Boundary element simulation of backscattering properties for red blood with high frequency ultrasonic transducers

High frequency ultrasonic imaging (e.g. >30 MHz) from blood is difficult due to its tenuous backscattered pressure and the interference from adjacent tissues as well. To increase the sensitivity focused transducer has to be used, thus raising the complexity of interpreting the received signals. A numerical simulation of the ultrasonic scattering property from erythrocyte and rouleaux based on boundary element method was performed with experimental results based on a modified substitution method. The results (proportional relationship between backscattered pressure and frequency and the frequency limit for Rayleigh scattering) closely coincide with experimental data for erythrocyte. Rouleaux model results also show the dependence of degree of red cell aggregation on backscattering properties. The boundary element method serves as a good means to calculate the acoustic scattering from blood cells under arbitrary incident waves.     

High-frequency ultrasound backscattering by blood: analytical and semianalytical models of the erythrocyte cross section

This paper proposes analytical and semianalytical models of the ultrasonic backscattering cross section (BCS) of various geometrical shapes mimicking a red blood cell (RBC) for frequencies varying from 0 to 90 MHz. By assuming the first-order Born approximation and by modeling the shape of a RBC by a realistic biconcave volume, different scattering behaviors were identified for increasing frequencies. For frequencies below 18 MHz, a RBC can be considered a Rayleigh scatterer. For frequencies less than 39 MHz, the general concept of acoustic inertia tensor is introduced to describe the variation of the BCS with the frequency and the incidence direction. For frequencies below 90 MHz, ultrasound backscattering by a RBC is equivalent to backscattering by a cylinder of height 2 microm and diameter 7.8 microm. These results lay the basis of ultrasonic characterization of RBC aggregation by proposing a method that distinguishes the contribution of the individual RBC acoustical characteristics from collective effects, on the global blood backscattering coefficient. A new method of data reduction that models the frequency dependence of the ultrasonic BCS of micron-sized weak scatterers is also proposed. Applications of this method are in tissue characterization as well as in hematology.     

Analysis of microstructural alterations of normal and pathological breast tissue in vivo using the AR cepstrum

The mean scatterer spacing is considered to be an important parameter for describing ultrasonic scattering and characterization of biological tissue. Autoregressive models are widely used in parametric techniques for spectral estimation. In this paper, we describe the results of a careful examination of the mean scatterer spacing parameter in normal and pathological breast tissues in vivo using the autoregressive cepstrum. Our experimental results carried out at 4.5 MHz using weakly focused pulse-echo single element transducer show that the mean scatterer spacing in normal breast tissues in vivo is 1.25+/-0.21 mm whereas in several pathological breast tissues, it is between 0.82+/-0.10 and 1.09+/-0.07 mm. These results indicate good correlation with microstructure of breast tissue characterization, and hence the AR cepstrum holds promise that it could be used as an effective method for signal analysis of ultrasonic scattering and characterization of breast tissues scatterers.     

Ultrasonic backscatter from mammalian tissues

Ultrasonic B-mode images are formed from echoes backscattered from tissue structures in the body. Quantitative analysis of this signal from tissues may provide additional information about the tissues which may be valuable for clinical diagnosis. Results on measurements of backscatter properties of tissues such as heart, liver, and blood have been reported by a number of investigators. Data on other tissues such as spleen, kidney, and pancreas, however, are still very scanty. In this paper, results on ultrasonic backscattering properties of bovine heart, liver, kidney, spleen, pancreas, and rat myocardium, recently obtained in our laboratory utilizing a computerized system over the frequency range of 2-7 MHz, are presented. The results show that for all the tissues investigated, backscatter from liver is the highest, while that from spleen is the lowest. Liver and pancreas exhibit frequency dependence distinctively different from other tissues. Moreover, backscatter from bovine myocardium is found to be higher than that from rat myocardium. The significance of these findings in relation to the histological composition of these tissues is discussed.     

