Ultrasonic backscatter from flowing whole blood. II: Dependence on frequency and fibrinogen concentration

Earlier studies showed that ultrasonic backscatter from erythrocytes suspended in saline is a function of hematocrit and frequency and that it can be affected by flow disturbance. The experimental data agree well with the theories. Recently, studies have been extended to flowing whole blood. The results indicated that ultrasonic backscatter from flowing whole blood differs from that from saline suspensions of erythrocytes in that it is shear-rate dependent and species dependent. In the present article, data on the dependence of ultrasonic backscatter from flowing whole blood on frequency and on fibrinogen concentration are reported. It was found that ultrasonic backscatter from flowing whole blood also depends on fibrinogen concentration when red blood cell (RBC) aggregation exists. Moreover, when the blood is under conditions that favor RBC aggregation such as low shear rates, high fibrinogen concentration, or high hematocrits, Rayleigh scattering apparently is no longer sufficient to describe its scattering behavior.     

Acoustic characterization in whole blood and plasma of site-targeted nanoparticle ultrasound contrast agent for molecular imaging

The ability to enhance specific molecular markers of pathology with ultrasound has been previously demonstrated by our group employing a nanoparticle contrast agent [Lanza et al., Invest. Radiol. 35, 227-234 (2000); Ultrasound Med. Biol. 23, 863-870 (1997)]. One of the advantages of this agent is very low echogenicity in the blood pool that allows increased contrast between the blood pool and the bound, site-targeted agent. We measured acoustic backscatter and attenuation coefficient as a function of the contrast agent concentration, ambient pressure, peak acoustic pressure, and as an effect of duty cycle and wave form shape. Measurements were performed while the nanoparticles were suspended in either whole porcine blood or plasma. The nanoparticles were only detectable when insonified within plasma devoid of red blood cells and were shown to exhibit backscatter levels more than 30 dB below the backscatter from whole blood. Attenuation of nanoparticles in whole porcine blood was not measurably different from that of whole blood alone over a range of concentrations up to eight times the maximum in vivo dose. The resulting data provide upper bounds on blood pool attenuation coefficient and backscatter and will be needed to more precisely define levels of molecular contrast enhancement that may be obtained in vivo.     

表面粗糙度对固体内部超声背散射的影响

超声背散射法可通过多晶体金属内部的空间方差信号,实现微观结构参数的无损评价,但表面粗糙度对评价模型的精度及实用性存在显著影响.基于高斯声束理论推导垂直入射粗糙界面的纵波声场,以此研究声能的Wigner分布规律;在超声的波长远大于粗糙度的前提下,构造表面粗糙度修正系数,并建立粗糙界面的单次散射响应模型,揭示粗糙度对超声波背向散射的影响规律.用304不锈钢制备轮廓均方根值为0.159μm的光滑试块和25.722μm的粗糙试块开展超声背散射实验,结果表明模型在粗糙度修正前后均可实现光滑试块的晶粒尺寸有效评价,但未经修正的传统模型对粗糙试块的晶粒尺寸评价结果与金相法结果的相对误差高达-21.35%,而本模型的评价结果与金相法结果符合得很好,相对误差仅为1.35%.可见,本模型能有效补偿粗糙度引起的超声背散射信号衰减,从而提高晶粒尺寸无损评价的精度.     

骨小梁材料特性对超声背散射信号的影响

基于时域有限差分法(FDTD)建立了松质骨的超声背散射仿真系统,研究了骨小梁材料特性对超声背散射信号的影响。首次得到松质骨中的超声背散射系数(BSC)和积分背散射系数(IBC)随骨小梁材料参数(密度、拉梅常数、黏度系数及声阻抗系数)的变化关系。研究结果表明,IBC随骨小梁密度的增加而增加;BSC和IBC随拉梅常数的增加而增加、随第一黏度系数的增加而近似线性地减小,第二黏度的变化对背散射信号的影响很小;背散射参数随阻抗系数的增加而减小。说明松质骨中的超声背散射特性不仅受骨矿密度(BMD)和骨微结构的影响,还与骨小梁的材料参数密切相关。研究结果有利于理解松质骨中超声的背散射特性,对松质骨骨质状况的评价有一定帮助。      

The extracellular matrix is an important source of ultrasound backscatter from myocardium

Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10-30 microm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from 15.4 +/- 0.8 to 12.6 +/- 1.1dB for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.     

