Frequency-dependent attenuation and backscatter coefficients in bovine trabecular bone from 0.2 to 1.2 MHz

The frequency-dependent attenuation and backscatter coefficients were measured in 25 bovine femoral trabecular bone samples from 0.2 to 1.2 MHz. When the average attenuation coefficient was fitted to a nonlinear power law α(f)=α(0)+α(1)f(n), the exponent n was found to be 1.65. In contrast, the average backscatter coefficient was fitted to a power law η(f)=η(1)f(n) and the exponent n was measured as 3.25. The apparent bone density was significantly correlated with the parameter α(1) (0.2-0.7 MHz: r = 0.852, 0.6-1.2 MHz: r = 0.832) as well as the backscatter coefficient (0.5 MHz: r = 0.751, 1.0 MHz: r = 0.808).     

Theoretical and phantom based investigation of the impact of sound speed and backscatter variations on attenuation slope estimation

Quantitative ultrasound features such as the attenuation slope, sound speed and scatterer size, have been utilized to evaluate pathological variations in soft tissues such as the liver and breast. However, the impact of variations in the sound speed and backscatter due to underlying fat content or fibrotic changes, on the attenuation slope has not been addressed. Both numerical and acoustically uniform tissue-mimicking experimental phantoms are used to demonstrate the impact of sound speed variations on attenuation slope using clinical real-time ultrasound scanners equipped with linear array transducers. Radiofrequency data at center frequencies of 4 and 5 MHz are acquired for the experimental and numerical phantoms respectively. Numerical phantom sound speeds between 1480 and 1600 m/s in increments of 20 m/s for attenuation coefficients of 0.3, 0.4, 0.5, 0.6, and 0.7 dB/cm/MHz are simulated. Variations in the attenuation slope when the backscatter intensity of the sample is equal, 3 dB higher, and 3 dB lower than the reference is also evaluated. The sound speed for the experimental tissue-mimicking phantoms were 1500, 1540, 1560 and 1580 m/s respectively, with an attenuation coefficient of 0.5 dB/cm/MHz. Radiofrequency data is processed using three different attenuation estimation algorithms, i.e. the reference phantom, centroid downshift, and a hybrid method. In both numerical and experimental phantoms our results indicate a bias in attenuation slope estimates when the reference phantom sound speed is higher (overestimation) or lower (underestimation) than that of the sample. This bias is introduced via a small spectral shift in the normalized power spectra of the reference and sample with different sound speeds. The hybrid method provides the best estimation performance, especially for sample attenuation coefficient values lower than that of the reference phantom. The performance of all the methods deteriorates when the attenuation coefficient of the reference phantom is lower than that of the sample. In addition, the hybrid method is the least sensitive to sample backscatter intensity variations.     

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.     

Statistics of ultrasonic scatterer size estimation with a reference phantom

A theoretical expression for the variance of scatterer size estimates is derived for a modified least squares size estimator used in conjunction with a reference phantom method for backscatter coefficient measurement. A Gaussian spatial autocorrelation function is assumed. Simulations and phantom experiments were performed to verify the results for backscatter and size variances. The dependence of size estimate errors upon free experimental parameters is explored. Implications of the findings for the optimization of scatterer size estimation are discussed. The utility of scatterer size parametric imaging is examined through the signal to noise ratio comparison with standard ultrasonic B-mode imaging.     

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.     

Identification of human myocardial infarction in vitro based on the frequency dependence of ultrasonic backscatter.

