of the trabecular bone network. 1H-MR measurements were also performed on the same samples, deprived of marrow and saturated with water, in order to control the validity of a possible interpretation of the marrow 1H-MR characteristics, in terms of marrow components, and to investigate the possible employment of these samples to study the trabecular bone network properties. We pointed out that: 1) a bimodal distribution of T(2i) and T(1i) values (distinguishing "fast" and "slow" relaxations) describes satisfactorily all the 1H-MR experimental decays; 2) age-related modifications of the trabecular bone network are marked by correlate variations of the BMD value and of the proton spin-spin relaxation rates in water saturated samples; 3) age-related modifications of marrow are underlined by variations of the average value of the "fast" T(2i) and of the "slow" T(1i) relaxation time distributions, which could be attributed to the marrow components different from the fat granules of the adipose cells.Our results suggest that studies in vitro on bone tissue, by 1H-MR techniques at low-resolution, may contribute to a better bone function characterization and, therefore, to a better clinical utilization of MRI techniques.     

超声轴向传播技术评价长骨的研究

用超声轴向传播技术评价长骨状况已成为近年来的一个研究热点。本文首先介绍了第一到达波(FAS)法、超声Lamb波及柱面导波法在评价长骨皮质骨状况方面的研究进展,最后分析和讨论了当前研究中存在的问题及应该研究的方向。     

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.     

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.