Variability of quantitative echographic parameters of the liver: Intra- and interindividual spread, temporal-and age-related effects

The values of acoustic and image texture parameters were estimated from liver scans of healthy subjects. The values were obtained after appropriate preprocessing of the radio frequency echograms by an on-line computerized system. The preprocessing comprised a correction for the Time Gain Compensation (TGC), the beam diffraction and the frequency dependent attenuation in the Region of Interest (ROI). The intra- and interindividual variability of the parameter values appeared to be of the same order of magnitude, but significantly larger than the variability assessed by measurements of a homogeneously scattering tissue mimicking phantom. Significant temporal effects were found for all the parameters, which consistently occurred during the morning. These results are discussed in relation to the circadian rhythm of the glycogen content and of the hepatic circulation. All the parameters appeared to be significantly correlated to age. The slope of the regression ranged from 3.6% per decade (attenuation coefficient) to 7.6% per decade (mean echolevel). A tentative explanation to these results is presented: the increased stiffness of hepatic vasculature with age.     

Ultrasound attenuation imaging using compound acquisition and processing

A method that combines both spatial and frequency compounding is described for measuring attenuation in tissue. The technique applies a reference phantom to account for imaging system dependencies of echo signals. Emphasis is given to local attenuation estimates, to reduce the variance of the attenuation measurements over small regions of interest (ROI) and to enable coarse attenuation imaging. Experiments using a uniform phantom show that the standard deviation of local attenuation estimates within a ROI drops when greater degrees of compounding are applied. Attenuation images of a specially designed phantom containing inclusions with attenuation contrast illustrate the accuracy and precision of the technique.     

Echographic differentiation of histological types of intraocular melanoma

The aim of this study was to assess the differentiation of histologically different types of choroidal melanomas by means of clinical and quantitative acoustic/texture parameters of echograms. Clinical parameters were graded by morphological, kinetic and quantitative statements about the A- and B-mode echograms by a skilled diagnostician. Acoustic/texture parameters were obtained by processing and analysing radio frequency, AM-demodulated and FM-demodulated echograms. The data were preprocessed to remove influences induced by beam diffraction and focusing. The correlations between the clinical parameters were lower than 0.5 but significant in a few cases. The best set of four clinical echographic parameters enabled a retrospective classification of spindle type melanomas vs. mixed + epithelioid type melanomas with an accuracy of 77% (area under the ROC-curve of 86%). These figures do not enable, however, a prospective diagnosis. The correlations of the clinical parameters with the acoustic/texture parameters were investigated. The mutual correlations between the latter parameters were also assessed, the most significant (0.70) being between the speckle size and the slope of the linearized backscattering spectrum. The discriminant analysis performed with the best four acoustic/texture parameters (n = 30) yielded a sensitivity of 89%, a specificity of 92% and an area under the ROC-curve corresponding to a probability of correct classification of 96.6%. When using these data prospectively to classify tumours of unknown cell type (n = 21), this classification could be performed in 86% of cases.     

Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging

In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid(?) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.     

In vivo breast tissue backscatter measurements with 7.5- and 10-MHz transducers

Measurements of the ultrasound (US) backscatter coefficient (BSC) of fibroglandular and fatty breast tissues in vivo from 5.25 through 13 MHz, using the reference phantom method, are presented. Radiofrequency echo data were collected at a series of locations in the left breasts of 16 adults, age 46 to 84, and in a custom-built phantom calibrated for backscatter and attenuation. Matched regions of interest (ROIs) were then selected in these images, from which the backscatter coefficient and the backscatter frequency dependence were ratiometrically estimated, after compensation for attenuation. The mean results in fibroglandular tissues were 78.9 x 10(-3)/cm, sr at 7.2 MHz (n(ROI) = 43, n = 13) and 146 x 10(-3)/cm, sr at 10.3 MHz (n(ROI) = 19, n = 10) with frequency dependencies of f(2.28) and f(3.25). The corresponding results in subcutaneous fat were 2.59 x 10(-3)/cm, sr at 7.2 MHz (n(ROI) = 56, n = 16) and 7.08 x 10(-3)/cm, sr at 10.3 MHz (n(ROI) = 57, n = 16) with frequency dependencies of f(3.49) and f(3.43). These findings are discussed and compared to similar measurements in the literature.     

