The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Nonalcoholic fatty liver disease (NAFLD) is believed to affect one-third of American adults. Noninvasive methods that enable detection and monitoring of NAFLD have the potential for great public health benefits. Because of its low cost, portability, and noninvasiveness, US is an attractive alternative to both biopsy and MRI in the assessment of liver steatosis. NAFLD is qualitatively associated with enhanced B-mode US echogenicity, but visual measures of B-mode echogenicity are negatively affected by interobserver variability. Alternatively, quantitative backscatter parameters, including the hepatorenal index and backscatter coefficient, are being investigated with the goal of improving US-based characterization of NAFLD. The American Institute of Ultrasound in Medicine and Radiological Society of North America Quantitative Imaging Biomarkers Alliance are working to standardize US acquisition protocols and data analysis methods to improve the diagnostic performance of the backscatter coefficient in liver fat assessment. This review article explains the science and clinical evidence underlying backscatter for liver fat assessment. Recommendations for data collection are discussed, with the aim of minimizing potential confounding effects associated with technical and biologic variables.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

Hepatic fibrosis is a severe liver disease that has threatened human health for a long time. In order to undergo timely and adequate therapy, it is important for patients to obtain an accurate diagnosis of fibrosis. Laboratory inspection methods have been efficient in distinguishing between advanced hepatic fibrosis stages (F3, F4), but the identification of early stages of fibrosis has not been achieved. The development of proteomics may provide us with a new direction to identify the stages of fibrosis.

We established serum proteomic maps for patients with hepatic fibrosis at different stages and identified differential expression of proteins between fibrosis stages through ultra-high-performance liquid chromatography tandem mass spectrometry proteomic analysis.

From the proteomic profiles of the serum of patients with different stages of liver fibrosis, a total of 1,338 proteins were identified. Among three early fibrosis stages (control, F1, and F2), 55 differential proteins were identified, but no proteins simultaneously exhibited differential expression between control, F1, and F2. Differential proteins were detected in the comparison between different fibrosis stages. Significant differences were found between advanced fibrosis stages (F2-vs.-F3 and F3-vs.-F4) through a series of statistical analysis, including hierarchical clustering, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. The differential proteins identified by GO annotation were associated with biological processes (mainly platelet degranulation and cell adhesion), molecular functions, and cellular components.

All potential biomarkers identified between the stages of fibrosis could be key points in determining the fibrosis staging. The differences between early stages may provide a useful reference in addressing the challenge of early fibrosis staging.

The backscatter coefficient (BSC) quantifies the frequency-dependent reflectivity of tissues. Accurate estimation of the BSC is only possible with the knowledge of the attenuation coefficient slope (ACS) of the tissues under examination. In this study, the use of attenuation maps constructed using full angular spatial compounding (FASC) is proposed for attenuation compensation when imaging integrated BSCs. Experimental validation of the proposed approach was obtained using two cylindrical physical phantoms with off-centered inclusions having different ACS and BSC values than the background, and in a phantom containing an ex vivo chicken breast sample embedded in an agar matrix. With the phantom data, three different ACS maps were employed for attenuation compensation: (1) a ground truth ACS map constructed using insertion loss techniques, (2) the estimated ACS map using FASC attenuation imaging, and (3) a uniform ACS map with a value of 0.5 dBcm^{\protect \relax \special {t4ht=-}1}MHz^{\protect \relax \special {t4ht=-}1}, which is commonly used to represent attenuation in soft tissues. Comparable results were obtained when using the ground truth and FASC-estimated ACS maps in term of inclusion detectability and estimation accuracy, with averaged fractional error below 2.8 dB in both phantoms. Conversely, the use of the homogeneous ACS map resulted in higher levels of fractional error (>10 dB), which demonstrates the importance of an accurate attenuation compensation. The results with the ex vivo tissue sample were consistent with the observations using the physical phantoms, with the FASC-derived ACS map providing comparable BSC images to those formed using the ground truth ACS map and more accurate than those BSC images formed using a uniform ACS. These results suggest that BSCs can be reliably estimated using FASC when a self-consistent attenuation compensation stemming from prior estimation of an accurate ACS map is used.