It has been reported previously that acute and mature myocardial infarction in dogs can be differentiated in vitro and in vivo by ultrasonic tissue characterization based on measurement of the frequency dependence of ultrasonic backscatter. To characterize human infarction with an index of the frequency dependence of backscatter that could be obtained in patients, cylindrical biopsy specimens from 7 normal regions and 12 regions of infarction of 6 fixed, explanted human hearts in 2-deg steps around their entire circumference with a 5-MHz broadband transducer were insonified. One to six consecutive transmural levels were studied for each specimen. The dependence of apparent (uncompensated for attenuation or beam width) backscatter, /B(f)/2, on frequency (f) was computed from spectral analyses of radio-frequency data as /B(f)/2 = afn, where from theoretical considerations the magnitude of n decreases as scatterer size increases. Apparent integrated backscatter was computed as the average of /B(f)/2 from 3 to 7 MHz. The average value for n for normal tissue (0.9 +/- 0.1) exceeded that for tissue from regions of infarction (0.6 +/- 0.1; p less than 0.05). Infarct manifested a significant decrease of n from epicardial to endocardial levels (epi----mid----endo: 0.9----0.7----0.2; p less than 0.05) whereas normal tissue manifested similar values for n at each transmural level (0.8----1.1----0.9; p = NS). Average integrated backscatter across all transmural levels for infarct was significantly greater than for normal tissue (-48.3 +/- 0.5 vs -53.4 +/- 0.4 dB, infarct versus normal; p less than 0.05). The presence of fibrosis was associated with smaller values of n and greater integrated backscatter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Scatterer size estimation in pulse-echo ultrasound using focused sources: calibration measurements and phantom experiments

In a companion paper [T. A. Bigelow and W. D. O'Brien Jr., J. Acoust. Soc. Am. 116, 578 (2004)], theory, supported by simulations, showed that accurate scatterer size estimates could be obtained using highly focused sources provided that the derived generalized attenuation-compensation function was used and the velocity potential field near the focus could be approximated as a three-dimensional Gaussian. Herein, the theory is further evaluated via experimental studies. A calibration technique is developed to find the necessary equivalent Gaussian dimensions for a focused source using reflections obtained from a rigid plane scanned through the focus. Then, the theoretical analysis of focused sources is validated experimentally using three spherically focused ultrasound transducers to estimate the radius of glass beads imbedded in tissue mimicking phantoms. Both the impact of focusing (f/1, f/2, and f/4) and the effect of scatterer type (comparing glass bead results to simulation results that used scatterers with Gaussian impedance distributions) were tested. The simulated differences agree with the measured differences to within 2.5% provided that the comparison is made between the same scatterer type and sources with the same equivalent Gaussian dimensions. The improvement provided by the generalized attenuation-compensation function is greatly influenced by the type of scatterer whose size is being estimated and decreases as the wavelength dependence of the Gaussian depth of focus is reduced.     

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.     

Uncertainties in estimates of lesion detectability in diagnostic ultrasound.

Statistical properties of estimates of focal lesion detectability for medical ultrasonic imaging systems are investigated. Analytic forms for bias and variance of estimates of detectability of a lesion consisting of fully developed speckle embedded within a speckle background are derived. Bias and variance of estimates of detectability are investigated using a computer simulation and experiments on tissue-mimicking phantoms. This work offers a systematic methodology for interpreting measurements on phantoms in order to assess lesion detectability. In addition, it provides useful results which may be used to improve design of phantoms and experiments for imaging-system performance assessment.     

Absolute backscatter coefficient estimates of tissue-mimicking phantoms in the 5-50 MHz frequency range

Absolute backscatter coefficients in tissue-mimicking phantoms were experimentally determined in the 5-50 MHz frequency range using a broadband technique. A focused broadband transducer from a commercial research system, the VisualSonics Vevo 770, was used with two tissue-mimicking phantoms. The phantoms differed regarding the thin layers covering their surfaces to prevent desiccation and regarding glass bead concentrations and diameter distributions. Ultrasound scanning of these phantoms was performed through the thin layer. To avoid signal saturation, the power spectra obtained from the backscattered radio frequency signals were calibrated by using the signal from a liquid planar reflector, a water-brominated hydrocarbon interface with acoustic impedance close to that of water. Experimental values of absolute backscatter coefficients were compared with those predicted by the Faran scattering model over the frequency range 5-50 MHz. The mean percent difference and standard deviation was 54%?±?45% for the phantom with a mean glass bead diameter of 5.40 μm and was 47%?±?28% for the phantom with 5.16 μm mean diameter beads.     

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.     