Simultaneous backscatter and attenuation estimation using a least squares method with constraints

Backscatter and attenuation variations are essential contrast mechanisms in ultrasound B-mode imaging. Emerging quantitative ultrasound methods extract and display absolute values of these tissue properties. However, in clinical applications, backscatter and attenuation parameters sometimes are not easily measured because of tissues inhomogeneities above the region-of-interest (ROI). We describe a least squares method (LSM) that fits the echo signal power spectra from a ROI to a three-parameter tissue model that simultaneously yields estimates of attenuation losses and backscatter coefficients. To test the method, tissue-mimicking phantoms with backscatter and attenuation contrast as well as uniform phantoms were scanned with linear array transducers on a Siemens S2000. Attenuation and backscatter coefficients estimated by the LSM were compared with those derived using a reference phantom method (Yao et al. 1990). Results show that the LSM yields effective attenuation coefficients for uniform phantoms comparable to values derived using the reference phantom method. For layered phantoms exhibiting nonuniform backscatter, the LSM resulted in smaller attenuation estimation errors than the reference phantom method. Backscatter coefficients derived using the LSM were in excellent agreement with values obtained from laboratory measurements on test samples and with theory. The LSM is more immune to depth-dependent backscatter changes than commonly used reference phantom methods.     

Instrument-independent acoustic backscatter coefficient imaging

This paper presents an adaptation of a method for determining acoustic backscatter coefficients to produce quantitative ultrasound images. Backscattered echo signals are recorded from a region to be imaged and backscatter coefficients are determined and related to spatial position. The values of the backscatter coefficients are then translated into a gray scale image. Testing of this imaging technique has been performed using tissue-mimicking phantoms which contain sections having backscatter coefficients different from that of the surrounding material. The technique has also been tested using a phantom in which a fat-mimicking layer is interposed between the acoustic window and the main body of the phantom. The images produced were found to be quantitatively accurate throughout the phantom, including the sections with differing backscatter. Quantitative accuracy did not suffer when the fat-mimicking layer was present.     

Quantitative tests of a three-dimensional gray scale texture model

A three-dimensional model for gray scale texture in ultrasound B-mode images has been extended to enable absolute quantitative predictions of echo signal levels and texture characteristics. The quantitative aspects of the model are tested with a phantom in which the ultrasonic scattering properties as well as the ultrasonic attenuation coefficient and the speed of sound are known as functions of frequency. Good agreement between theoretical predictions and experimental results was found in the overall brightness of B-mode images, in pixel value histograms, and in an autocorrelation function analysis of images. Passing quantitative tests is additional evidence that the model is a reliable tool for computer simulations involving many important facets of ultrasound B-mode imaging and tissue characterization.     

A thin-walled carotid vessel phantom for Doppler ultrasound flow studies

A technique is discussed for producing a robust ultrasound (US)-compatible flow phantom that consists of a thin-walled silicone-elastomer vessel with a lumen of arbitrary geometry, embedded in an agar-based tissue-mimicking material (TMM). The TMM has an acoustic attenuation of 0.56 dB cm(-1) MHz(-1) at 5 MHz, with nearly linear frequency-dependence and acoustic velocity of 1539 +/- 4 m s(-1). The vessel-mimicking material (VMM) has an acoustic attenuation of 3.5 dB cm(-1) MHz(-1) with linear frequency-dependence and an acoustic velocity of 1020 +/- 20 m s(-1). Scattering particles, which are added to the VMM to increase echogenicity and add speckle texture, lead to higher attenuation, depending on particle concentration and frequency. The VMM is stable over time, with a Young's elastic modulus of 1.3 to 1.7 MPa for strains of up to 10%, which mimics human arteries under typical physiological conditions. The phantom is sealed to prevent TMM exposure to air or water, to avoid changes to the acoustic velocity.     