The H-scan approach ('H' denoting hue, or Hermite) is a recent matched filter methodology that aims to add information to the traditional ultrasound B-scan. The theory is based on the differences in the echoes produced by different classes of reflectors or scatterers. Matched filters can be created for different types of scatterers, whereby the maximum output indicates a match, and color schemes can be used to indicate the class of scatterer responsible for echoes, providing a visual interpretation of the results. However, within the theory of weak scattering from a variety of shapes, small changes in the size of the inhomogeneous objects will create shifts in the scattering transfer function. In this paper, we argue for a general power law transfer function as the canonical model for transfer functions from most normal soft vascularized tissues, at least over some bandpass spectrum illuminated by the incident pulse. In cases where scatterer size and distributions change, this produces a corresponding shift in center frequency, along with time and frequency domain characteristics of echoes, and these are captured by matched filters to distinguish and visualize in color the major characteristics of scattering types. With this general approach, the H-scan matched filters can be set to elicit more fine grain shifts in scattering types, commensurate with more subtle changes in tissue morphology. Compensation for frequency-dependent attenuation is helpful for avoiding beam softening effects with increasing depths. Examples from phantoms and normal and pathological tissues are provided to demonstrate that the H-scan analysis and displays are sensitive to scatterer size and morphology, and can be adapted to conventional imaging systems.

What causes scattering of ultrasound from normal soft tissues such as the liver, thyroid, and prostate? Commonly, the answer is formulated around the properties of spherical scatterers, related to cellular shapes and sizes. However, an alternative view is that the closely packed cells forming the tissue parenchyma create the reference media, and the long cylindrical-shaped fluid vessels serve as the scattering sites. Under a weak scattering or Born approximation for the extracellular fluid in the vessels, and assuming an isotropic distribution of cylindrical channels across a wide range of diameters, consistent with a fractal branching pattern, some simple predictions can be made about the nature of backscatter as a function of frequency in soft tissues. Specifically, a number of plausible shapes would predict that backscatter increases as a power law of frequency, where the power law is determined by the function governing the number density of the vessels versus diameter. These results are compared with some historical models developed over the last 100 years in scattering theory and point to the need for higher spatial resolution and higher bandwidths to obtain more precise measures of the key parameters in normal tissues, and to better identify the dominant structures responsible for backscatter in everyday clinical imaging.

To assess the repeatability and reproducibility of the ultrasonic attenuation coefficient (AC) and backscatter coefficient (BSC) measured in the livers of adults with known or suspected nonalcoholic fatty liver disease (NAFLD).

The Institutional Review Board approved this Health Insurance Portability and Accountability Act-compliant prospective study; informed consent was obtained. Forty-one research participants with known or suspected NAFLD were recruited and underwent same-day ultrasound examinations of the right liver lobe with a clinical scanner by a clinical sonographer. Each participant underwent 2 scanning trials, with participant repositioning between trials. Two transducers were used in each trial. For each transducer, machine settings were optimized by the sonographer but then kept constant while 3 data acquisitions were obtained from the liver without participant repositioning and then from an external calibrated phantom. Raw RF echo data were recorded. The AC and BSC were measured within 2.6 to 3.0 MHz from a user-defined hepatic field of interest from each acquisition. The repeatability and reproducibility were analyzed by random-effects models.

The mean AC and log-transformed BSC (logBSC) were 0.94 dB/cm-MHz and -27.0 dB, respectively. Intraclass correlation coefficients were 0.88 to 0.94 for the AC and 0.87 to 0.95 for the logBSC acquired without participant repositioning. For between-trial repeated scans with participant repositioning, the intraclass correlation coefficients were 0.80 to 0.84 for the AC and 0.69 to 0.82 for the logBSC after averaging results from 3 within-trial images. The variability introduced by the transducer was less than the repeatability error.