Ultrasonic attenuation and velocity properties in rat liver as a function of fat concentration: a study at 100 MHz using a scanning laser acoustic microscope

This study examines the extent to which ultrasonic attenuation coefficients and velocity properties change between normal and fatty rat liver. The view of this problem is toward the application in clinical medicine in the future. Fatty livers were produced in rats by feeding them alcohol diets in liquid form. The animals were sacrificed and the fat concentration of the liver specimens determined. The fat concentration varied from 2.5% to 16.8% wet weight. The ultrasonic attenuation coefficient and velocity properties in 28 specimens were measured at 100 MHz with the scanning laser acoustic microscope (SLAM). Regression analysis was applied to the liver's ultrasonic propagation properties as a function of fat concentration. The results show that the attenuation coefficient increases at a rate of 1.08 dB/mm/% fat and the velocity decreases at a rate of 2.3 m/s/% fat as the fat concentration increases.     

Enhancement of ultraweak photon emission with 3 MHz ultrasonic irradiation on transplanted tumor tissues of mice

We investigated photon emissions of various bio-samples which were induced by ultrasonic stimulation. It has been reported that ultrasonic stimulations induced the thermal excitation of the bio-tissues. After ultrasonic stimulation, any measurement of photon radiation in the visible spectral range has not been carried out yet. The instruments consisted of electronic devices for an ultrasonic generator of the frequency 3 MHz and a photomultiplier tube (PMT) system counting photons from bio-tissues. The transplanted tumor tissues of mice were prepared for the experiments and their liver and spleen tissues were also used for the controls. It was found that the continuous ultrasonic stimulations with the electrical power 2300 mW induced ultraweak photon emissions from the tumor tissues. The number of induced photon was dependent of the type of the tissues and the stimulation time intervals. The level of photon emission was increased from the mouse tumor exposed to the ultrasonic stimulations, and the changes were discriminated from those of the spleens and livers.     

Experimental ultrasound characterization of red blood cell aggregation using the structure factor size estimator

The frequency dependence of the ultrasonic backscattering coefficient (BSC) was studied to assess the level of red blood cell (RBC) aggregation. Three monoelement focused wideband transducers were used to insonify porcine blood sheared in a Couette flow from 9 to 30 MHz. A high shear rate was first applied to promote disaggregation. Different residual shear rates were then used to promote formation of RBC aggregates. The structure factor size estimator (SFSE), a second-order data reduction model based on the structure factor, was applied to the frequency-dependent BSC. Two parameters were extracted from the model to describe the level of aggregation at 6% and 40% hematocrits: W, the packing factor, and D the aggregate diameter, expressed in number of RBCs. Both parameters closely matched theoretical values for nonaggregated RBCs. W and D increased during aggregation with stabilized values modulated by the applied residual shear rate. Furthermore, parameter D during the kinetics of aggregation at 6% hematocrit under static conditions correlated with an optical RBC aggregate size estimation from microscopic images (r(2)=0.76). To conclude, the SFSE presents an interesting framework for tissue characterization of partially correlated dense tissues such as aggregated RBCs.     

In vitro chronic hepatic disease characterization with a multiparametric ultrasonic approach

Although, high resolution, real-time ultrasonic (US) imaging is routinely available, image interpretation is based on grey-level and texture and quantitative evaluation is limited. Other potentially useful diagnostic information from US echoes may include modifications in tissue acoustic parameters (speed, attenuation and backscattering) resulting from disease development. Changes in acoustical parameters can be detected using time-of-flight and spectral analysis techniques. The objective of this study is to explore the potential of three parameters together (attenuation coefficient, US speed and integrated backscatter coefficient-IBC) to discriminate healthy and fibrosis subgroups in liver tissue. Echoes from 21 fresh in vitro samples of human liver and from a plane reflector were obtained using a 20-MHz central frequency transducer (6-30 MHz bandpass). The scan plane was parallel to the reflector placed beneath the liver. A 30 x 20 matrix of A-scans was obtained, with a 200-microm step. The samples were classified according to the Metavir scale in five different degrees of fibrosis. US speed, attenuation and IBC were estimated from standard methods described in the literature. Statistical tests were applied to the results of each parameter individually and indicated that it was not possible to identify all the fibrosis groups. Then a discriminant analysis was performed for the three parameters together resulting in a reasonable separation of fibrotic groups. Although the number of tissue samples is limited, this study opens the possibility of enhancing the discriminant capability of ultrasonic parameters of liver tissue disease when they are combined together.     