Acoustic speed and attenuation coefficient in sheep aorta measured at 5-9 MHz

B-mode ultrasound (US) images from blood vessels in vivo differ significantly from vascular flow phantom images. Phantoms with acoustic properties more closely matched to those of in vivo arteries may give better images. A method was developed for measuring the speed and attenuation coefficient of US over the range 5 to 9 MHz in samples of sheep aorta using a pulse-echo technique. The times-of-flight method was used with envelope functions to identify the reference points. The method was tested with samples of tissue-mimicking material of known acoustic properties. The tissue samples were stored in Krebs physiologic buffer solution and measured over a range of temperatures. At 37 degrees C, the acoustic speed and attenuation coefficient as a function of frequency in MHz were 1600 +/- 50 ms(-1) and 1.5 +/- 4f(0.94 +/- 1.3) dB cm(-1), respectively.     

Scanning acoustic-photoacoustic microscopy using axicon transducers

A dual mode scanning acoustic microscope is investigated, yielding simultaneously images with optical and acoustical contrast. Short laser pulses are used to excite acoustic waves in a sample for the photoacoustic imaging mode. At the same time the pulses irradiate a conical target generating limited diffraction acoustic waves (X-waves) for large depth of field ultrasound imaging. For photoacoustic as well as for ultrasound imaging a focusing, ring shaped detector is applied. First phantom experiments demonstrate the possibility to acquire data for both imaging modes in a single scan, by separating images due to their different time of flight.     

Texture of B-mode echograms: 3-D simulations and experiments of the effects of diffraction and scatterer density

B-mode echograms were simulated by employing the impulse response method in transmission and reception using a discrete scatterer tissue model, with and without attenuation. The analytic signal approach was used for demodulation of the RF A-mode lines. The simulations were performed in 3-D space and compared to B-mode echograms obtained from experiments with scattering tissue phantoms. The average echo amplitude appeared to increase towards the focus and to decrease beyond it. In the focal zone, the average amplitude increased proportionally to the square root of the scatterer density. The signal to noise ratio (SNR) was found to be independent of depth, i.e., 1.91 as predicted for a Rayleigh distribution of gray levels, although a minimum was found in the focal zone at relatively low scatterer densities. The SNR continuously increased with increasing scatterer density and reached the limit of 1.91 at relatively high densities (greater than 10(4) cm-3). The lateral full width at half maximum (FWHM) of the two dimensional autocovariance function of the speckle increased continuously from the transducer face to far beyond the focus and decreased thereafter due to the diffraction effect. The lateral FWHM decreased proportionally to the logarithm of the scatterer density at low densities and reached a limit at high densities. Introduction of attenuation in the simulated tissue resulted in a much more pronounced depth dependence of the texture. The axial FWHM was independent of the distance to the transducer to a first approximation and decreased slightly with increasing scatterer density until a limit was reached at densities larger than 10(3) cm-3. This limit was in agreement with theory. The experiments confirmed the simulations and it can be concluded that the presented results are of great importance to the understanding of B-mode echograms and to the potential use of the analysis of B-mode texture for tissue characterization.     

Real-Time Ultrasound Attenuation Imaging of Diffuse Fatty Liver Disease

A method for real-time ultrasound attenuation imaging and quantification is proposed in this paper. We employed a simple algorithm for comparing two signal intensities of different frequencies to extract attenuation quantitatively. The usefulness of this method was verified by numerical simulation of the acoustic field and validated by phantom experiments. The accuracy of the results was reduced by noise in areas with a low signal-to-noise ratio, but we found that the effects of noise could be reduced by applying our noise cancellation technique or simply setting a sufficiently high gain. The estimated attenuation coefficients for clinical liver images showed acceptable correlation with the liver-to-spleen ratio of computed tomography numbers. These findings suggest that real-time attenuation parametric imaging may be able to replace CT for quantifying the degree of fatty infiltration of the liver. However, further development is needed to obtain the local attenuation distribution in cross sections with sufficient reliability.     