Hepatic AC and BSC measures using a reference phantom technique on a clinical scanner are repeatable and reproducible between transducers in adults with known or suspected NAFLD.

Fine-needle aspiration (FNA) remains the gold standard for the diagnosis of thyroid cancer. However, currently, a large number of FNA biopsies result in negative or undetermined diagnosis, which suggests that better noninvasive tools are needed for the clinical management of thyroid cancer. Spectral-based quantitative ultrasound (QUS) characterizations may offer a better diagnostic management as previously demonstrated in mouse cancer models ex vivo. As a first step toward understanding the potential of QUS markers for thyroid disease management, this paper deals with the spectral-based QUS estimation of healthy human thyroids in vivo. Twenty volunteers were inspected by a trained radiologist using two ultrasonic imaging systems, which allowed them to acquire radio-frequency data spanning the 3-16-MHz frequency range. Estimates of attenuation coefficient slope (ACS) using the spectral logarithmic difference method had an average value of [Formula: see text]) with a standard deviation of [Formula: see text]. Estimates of backscatter coefficient (BSC) using the reference-phantom method had an average value of [Formula: see text] over the useful frequency range. The intersubject variability when estimating BSCs was less than 1.5 dB over the analysis frequency range. Further, the effectiveness of three scattering models (i.e., fluid sphere, Gaussian, and exponential form factors) when fitting the experimentally estimated BSCs was assessed. The exponential form factor was found to provide the best overall goodness of fit ( R² = 0.917), followed by the Gaussian ( R² = 0.807) and the fluid-sphere models ( R² = 0.752). For all scattering models used in this study, average estimates of the effective scatterer diameter were between 44 and 56 μm. Overall, an excellent agreement in the estimated attenuation and BSCs with both scanners was exhibited.

In this study, we put forward a new approach to classify early stages of fibrosis based on a multiparametric characterization using backscatter ultrasonic signals. Ultrasonic parameters, such as backscatter coefficient (Bc), speed of sound (SoS), attenuation coefficient (Ac), mean scatterer spacing (MSS), and spectral slope (SS), have shown their potential to differentiate between healthy and pathologic samples in different organs (eye, breast, prostate, liver). Recently, our group looked into the characterization of stages of hepatic fibrosis using the parameters cited above. The results showed that none of them could individually distinguish between the different stages. Therefore, we explored a multiparametric approach by combining these parameters in two and three, to test their potential to discriminate between the stages of liver fibrosis: F0 (normal), F1, F3, and/without F4 (cirrhosis), according to METAVIR Score. Discriminant analysis showed that the most relevant individual parameter was Bc, followed by SoS, SS, MSS, and Ac. The combination of (Bc, SoS) along with the four stages was the best in differentiating between the stages of fibrosis and correctly classified 85% of the liver samples with a high level of significance (p<0.0001). Nevertheless, when taking into account only stages F0, F1, and F3, the discriminant analysis showed that the parameters (Bc, SoS) and (Bc, Ac) had a better classification (93%) with a high level of significance (p<0.0001). The combination of the three parameters (Bc, SoS, and Ac) led to a 100% correct classification. In conclusion, the current findings show that the multiparametric approach has great potential in differentiating between the stages of fibrosis, and thus could play an important role in the diagnosis and follow-up of hepatic fibrosis.