Errors in ultrasonic scatterer size estimates due to phase and amplitude aberration

Current ultrasonic scatterer size estimation methods assume that acoustic propagation is free of distortion due to large-scale variations in medium attenuation and sound speed. However, it has been demonstrated that under certain conditions in medical applications, medium inhomogeneities can cause significant field aberrations that lead to B-mode image artifacts. These same aberrations may be responsible for errors in size estimates and parametric images of scatterer size. This work derives theoretical expressions for the error in backscatter coefficient and size estimates as a function of statistical parameters that quantify phase and amplitude aberration, assuming a Gaussian spatial autocorrelation function. Results exhibit agreement with simulations for the limited region of parameter space considered. For large values of aberration decorrelation lengths relative to aberration standard deviations, phase aberration errors appear to be minimal, while amplitude aberration errors remain significant. Implications of the results for accurate backscatter and size estimation are discussed. In particular, backscatter filters are suggested as a method for error correction. Limitations of the theory are also addressed. The approach, approximations, and assumptions used in the derivation are most appropriate when the aberrating structures are relatively large, and the region containing the inhomogeneities is offset from the insonifying transducer.     

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dBcmMHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).     

骨小梁中超声背散射信号的频率分析及其微结构的估计

骨质疏松症是一种骨强度下降的全身性骨骼疾病,骨强度的下降是骨量减少和骨微结构退化的共同结果。相比于传统的超声透射方法,超声背散射法可提供更多的骨微结构信息,而对于松质骨结构的建模能有助于结构信息的获取。本文将骨小梁简化为单圆柱模型(圆柱状的单根骨小梁浸于骨髓中),并基于此模型对超声背散射与频率的关系进行分析。用铝线代替骨小梁做仿体实验,通过实验与理论结果的比较来验证单圆柱模型的可行性。     

Ultrasonic visualization of dynamic behavior of red blood cells in flowing blood

It is well known that the scatter of ultrasound by blood is mainly attributed to red blood cells (RBCs) and RBC aggregation. In the present review, researches of hemodynamic influence on RBC aggregation and ultrasound backscatter from blood were overviewed. A mock flow loop and a cylindrical chamber were employed to produce various blood flows, such as pulsatile, oscillatory, and rotational flow. The “black hole” (BLH), a dark hole at the tube center surrounded by bright zone in the cross sectional B-mode image and “bright collapsing ring” (BRCR) phenomena, appearance of bright ring at the periphery and collapse of it at the center during a pulsatile cycle, were observed under pulsatile flow. The combined effects of shear rate and flow acceleration on RBC aggregation were suggested as a possible mechanism for these phenomena. The stroke volume-dependence of the “bright ring” phenomenon under oscillatory flow could also be explained by flow acceleration. The enveloped echo images from rotational flow in a compact blood chamber showed the spatial and temporal variations of RBC aggregation, which varied with the mammalian species. In the stenotic model, it was found that the echogenic variation increased locally at a distance of three tube diameters downstream from the stenosis during decelerating period, which was proposed to be mainly due to flow turbulence. The similar ‘bright ring’ was also observed fromin vivo human carotid artery in harmonic imaging.     

Tests of the accuracy of a data reduction method for determination of acoustic backscatter coefficients

The accuracy of a new method for measuring ultrasonic backscatter coefficients was tested, using narrow-band pulses and well-defined media having scatterers randomly distributed in space. Experimentally determined values agree very well with theoretical values for wide ranges of experimental parameters, these ranges being applicable in measurements made on human soft tissues. An important outcome is that the method yields accurate results for scattering media positioned anywhere from the nearfield through the farfield of the nonfocused transducers employed. In addition, backscatter coefficients can be determined for a broad range of gate durations.     

超声表观积分背散射系数评价新生儿骨状况的可行性研究

新生儿骨发育状况的超声评价有重要意义。本文研究用超声背散射信号来评价新生儿骨发育状况的可行性。提出将超声表观积分背散射系数(AIB)用于评价新生儿松质骨状况,研究了不同超声频率下AIB与婴儿体重、出生天数之间的关系。研究结果表明,足月儿的AIB明显大于早产儿的AIB;足月儿的体重和AIB相关性较弱;早产儿的AIB参数和出生天数具有较高的正相关性(R=0.633)。说明超声背散射信号及其参数AIB可用于评价新生儿松质骨发育状况。      

Estimating concentration of ultrasound contrast agents with backscatter coefficients: experimental and theoretical aspects