Attenuation smear: A ‘paradoxical’ increase in counts due to attenuation artifact

Background: Attenuation is a well recognized cause of reconstruction artifacts in SPECT imaging. Occasionally, we have noted an increase in activity extending from the apical septal portion of the ventricle in women with significant breast attenuation. Although the idea that attenuation can produce an increase in activity on the reconstructed images seems paradoxical at first, it is consistent with the process of filtered back projection. Methods: We filled a cardiac phantom with 1 mCi of Technetium-99m, placed it in a water filled anthropomorphic torso phantom and imaged it over a 180° orbit. Next, a breast phantom designed to simulate a significant degree of breast attenuation was placed on the torso phantom and imaging was repeated. The images were reconstructed first using conventional filtered back projection then with maximum likelihood. Results: When the phantoms with and without breast attenuation were reconstructed using filtered back projection and compared, the phantom with breast attenuation had a large ‘smear’ of activity extending anteriorly from the apical septal wall which was very similar to the abnormalities previously noted in clinical images; the phantom without breast attenuation had no such defect. This artifact was significantly less prominent when the images were reconstructed using the maximum likelihood technique. Conclusions: Attenuation artifact can also produce a seemingly paradoxical increase in counts on the reconstructed image but this phenomenon is consistent with the workings of filtered back projection.     

Ultrasound Phantom Using Sodium Alginate as a Gelling Agent

For medical workers, ultrasound phantoms for human soft tissue are used not only for accuracy management of ultrasound diagnosis but also to aid ultrasound‐guided needle and blind catheter insertion training without risk to real patients. For the phantoms, ultrasound characteristics and a texture are required to mimic the human soft tissue. The proposed phantom was composed of sodium alginate, calcium sulfate dihydrate, trisodium phosphate 12‐hydrate, glycerol, and water. The propagation speed, attenuation coefficient, acoustic impedance, and texture of the proposed phantom were almost the same as those of human soft tissue. Expensive chemicals and special equipment are not required.     

Texture in tissue echograms. Speckle or information?

Models of biological tissues are described in terms of acoustic parameters and of structure. Beam formation is discussed for continuous wave and pulsed modes of transducer operation and the concept of the point spread function (PSF) is introduced. The PSF is equivalent to the resolution cell, or the sampling volume, of echographic equipment. The generation of echograms from parenchymal tissues is described in terms of speckle formation due to interference at reception on the transducer. The speckle dimensions are quantitatively compared to the sampling volume of the employed transducer. It is shown that for fully developed speckle the tissue characteristics are exclusively reflected in the mean echolevel and not in the speckle size. The speckle size is, however, greatly dependent on the bandwidth, the frequency, and the geometry of the employed transducer. The attenuation by the insonated tissue yields a depth-dependent increase of mainly the lateral speckle size, in addition to the depth dependence caused by the beam formation. If the number density of scattering sites within the tissue is relatively low, the speckle characteristics are dependent on this density and, hence, tissue characterization is feasible if these characteristics are analyzed by statistical methods. These methods are gray level histogram analysis and the estimation of the autocorrelation function, ie, first and second order statistics, respectively. Structural order in tissues can be quantified by autocorrelation analysis and clinical studies on diffuse liver diseases support this conclusion. The effects of pre- and postprocessing on the detectability of focal lesions are outlined. The impact of multifocus systems and of the acquisition of radio frequency echograms on further developments of clinical echography is discussed.     

In vitro estimation of acoustic parameters of the liver and correlations with histology

Freshly excised human liver specimens (77) were investigated echographically and histologically. The echography was concerned with the acoustic parameters: speed of sound, impedance, several attenuation parameters, and the texture parameters: reflectivity and the signal to noise ratio. It was found that the speed and impedance, the attenuation parameters, and the texture parameters did not correlate with each other. The major correlation between histologic parameters was found for the focal collagen content to the parenchymal content (r = -0.72). The most important correlations of the acoustic parameters to the histologic ones were: attenuation slope to the focal collagen content (r = +0.63) and the reflectivity to the water content (r = -0.55). The most significantly separating acoustic parameters in the comparison of normal livers from focal tumours were found to be the speed, the attenuation slope, the reflectivity, and the signal to noise ratio. A Fisher discriminant analysis revealed a specificity of 91% and a sensitivity of 83% of the separation of tumours from normals when the speed of sound and two parameters of the frequency dependence of the attenuation were considered.     