Acoustic form factors have been used to model the frequency dependence of acoustic scattering in phantoms and tissues. This work demonstrates that a broad range of scatterer sizes, individually well represented by Faran theory or a Gaussian form factor, is not accurately described by a single effective scatterer from either of these models. Contributions from a distribution of discrete scatterer sizes for two different form factor functions (Gaussian form factors and scattering functions from Faran's theory) were calculated and linearly combined. Composite form factors created from Gaussian distributions of scatterer sizes centered at 50 µm with standard deviations of up to σ = 40 µm were fit to each scattering model between 2 and 12 MHz. Scatterer distributions were generated using one of two assumptions: the number density of the scatterer diameter distribution was Gaussian distributed, or the volume fraction of each scatterer diameter in the distribution was Gaussian distributed. Each simulated form factor was fit to a single-diameter form factor model for Gaussian and exponential form factors. The mean-squared error (MSE) between the composite simulated data and the best-fit single-diameter model was smaller with an exponential form factor model, compared with a Gaussian model, for distributions with standard deviations larger than 30% of the centroid value. In addition, exponential models were shown to have better ability to distinguish between Faran scattering model-based distributions with varying center diameters than the Gaussian form factor model. The evidence suggests that when little is known about the scattering medium, an exponential scattering model provides a better first approximation to the scattering correlation function for a broad distribution of spherically symmetric scatterers than when a Gaussian form factor model is assumed.

Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm(3) with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm(3) was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver.

Ultrasonic elastography, via vibration-controlled transient elastography (VCTE), enables to assess, under active mechanical constraints, the elasticity of the liver, correlating with fibrosis stages. On the other hand, the same VCTE probe can also be used in passive mode, acquiring RF lines at different locations in the liver. This paper presents a thorough evaluation of passive-mode RF spectral parameters (integrated backscatter coefficient, power spectral index, effective scattering size and spectral variance), for tissue characterization on a large cohort of volunteers with various ranges of elasticity measures. Results showed that capabilities to discriminate between liver and subcutaneous fat tissues were highly variable among spectral parameters. Furthermore, it appears that no in vivo discrimination of liver elasticity/fibrosis stage can be performed with passive RF spectral analysis, at 3.5MHz.

Applicability of ultrasound phantoms to biological tissue has been limited because most phantoms have generally used strong scatterers. The objective was to develop very weakly scattering phantoms, whose acoustic scattering properties are likely closer to those of tissues and then compare theoretical simulations and experimental backscatter coefficient (BSC) results. The phantoms consisted of agar spheres of various diameters (nominally between 90 and 212 microm), containing ultrafiltered milk, suspended in an agar background. BSC estimates were performed at two institutions over the frequency range 1-13 MHz, and compared to three models. Excellent agreement was shown between the two laboratory results as well as with the three models.

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 signals backscattered by blood. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure properties, and was termed the structure factor size and attenuation estimator (SFSAE). An ultrasound scanner equipped with a wide-band 25 MHz probe was used to insonify porcine blood sheared in both Couette and tubular flow devices. Since skin is one of the most attenuating tissue layers during in vivo scanning, four skin-mimicking phantoms with different attenuation coefficients were introduced between the transducer and the blood flow. The SFSAE gave estimates with relative errors below 25% for attenuations between 0.115 and 0.411 dBMHz and kR<2.08 (k being the wave number and R the aggregate radius). The SFSAE can be useful to examine in vivo and in situ abnormal blood conditions suspected to promote pathophysiological cardiovascular consequences.

Attenuation estimation methods for medical ultrasound are important because attenuation properties of soft tissue can be used to distinguish between benign and malignant tumors and to detect diffuse disease. The classical spectral shift method and the spectral difference method are the most commonly used methods for the estimation of the attenuation; however, they both have specific limitations. Classical spectral shift approaches for estimating ultrasonic attenuation are more sensitive to local spectral noise artifacts and have difficulty in compensating for diffraction effects because of beam focusing. Spectral difference approaches, on the other hand, fail to accurately estimate attenuation coefficient values at tissue boundaries that also possess variations in the backscatter. In this paper, we propose a hybrid attenuation estimation method that combines the advantages of the spectral difference and spectral shift methods to overcome their specific limitations. The proposed hybrid method initially uses the spectral difference approach to reduce the impact of system-dependent parameters including diffraction effects. The normalized power spectrum that includes variations because of backscatter changes is then filtered using a Gaussian filter centered at the transmit center frequency of the system. A spectral shift method, namely the spectral cross-correlation algorithm is then used to compute spectral shifts from these filtered power spectra to estimate the attenuation coefficient. Ultrasound simulation results demonstrate that the estimation accuracy of the hybrid method is better than the centroid downshift method (spectral shift method), in uniformly attenuating regions. In addition, this method is also stable at boundaries with variations in the backscatter when compared with the reference phantom method (spectral difference method). Experimental results using tissue-mimicking phantom also illustrate that the hybrid method is more robust and provides accurate attenuation estimates in both uniformly attenuating regions and across boundaries with backscatter variations. The proposed hybrid method preserves the advantages of both the spectral shift and spectral difference approaches while eliminating the disadvantages associated with each of these methods, thereby improving the accuracy and robustness of the attenuation estimation.