空间频率域超声背散射参量用于骨质状况的评价*

在超声背散射骨质评价中,不同测量感兴趣区域(ROI)的超声背散射信号会有波动,致使诊断准确度降低。该文目的是研究超声背散射信号随测量区域的变化规律。采用空间扫描方法离体测量了35块骨样本,将超声背散射参数从空间域变换到空间频率域。结果表明,超声背散射参数的主要空间频率成分集中于低频部分;空间频率域超声背散射参量最大值(MASF)与骨矿密度等参数具有中高度显著相关性(R2=0.45~0.83,p0.001);空间频率域超声背散射参量衰减系数(AC)也与松质骨密度及结构特征有显著相关性(R2=0.41~0.72,p0.001)。研究表明空间频率域变换方法有助于明确超声背散射信号随测量ROI的变化规律,空间频率域的超声背散射相关新参量评价松质骨状况具有可行性。     

Ultrasonic propagation properties (@ 100 MHz) in excessively fatty rat liver

The effects on the ultrasonic propagation properties of livers of the addition of 1% orotic acid to rat diets were examined. In rats, dietary orotic acid exerts several effects on lipid metabolism; its overall consequence is that excessively high hepatic fat concentrations are built up over a short period of time, thus making this an ideal model to study the ultrasonic propagation properties as a function of sequential development of fatty liver. Over a 16-day period on the orotic acid diet, the supplemented rat liver lipid concentrations increased from a normal range of 2%-4% to the lower 20's%; hepatic water concentration decreased from a normal value of approximately 70% to approximately 50%; total protein concentration decreased slightly from a normal range of 17%-20% to 11%-16%; and rat liver weight increased from approximately 11 g to around 20 g. Ultrasonic attenuation coefficient and speed were assessed in liver tissue with the scanning laser acoustic microscope at 100 MHz. As hepatic lipid increased, ultrasonic attenuation at 100 MHz increased temporally from a normal range of 12-14 dB/mm to a maximum of 54 dB/mm and ultrasonic speed decreased from a normal range of 1553-1584 m/s to a minimum of 1507 m/s. Multivariant linear regression was used in the analysis of covariance to fit the least-squares estimates to the linear regression model. Strong correlates of ultrasonic speed with both water concentration and fat concentration in the liver were observed.     

Frequency scanning ultrasonic pulse echo reflectometer

The frequency scanning ultrasonic pulse echo reflectometer (FSUPER) is a device which can be used to measure the ultrasonic velocity, attenuation coefficient and specific acoustic impedance of liquid samples as a function of frequency (0.3–6 MHz).     

Frequency dependence of acoustic parameters of freshly excised tissues of Sprague Dawley rats

A modified version of the pulse echo technique was used to measure the velocity of propagation and attenuation of ultrasound in excised tissue of young-adult Sprague-Dawley rats. The measurements were made at ultrasonic frequencies of 1.0, 2.25, 5.0, 7.5 and 10.0 MHz. The temperature of the tissues was monitored continuously to within ± 0.1°C of the ambient temperature. The acoustic parameters were measured in the liver, kidney, cardiac muscle and gastrocnemius muscle. All measurements were carried out in the near field region of the ultrasonic beam. It was observed that the velocity of propagation in tissues showed a slight dispersion with frequency. The attenuation in tissues increased with increasing frequency.     

Velocity of ultrasonic waves in ferrocomposites

The velocity of ultrasonic waves with a frequency of 3 MHz is experimentally studied in a wide range of volume concentrations (0.1–50%) of ferrite particles in the matrix. The mean size of particles is 6 μm. The results of the study show that the concentration dependence of the velocity of ultrasonic wave propagation in ferrocomposites has three specific regions, in which the concentration coefficient of velocity changes from negative to positive passing through a minimum in the percolation region.     