Ultrasound contrast agents (UCAs) have been explored as a means to enhance therapeutic techniques. Because the effectiveness of these techniques relies on the UCA concentration at a target site, it would be beneficial to estimate UCA concentration noninvasively. In this study, a noninvasive method for estimating UCA concentration was developed in vitro. Backscatter coefficients (BSCs) estimated from measurements of Definity(?) UCAs were fitted to a theoretical scattering model in the 15-25 MHz range using a Levenberg-Marquardt regression technique. The model was defined by the UCA size distribution and concentration, and therefore concentration estimates were extracted directly from the fit. Calculation of the BSC was accomplished using planar reference measurements from the back wall of a Plexiglas(?) chamber and an average of 500 snapshots of ultrasonic backscatter from UCAs flowing through the chamber. In order to verify the ultrasonically derived UCA concentration estimates, a sample of the UCAs was extracted from the flow path and the concentration was estimated with a hemacytometer. UCA concentrations of 1, 2, and 5 times the dose recommended by the manufacturer were used in experiments. All BSC-based estimates were within one standard deviation of hemacytometer based estimates for peak rarefactional pressures of 100-400 kPa.     

Effect of trabecular bone material properties on ultrasonic backscattering signals

In this study, ultrasonic backscattering signals in cancellous bones were obtained by finite difference time domain （FDTD） simulations, and the effect of trabecular material properties on these signals was analyzed. The backscatter coefficient （BSC） and integrated backscatter coefficient （IBC） were numerically investigated for varying trabecular bone material properties, including density, Lame coefficients, viscosities, and resistance coefficients. The results show that the BSC is a complex function of trabecular bone density, and the IBC increases as density increases. The BSC and IBC increase with the first and second Lame coefficients. While not very sensitive to the second viscosity of the trabeculae, the BSC and IBC decrease as the first viscosity and resistance coefficients increase. The results demonstrate that, in addition to bone mineral density （BMD） and microarchitecture, trabecular material properties significantly influence ultrasonic backseattering signals in cancellous bones. This research furthers the understanding of ultrasonic backscattering in cancellous bones and the characterization of cancellous bone status.     

Fundamental precision limitations for measurements of frequency dependence of backscatter: applications in tissue-mimicking phantoms and trabecular bone.

Various models for ultrasonic scattering from trabecular bone have been proposed. They may be evaluated to a certain extent by comparison with experimental measurements. In order to appreciate limitations of these comparisons, it is important to understand measurement precision. In this article, an approach proposed by Lizzi and co-workers is adapted to model precision of estimates of frequency-dependent backscatter for scattering targets (such as trabecular bone) that contain many scatterers per resolution cell. This approach predicts uncertainties in backscatter due to the random nature of the interference of echoes from individual scatterers as they are summed at the receiver. The model is validated in experiments on a soft-tissue-mimicking phantom and on 24 human calcaneus samples interrogated in vitro. It is found that while random interference effects only partially explain measured variations in the magnitude of backscatter, they are virtually entirely responsible for observed variations in the frequency dependence (exponent of a power law fit) of backscatter.     

Spectral estimation for characterization of acoustic aberration

Spectral estimation based on acoustic backscatter from a motionless stochastic medium is described for characterization of aberration in ultrasonic imaging. The underlying assumptions for the estimation are: The correlation length of the medium is short compared to the length of the transmitted acoustic pulse, an isoplanatic region of sufficient size exists around the focal point, and the backscatter can be modeled as an ergodic stochastic process. The motivation for this work is ultrasonic imaging with aberration correction. Measurements were performed using a two-dimensional array system with 80 x 80 transducer elements and an element pitch of 0.6 mm. The f number for the measurements was 1.2 and the center frequency was 3.0 MHz with a 53% bandwidth. Relative phase of aberration was extracted from estimated cross spectra using a robust least-mean-square-error method based on an orthogonal expansion of the phase differences of neighboring wave forms as a function of frequency. Estimates of cross-spectrum phase from measurements of random scattering through a tissue-mimicking aberrator have confidence bands approximately +/- 5 degrees wide. Both phase and magnitude are in good agreement with a reference characterization obtained from a point scatterer.     