A problem with video signal analysis for estimating frequency-dependent ultrasonic attenuation is that relative echogenicity versus depth curves are distorted when broadband pulses are used. In this correspondence, we present results that demonstrate improved accuracy of attenuation estimates computed from B-mode or envelope data derived after narrowband (1 MHz BW) filtering at different frequencies around the center frequency of the broadband echo signal. Based on the premise that transducer center frequencies are selected in part on penetration or imaging depth requirements, simulation and experimental results for a typical ultrasound imaging system show that narrowband video signal analysis for frequencies lower than or at the center frequency of the broadband pulse provide unbiased attenuation estimation over this depth. Filtered signals above the center frequency of the pulse yield accurate results only at shallow depths.

Intraoperative ultrasound imaging of the brain is used for tumor localization and resection control. The aim of the present study was to prove whether spectral analysis of radio-frequency (rf) signals is able to improve its diagnostic capabilities by adding quantitative acoustical parameters to pure visual analysis. Meningioma was chosen as a first model because of its distinct borders during surgery as well as in ultrasound imaging. Rf signals were captured intraoperatively. Spectral analysis of rf signals was performed off-line in areas of normal brain, edematous tissue, and meningioma within the bandwidth of the transducer. At 5.0 MHz, attenuation allowed significant differentiation for normal brain versus edema (P= .00002), normal brain versus meningioma (P= .000004), and edema versus meningioma (P= .002). The slope of attenuation reached significant levels among the three groups, too. Backscatter analysis consisted of determination of the power spectral density with a significant difference for edema versus meningioma at 5 MHz (P= .02). The same was true for a relative integrated backscatter coefficient (P= .01). Frequency-dependent backscatter coefficients were estimated using a standard phantom with edema showing the highest values followed by parenchyma and meningioma. Spectral analysis of rf signals has the potential of differentiating intracranial tissues as could be shown exemplarily with meningioma in this study. If this is also true for infiltrating tumors, the method might serve as a tool to better define tumor borders, thus improving the extent of resection.

Acoustic tissue properties can be estimated using texture and/or spectral parameter analysis. Spectral analysis is based on the rf-signals whose frequency-content is commonly neglected in conventional B-mode imaging. Attenuation and backscatter values of normal brain tissue were analyzed. Unprocessed rf-data of 20 patients were sampled intraoperatively after craniotomy using a modified conventional ultrasonic device (Hitachi CS 9600) and analyzed off-line by a custom-made software routine. Before parameter estimation, influences of the diffraction pattern were compensated by means of a correction function obtained using a tissue-mimicking phantom. Attenuation of white matter showed a linear frequency dependence with a slope of 0.94 +/- 0.13 dB cm(-1) MHz(-1). The spectral slope was determined using 10 distinct frequencies between 2.5 and 5.75 MHz. Backscattering properties were analyzed by determining the power spectral density (PSD) and a relative backscatter coefficient (rel BSC) against the values derived from the tissue-mimicking phantom. PSD and rel BSC values were frequency-dependent, with highest PSD values at the probe's center frequency (-75.69 +/- 8.26 dB V(2) Hz(-1)). The corresponding rel BSC value at 5 MHz was determined as 15.39 +/- 8.26 dB. Finally, backscatter coefficients (BSC) of brain tissue were computed using the known BSC of the phantom. The data provided in this study are meant to serve as a base for intended future characterization of brain tissue that potentially allows intraoperative differentiation between normal and pathologic areas and therefore provides the surgeon with additional information for defining the extent of resection in brain more precisely.