Frequency-dependent ultrasonic differentiation of normal and diffusely diseased liver

The attenuation coefficient in 38 pathologically graded in vitro liver specimens was measured over a frequency range from 1.25-8 MHz and fitted to the power law model. The attenuation in the normal group (n = 17) exhibited a frequency dependence of the form 0.399f1.139; in the mild disease group (n = 13), it exhibited a dependence of the form 0.395f1.212; and in the moderate/severe disease group (n = 8), it exhibited a dependence of the form 0.391f1.325. Using a Student's t test, it is shown that, due to these differences in the frequency dependence, the statistical significance level at which the null hypothesis regarding the difference between the mean attenuation slopes of any two of these categories is rejected, is a strong function of frequency in the range of 1-4 MHz. The significance level relating to the difference between the normal and moderate/severe disease group is more than one order of magnitude better than the other categories. In all cases, no substantial improvement occurs beyond 4 MHz. It is also shown that attenuation slope values at 3 MHz confirm in vivo literature results obtained via different techniques.     

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。      

Ultrasonic backscatter from bovine tissues: variation with pathology

This is the second in a series of two papers reporting results collected on ultrasonic propagation properties, namely, velocity, attenuation, and backscatter of various mammalian tissues. In the first paper [J. Acoust. Soc. Am 78, 871 (1985)], the experimental results of five different types of normal bovine tissues were given. In this paper, results obtained for the most common bovine disease in the liver, liver abscess, and in the heart, lymphosarcoma, will be presented. These data show that the ultrasonic properties of tissues with these two types of pathologies are significantly deviated from those of normal tissues, thus providing further evidence that ultrasonic properties may be used as quantitative indicators of a certain disease for diagnostic purposes.     

Effect of local dual frequency sonication on drug distribution from polymeric nanomicelles

To overcome the side effects caused by systemic administration of doxorubicin, nanosized polymeric micelles were used in combination with dual frequency ultrasonic irradiation. These micelles release the drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. To form the drug-loaded micelles, Pluronic P-105 copolymer was used, and doxorubicin was physically loaded into stabilized micelles with an average size of 14 nm. In this study, adult female Balb/C mice were transplanted with spontaneous breast adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg doxorubicin in one of three forms: free doxorubicin, micellar doxorubicin without sonication and micellar doxorubicin with sonication. To increase cavitation yield, the tumor region was sonicated for 2.5 min at simultaneous frequencies of 3 MHz (I(SATA)=2 W/cm(2)) and 28 kHz (I(SATA)=0.04 W/cm(2)). The animals were sacrificed 24h after injection, and their tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The drug content in the tissues was determined using tissue fluorimetry (350 nm excitation and 560 nm emission), and standard drug dose curves were obtained for each tissue. The results show that in the group that received micellar doxorubicin with sonication, the drug concentration in the tumor tissue was significantly higher than in the free doxorubicin injection group (8.69 times) and the micellar doxorubicin without sonication group (2.60 times). The drug concentration in other tissues was significantly lower in the micellar doxorubicin with sonication group relative to the free doxorubicin (3.35 times) and the micellar drug without sonication (2.48 times) groups (p<0.05). We conclude that dual frequency sonication improves drug release from micelles and increases the drug uptake by tumors due to sonoporation. The proposed drug delivery system creates an improved treatment capability while reducing systemic side effects caused by drug uptake in other tissues.     

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.     

Contribution of intercellular links to ultrasonic absorption of liver tissue

The method discussed aims to characterize the ultrasonic absorption of liver tissues between 3 and 8.75 MHz by the slope of its linear variation with frequency. A transmission measuring device has been used and a data processing system has directly calculated this slope, which is reduced when the strength of intercellular links are lessened by mild treatment with trypsin, although the cells are left intact. This was performed on three batches of Wistar rats and the effect is explained mainly by reduction of the amplitude of relaxation processes dissipating energy in the cells.