In vivo attenuation and equivalent scatterer size parameters for atherosclerotic carotid plaque: Preliminary results

We have previously reported on the equivalent scatterer size, attenuation coefficient, and axial strain properties of atherosclerotic plaque ex vivo. Since plaque structure and composition may be damaged during a carotid endarterectomy procedure, characterization of in vivo properties of atherosclerotic plaque is essential. The relatively shallow depth of the carotid artery and plaque enables non-invasive evaluation of carotid plaque utilizing high frequency linear-array transducers. We investigate the ability of the attenuation coefficient and equivalent scatterer size parameters to differentiate between calcified, and lipidic plaque tissue. Softer plaques especially lipid rich and those with a thin fibrous cap are more prone to rupture and can be classified as unstable or vulnerable plaque. Preliminary results were obtained from 10 human patients whose carotid artery was scanned in vivo to evaluate atherosclerotic plaque prior to a carotid endarterectomy procedure. Our results indicate that the equivalent scatterer size obtained using Faran’s scattering theory for calcified regions are in the 120–180 μm range while softer regions have larger equivalent scatterer size distribution in the 280–470 μm range. The attenuation coefficient for calcified regions as expected is significantly higher than that for softer regions. In the frequency bandwidth ranging from 2.5 to 7.5 MHz, the attenuation coefficient for calcified regions lies between 1.4 and 2.5 dB/cm/MHz, while that for softer regions lies between 0.3 and 1.3 dB/cm/MHz.     

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.     

A novel power spectrum calculation method using phase-compensation and weighted averaging for the estimation of ultrasound attenuation

An estimation of ultrasound attenuation in soft tissues is critical in the quantitative ultrasound analysis since it is not only related to the estimations of other ultrasound parameters, such as speed of sound, integrated scatterers, or scatterer size, but also provides pathological information of the scanned tissue. However, estimation performances of ultrasound attenuation are intimately tied to the accurate extraction of spectral information from the backscattered radiofrequency (RF) signals. In this paper, we propose two novel techniques for calculating a block power spectrum from the backscattered ultrasound signals. These are based on the phase-compensation of each RF segment using the normalized cross-correlation to minimize estimation errors due to phase variations, and the weighted averaging technique to maximize the signal-to-noise ratio (SNR). The simulation results with uniform numerical phantoms demonstrate that the proposed method estimates local attenuation coefficients within 1.57% of the actual values while the conventional methods estimate those within 2.96%. The proposed method is especially effective when we deal with the signal reflected from the deeper depth where the SNR level is lower or when the gated window contains a small number of signal samples. Experimental results, performed at 5 MHz, were obtained with a one-dimensional 128 elements array, using the tissue-mimicking phantoms also show that the proposed method provides better estimation results (within 3.04% of the actual value) with smaller estimation variances compared to the conventional methods (within 5.93%) for all cases considered.     

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.     

Optimization of the algorithms for estimating the ultrasonic attenuation along the propagation path

In this study, we perform statistical analysis on two methods used to estimate the total ultrasound attenuation along the propagation path from the surface of the transducer to a region of interest at a particular depth; namely, the spectral-fit method and the multiple-filter method. We derive mathematical equations for the bias and variance in the attenuation estimates as a function of region of interest (ROI) size, imaging system bandwidth, and number of independent Gaussian filters (for the multiple filter method). We use numerical simulations to validate the mathematical equations and compare the two algorithms. The results show that the variance in the total attenuation coefficient estimates obtained with the two methods are comparable, and that the estimates are unbiased. For the multiple filter method, the optimal number of Gaussian filters is two.     

Scatterer size estimation in pulse-echo ultrasound using focused sources: theoretical approximations and simulation analysis