As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz.

Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed.

Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power).

Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude.

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.

Trabecular thickness within cancellous bone is an important determinant of osteoporotic fracture risk. Noninvasive assessment of trabecular thickness potentially could yield useful diagnostic information. Faran's theory of elastic scattering from a cylindrical object immersed in a fluid has been used to predict the dependence of ultrasonic backscatter on trabecular thickness. The theory predicts that, in the range of morphological and material properties expected for trabecular bone, the backscatter coefficient at 500 kHz should be approximately proportional to trabecular thickness to the power of 2.9. Experimental measurements of backscatter coefficient were performed on 43 human calcaneus samples in vitro. Mean trabecular thicknesses on the 43 samples were assessed using micro computed tomography (CT). A power law fit to the data showed that the backscatter coefficient empirically varied as trabecular thickness to the 2.8 power. The 95% confidence interval for this exponent was 1.7 to 3.9. The square of the correlation coefficient for the linear regression to the log transformed data was 0.40. This suggests that 40% of variations in backscatter may be attributed to variations in trabecular thickness. These results reinforce previous studies that offered validation for the Faran cylinder model for prediction of scattering properties of cancellous bone, and provide added evidence for the potential diagnostic utility of the backscatter measurement.

For a wide range of applications in medical ultrasound, power spectra of received signals are approximately Gaussian. It has been established previously that an ultrasound beam with a Gaussian spectrum propagating through a medium with linear attenuation remains Gaussian. In this paper, Gaussian transformations are derived to model the effects of scattering (according to a power law, as is commonly applicable in soft tissues, especially over limited frequency ranges) and gating (with a Hamming window, a commonly used gate function). These approximations are shown to be quite accurate even for relatively broad band systems with fractional bandwidths approaching 100%. The theory is validated by experiments in phantoms consisting of glass particles suspended in agar.

In vivo attenuation and backscatter coefficients of normal human forearm dermis and subcutaneous fat were determined in the ranges 14 to 50 MHz and 14 to 34 MHz, respectively. Data were collected using three different transducers to ensure that results were independent of the measurement system. Attenuation coefficient was obtained by computing spectral slopes vs. depth, with the transducers axially translated to minimize diffraction effects. Backscatter coefficient was obtained by compensating recorded backscatter spectra for system-dependent effects and, additionally, for one transducer using the reference phantom technique. Good agreement was seen between the computed attenuation and backscatter results from the different transducers/methods. The attenuation coefficient of the forearm dermis was well described by a linear dependence with a slope that ranged between 0.08 to 0.39 (median = 0.21) dB mm(-1) MHz(-1). The backscatter coefficient of the dermis was generally in the range 10(-3) to 10(-1) Sr(-1) mm(-1) and showed an increasing trend with frequency. No significant differences in attenuation coefficient slope between the forearm dermis and fat were noted. Within the range of 14 to 34 MHz, the ratio of integrated (average) backscatter of dermis to that of fat ranged from 1.03 to 87.1 (median = 6.45), indicating significantly higher backscatter for dermis than for fat. Data were also recorded at the fingertip where the attenuation coefficient slope of the dermis was seen to be higher than that at the forearm.

The use of liquid brominated hydrocarbons to form a planar reflecting interface with water is described. Gravity-based planar reflecting surfaces with known reflection coefficients can be used in system characterization for quantitative ultrasonics, and a set of surfaces with a range of reflection coefficients allows calibration of the output power and receiver gain of ultrasonic imaging systems. The substances reported here are immiscible in water and form interfaces with water, resulting in a broad range of acoustic reflection coefficients. Reflection coefficients were measured at temperatures from 18-24 degrees C for "pure" substances and for mixtures of two brominated hydrocarbons. Results show that reflection coefficients are weakly dependent on temperature and that, at a specific temperature, a significant range of arbitrarily small reflection coefficients is available, in the case of the mixtures, by the appropriate choice of weight-percents of the two brominated hydrocarbons.