能量多普勒检测乳腺肿瘤血管的准确性及误差原因分析

目的探讨能量多普勒超声检测乳腺肿瘤血管的准确性及误差原因分析。方法对73例灰阶超声诊断为乳腺肿瘤的患者行能量多普勒检查,采用图像分析软件测定肿瘤区域内的彩色像素密度,与病理血管密度对照。采用多元回归方法分析患者年龄、肿瘤的大小、距乳头距离以及后方回声衰减等对相关性研究的影响。结果①乳腺肿瘤彩色像素密度与病理小血管密度的相关系数为0.55(P<0.01)。②后方回声衰减是影响相关性的最主要因素(P=0.007),年龄次之(P=0.011),肿瘤大小和距乳头距离无显著影响(P值均大于0.05)。③校正后的彩色像素密度与病理小血管密度相关系数为0.75(P<0.01)。结论能量多普勒检测乳腺肿瘤血管的准确性主要受肿瘤后方回声衰减的影响,如以浅表部的彩色像素密度代表整个肿瘤的彩色像素密度,可以提高其准确性。     

High frequency ultrasound tissue characterization and acoustic microscopy of intracellular changes

The objective of this work is to investigate changes in the acoustic properties of cells when exposed to chemotherapy for monitoring treatment response. High frequency ultrasound spectroscopy (10-60 MHz) and scanning acoustic microscopy (0.9 GHz) were performed on HeLa cells (Ackermann et al. 1954, Masters 2002) that were exposed to the chemotherapeutic agent cisplatin. Ultrasonic radio-frequency data were acquired from pellets containing HeLa cells after exposure to cisplatin to induce apoptosis. Scanning acoustic and laser fluorescence microscopy images were recorded from single HeLa cells exposed to the same drug. Data acquisition in both cases was performed at several time points throughout the chemotherapeutic treatment for up to 27 h. In the high frequency ultrasound investigation, normalized power spectra were calculated within a region-of-interest. A 20 MHz transducer (f-number 2.35) and a 40 MHz transducer (f-number 3) were used for the data collection in the high frequency ultrasound experiments. The backscatter coefficients, integrated backscatter coefficients, mid-band fit and spectral slope were computed as a function of treatment time to monitor acoustical property changes during apoptosis. Acoustic attenuation was measured using the spectral substitution technique at all time points. Spectral parameter changes were detected after 12 h of exposure and coincided with the initiation of cell damage as assessed by optical microscopy. Integrated backscatter coefficients increased by over 100% between 0 h and 24 h of treatment, with small changes in the associated attenuation ( approximately 0.1 dB/[MHz cm]). Acoustic microscopy was performed at 0.9 GHz frequency. The cell structure was imaged using staining in laser fluorescence microscopy. All cells showed excellent correspondence between the locations of apoptotic nuclear condensation observed in optical imaging and changes in attenuation contrast in acoustic microscopy images. The time after drug exposure at which such changes occurred in the optical images were coincident with the time of changes detected in the acoustic microscopy images and the high frequency ultrasound experiments. (E-mail: Sebastian.Brand@gmail.com).     

A three dimensional model for generating the texture in B-scan ultrasound images

A three-dimensional model for production of gray scale texture in ultrasound B-mode images is described. The model computes time-dependent echo signals resulting from scattering of acoustic pulses by particles randomly distributed in an attenuating medium and transforms these signals into a gray scale image. Specific transducer and pulser-receiver characteristics are accounted for, as well as the three-dimensional nature of the problem, without loss of computational efficiency. The model generates texture that closely corresponds to that found experimentally in ultrasound images of tissue-mimicking phantoms. The dependence of the texture upon the depth of the region that was scanned and on the characteristics of the transducer-receiver system were clearly demonstrated. Good agreement between theory and experiment was found for the texture in phantoms containing simulated spherical low-scatter tumors.