Influence of the precision of spectral backscatter measurements on the estimation of scatterers size in cancellous bone

The goal of this study is to propose a model for the ultrasonic frequency-dependent backscatter coefficient in femoral cancellous bone. This model has been developed with success to predict backscatter in human calcaneal bone [Jenson, Ultr. Med. Biol. 2003]. A weak scattering model is used and the backscatter coefficient is expressed in terms of a Gaussian autocorrelation function of the medium. The backscatter coefficient is computed and comparison is made with experimental data for 37 specimens and for frequency ranging from 0.4 to 1.2 MHz. An excellent agreement between experimental data and predictions is found for both the magnitude and the frequency-dependence of the backscatter coefficient. Then, a nonlinear regression is performed for each specimen, and the mean trabecular thickness is estimated. Experimental data and theoretical predictions are averaged over the 37 specimens. We also find a close agreement between theoretical predictions obtained using the Gaussian autocorrelation function (scatterer size=134+/-15 microm) and the mean trabecular thickness (Tb.Th=132+/-12 microm) derived from the analysis of bone 3-D micro-architecture using high-resolution micro-tomography. However, the correlation between individual experimental and estimated Tb.Th values is moderate (R(2)=0.44). The performance of the estimator are limited mainly by two factors: interference noise due to random positioning of the scatterers and attenuation. We show that the fundamental limitation of our estimator due to the speckle noise is around 5 microm for trabecular thickness estimation. This limitation is lower than the observed biological variability which is around 30 microm and should not be a limiting factor for individual prediction. A second limitation is the tremendous attenuation encountered in highly scattering media such as cancellous bone, which results in highly damped backscatter signals. The compensation for attenuation is difficult to perform, and it may be a critical point that limits the precision of the estimator.     

Modification of Spalart-Allmaras model with consideration of turbulence energy backscatter using velocity helicity

The correlation between the velocity helicity and the energy backscatter is proved in a DNS case of 256³-grid homogeneous isotropic decaying turbulence. The helicity is then proposed to be employed to improve turbulence models and SGS models. Then Spalart-Allmaras turbulence model (SA) is modified with the helicity to take account of the energy backscatter, which is significant in the region of corner separation in compressors. By comparing the numerical results with experiments, it can be concluded that the modification for SA model with helicity can appropriately represent the energy backscatter, and greatly improves the predictive accuracy for simulating the corner separation flow in compressors.     

Contraction-related variation in frequency dependence of acoustic properties of canine myocardium

Results of experiments performed in several laboratories indicate that contracting myocardium exhibits a cyclic variation of the magnitude of ultrasonic backscatter, with maxima occurring at end-diastole and minima at end-systole. The mechanisms responsible for this variation are not well understood. The purpose of the present study was to determine whether the frequency dependence of backscatter exhibits systematic variation throughout the cardiac cycle, analysis of which may facilitate improved understanding of biologic factors responsible for the cyclic variation of the magnitude of backscatter. In this study, the myocardial backscatter coefficient, as a function of frequency, was measured throughout the cardiac cycle in nine open-chest dogs. The frequency dependence of the backscatter coefficient was computed from a least-squares linear fit to log backscatter coefficient versus log frequency data. A cyclic variation of frequency dependence of backscatter was found with maximum near end-diastole (f2.6 +/- 0.1) and minimum near end-systole (f2.2 +/- 0.1), a significant variation (p less than 0.01). These results suggest that mechanisms responsible for the cyclic variation of backscatter may include changes in the effective size of the dominant scatterers throughout the cardiac cycle. An alternative explanation for the observed variation is an increase in the myocardial attenuation coefficient during systole followed by a decrease in diastole.     

Rheo-acoustical study of the shear disruption of reversible aggregates. Ultrasound scattering from concentrated suspensions of red cell aggregates

Shear-induced disruption of reversible aggregates or clusters in a concentrated suspension is investigated by ultrasound backscattering in the low shear regime. Fractal aggregates are considered as non-Brownian scatterers much smaller than the wavelength with acoustic properties close to those of the surrounding liquid, so that the attenuation of the coherent field is weak and multiple scattering can be neglected. The concept of variance in local particle volume fraction is used to deduce a first-order expression of the ultrasound scattering cross section per unit volume for Rayleigh scatterers in a dense suspension. On the basis of a scaling law for the shear-induced disruption of aggregates, the shear stress dependence of the ultrasonic scattered intensity from a dense suspension of clusters is derived. In a second part, the shear breakup of hardened red blood cell aggregates is investigated in plane-plane flow geometry by ultrasound scattering. Rheo-acoustical experiments are analyzed within the framework of the self-consistent field approximation and the scaling laws currently used in microrheological models. Finally, the ability of ultrasonic, light reflectometry and viscometry methods to provide quantitative information about red blood cell aggregation and membrane adhesiveness is discussed.