The present study was undertaken in order to investigate the use of calcaneal ultrasonic backscatter for the application of diagnosis of osteoporosis. Broadband ultrasonic attenuation (BUA), speed of sound (SOS), the average backscatter coefficient (ABC), and the hip bone mineral density (BMD) were measured in calcanea in 47 women (average age: 58 years, standard deviation: 13 years). All three ultrasound variables had comparable correlations with hip BMD (around 0.5). As reported previously by others, BUA and SOS were rather highly correlated with each other. The logarithm of the ABC was only moderately correlated with the other two. The three ultrasound parameters exhibited similar moderate negative correlations with age. These results taken collectively suggest that the ABC may carry important diagnostic information independent of that contained in BUA and SOS and, therefore, may be useful as an adjunct measurement in the diagnosis of osteoporosis.

A theoretical formulation for the profile of the integrated backscatter coefficient (IBC) is derived. This new formulation is based on a theoretical treatment by Chen et al. [1]. It includes correction for the diffraction of the ultrasonic beam and correction for the non-ideal nature of the reference signal. The inclusion of these correction factors permits accurate quantitative profiling of the IBC over the transducer focal zone. Experimental measurements are first performed on well-calibrated vessel-equivalent phantom materials and subsequently on human coronary arteries in vitro. A spherically focused 50.0 MHz f/1.83 transducer is used. IBC profiles are shown for three samples that are representative of early, mid, and advanced atherosclerotic coronary disease. The IBC profiles clearly differentiate the arterial tissues. However, variation between samples with histologically confirmed intimal thickening (N = 24) was large. The mean IBC (+/- 1 standard deviation), in (Sr.mm)-1, for media, adventitia, and thickened intima were 3.86 x 10(-3), 1.53 x 10(-2), and 2.24 x 10(-2), respectively. The mean IBC of thickened intima is larger than previous measurements obtained from femoral arteries, and the mean IBC for media and adventitia layers are lower, reflecting differences in tissue composition between coronary and femoral vessels.

Ultrasonic attenuation and sound speed have been investigated in trabecular bone by numerous authors. Ultrasonic backscatter has received much less attention. To investigate relationships among these three ultrasonic parameters and bone mineral density (BMD), 30 defatted human calcanei were investigated in vitro. Normalized broadband ultrasonic attenuation (nBUA), sound speed (SOS), and logarithm of ultrasonic backscatter coefficient (LBC) were measured. Bone mineral density was assessed using single-beam dual energy x-ray absorptiometry (DEXA). The correlation coefficients of least squares linear regressions of the three individual ultrasound (US) parameters with BMD were 0.84 (nBUA), 0.84 (SOS) and 0.79 (LBC). The 95% confidence intervals for the correlation coefficients were 0. 69-0.92 (nBUA), 0.68-0.92 (SOS) and 0.60-0.90 (LBC). The correlations among pairs of US variables ranged from 0.63-0.79. Variations in nBUA accounted for r(2) = 62% of the variations in LBC. Variations in SOS accounted for r(2) = 40% of the variations in LBC. These results suggest that ultrasonic backscattering properties may contain substantial information not already contained in nBUA and SOS. A multiple regression model including all three US variables was somewhat more predictive of BMD than a model including only nBUA and SOS.

There are now diagnostic ultrasonic imaging devices that operate at very high frequencies (VHF) of 20 MHz and beyond for clinical applications in ophthalmology, dermatology, vascular surgery, endoluminal imaging and small animal imaging. To be able to better interpret these images and to further the development of these devices, knowledge of ultrasonic attenuation and scattering of biological tissues in this frequency range is crucial. Attenuation and backscatter coefficients (BSCs) of bovine tissues in the frequency range of 10 to 30 MHz were measured, respectively, using a standard substitution method for attenuation measurements and a modified narrow-band substitution method for scattering measurements. A modified substitution method for scattering measurements has to be used at high frequencies because unfocused transducers due to their decreased sensitivity cannot be used in the simple substitution method. In the modified method, the flat reflector is substituted by a particulate reference medium whose BSC is well-known and documented; in this case, a red cell suspension. In this paper, experimental results on BSC and attenuation coefficient measured between 10 and 30 MHz are reported. The frequency dependence of backscatter of the selected bovine tissues ranges from 2.4 to 3.5, whereas attenuation is observed to be still approximately linearly proportional to frequency. The BSC measured with the modified method is in good agreement with those obtained with the standard method between 10 and 20 MHz.