The speckle in ultrasound images has long been thought to contain information related to the tissue microstructure. Many different investigators have analyzed the frequency characteristics of the backscattered signals to estimate the scatterer acoustic concentration and size. Previous work has been mostly restricted to unfocused or weakly focused ultrasound sources, thus limiting its implementation with diagnostically relevant fields. Herein, we derive equations capable of estimating the size of a scatterer for any reasonably focused source provided that the velocity potential field in the focal region can be approximated as a three-dimensional Gaussian beam, scatterers are a sufficient distance from the source, and the field is approximately constant across the scatterer. The calculations show that, when estimating the scatterer size, correcting for focusing requires a generalized attenuation-compensation function that includes both attenuation and focusing along the beam axis. The Gaussian approximation is validated by comparing the ideal velocity potential field for three spherically focused sources with f-numbers of 1, 2, and 4 to the Gaussian approximation for frequencies from 2 to 14 MHz. The theoretical derivations are evaluated by simulating the backscatter by using spherically focused sources (f-numbers of 1, 2, and 4) adjacent to attenuating media (0.05 to 1 dB/cm/MHz) that contain scatterers with Gaussian impedance distributions. The generalized attenuation-compensation function yielded results accurate to 7.2% while the traditional attenuation-compensation functions that neglected focusing had errors as high as 103%.     

Differentiation between acutely ischemic myocardium and zones of completed infarction in dogs on the basis of frequency-dependent backscatter

The goal of this work was to determine whether the frequency dependence of apparent backscatter coefficient (not corrected for attenuation within the myocardium) could differentiate completed, remote infarction from acute myocardial injury in vivo. Myocardial infarcts were produced in six dogs by coronary artery occlusion. One to 12 months later, acute ischemic injury was induced in each dog by ligation of a coronary artery that supplied a region of myocardium adjacent to the established infarct. Infarct, ischemic, and normal regions were interrogated with a 5-MHz, circular, 0.5-in. diam, broadband, focused, piezoelectric transducer mounted in a water-filled stand-off device placed against the exposed, beating heart. Apparent backscatter coefficients were measured over the range of frequencies from 3-7 MHz. The frequency dependence was obtained from the slope of log apparent backscatter coefficient versus log frequency. No significant difference in frequency dependence was found between normal and acutely ischemic myocardium for periods of up to 2 h of ischemia. In contrast, frequency dependence in regions of remote infarct (1.8 +/- 0.1, mean +/- standard error) was significantly lower than that in acutely ischemic or nonischemic regions (2.3 +/- 0.1) (p less than 0.01). These results suggest that remote myocardial infarction can be differentiated from acutely injured but still potentially salvageable myocardium in vivo on the basis of the frequency dependence of backscatter.     

High-frequency ultrasound scattering from microspheres and single cells

Assessing the proportion of biological cells in a volume of interest undergoing structural changes, such as cell death, using high-frequency ultrasound (20-100 MHz), requires the development of a theoretical model of scattering by any arbitrary cell ensemble. A prerequisite to building such a model is to know the scattering by a single cell in different states. In this paper, a simple model for the high-frequency acoustic scattering by one cell is proposed. A method for deducing the backscatter transfer function from a single, subresolution scatterer is also devised. Using this method, experimental measurements of backscatter from homogeneous, subresolution polystyrene microspheres and single, viable eukaryotic cells, acquired across a broad, continuous range of frequencies were compared with elastic scattering theory and the proposed cell scattering model, respectively. The resonant features observed in the backscatter transfer function of microspheres were found to correspond accurately to theoretical predictions. Using the spacing of the major spectral peaks in the transfer functions obtained experimentally, it is possible to predict microsphere diameters with less than 4% error. Such good agreement was not seen between the cell model and the measured backscatter from cells. Possible reasons for this discrepancy are discussed.     

Optimization of angular and frequency compounding in ultrasonic attenuation estimations

Previous reports have shown that the variance in ultrasound attenuation measurements is reduced when spatial and frequency compounding were applied in data acquisition and analysis. This paper investigates factors affecting the efficiency of compound attenuation imaging methods. A theoretical expression is derived that predicts the correlation between attenuation versus frequency slope (beta) estimates as a function of the increment between measurement frequencies (deltaf ) and the angular separation between beam lines (Delta (theta)). Theoretical results are compared with those from attenuation measurements on tissue-mimicking phantoms and from simulation data. Both predictions and measurement results show that the correlation between beta estimates as a function of (Delta f ) is independent of the length of the radio frequency (rf) data segment over which beta is derived. However, it decreases with an increase in the length of the data segment used in power spectra estimates. In contrast, the correlation between beta estimates as a function of delta(theta) decreases when the rf data segment length is longer or the frequency of the signal is higher. O 2005 Acoustical Society of America.