Although bone sonometry has been demonstrated to be useful in the diagnosis of osteoporosis, much remains to be learned about the processes governing the interactions between ultrasound and bone. In order to investigate these processes, ultrasonic attenuation and backscatter in two orientations were measured in 43 human calcaneal specimens in vitro at 500 kHz. In the mediolateral (ML) orientation, the ultrasound propagation direction is approximately perpendicular to the trabecular axes. In the anteroposterior (AP) orientation, a wide range of angles between the ultrasound propagation direction and trabecular axes is encountered. Average attenuation slope was 18% greater while average backscatter coefficient was 50% lower in the AP orientation compared with the ML orientation. Backscatter coefficient in both orientations approximately conformed to a cubic dependence on frequency, consistent with a previously reported model. These results support the idea that absorption is a greater component of attenuation than scattering in human calcaneal trabecular bone.

Backscatter and attenuation coefficients were measured from 24 human calcanei in vitro. The logarithm of the backscatter coefficient at 500 kHz showed moderate correlations with bone mineral density (r=0.81, 95% confidence interval: 0.59-0.91) and attenuation (r=0.79, 95% CI: 0.56-0.91). These results suggest that backscatter measurements may be useful in the diagnosis of osteoporosis.

A model describing the frequency dependence of backscatter coefficient from trabecular bone is presented. Scattering is assumed to originate from the surfaces of trabeculae, which are modeled as long thin cylinders with radii small compared with the ultrasonic wavelength. Experimental ultrasonic measurements at 500 kHz, 1 MHz, and 2.25 MHz from a wire target and from trabecular bone samples from human calcaneus in vitro are reported. In both cases, measurements are in good agreement with theory. For mediolateral insonification of calcaneus at low frequencies, including the typical diagnostic range (near 500 kHz), backscatter coefficient is proportional to frequency cubed. At higher frequencies, the frequency response flattens out. The data also suggest that at diagnostic frequencies, multiple scattering effects on the average are relatively small for the samples investigated. Finally, at diagnostic frequencies, the data suggest that absorption is likely to be a larger component of attenuation than scattering.

Adequate correction for diffraction effects is critical to the measurement of device-independent acoustical parameters. This correction is especially important in situations where strongly focused beams are used in the measurements. Diffraction correction function profiles, for two spherically-focused high frequency transducers (50 MHz, focal distance 5.7 mm, f/number of 1.7 and 29 MHz, focal distance 10.0 mm, f/2), were determined using experimental and theoretical approaches. Experimental measurements are based on established approaches using the power backscattered by an ultrasonic tissue-equivalent calibrating phantom. These results are compared to a recently-published theoretical model. Excellent agreement between the experiment and theory is achieved. No statistically-significant difference in mean backscattered power is found between the experimental and theoretical approaches. The use of a simple normalization procedure (termed 'diffraction correction') involving the ratio of the mean power backscattered from the sample to the power for reflection from a plane reflector at the same depth, is shown to introduce significant errors.

The goal of this project was to investigate the utility of ultrasonic backscatter for the assessment of bone status. Ultrasound offers a low-cost, portable, nonionizing alternative or complement to common X-ray- or radioisotope (gamma ray)-based methods of bone densitometry. Ultrasonic backscatter may provide useful information not revealed by ultrasonic attenuation and sound-speed densitometers. Backscatter is sensitive to microstructural variations in acoustic impedance and should therefore provide information regarding architecture (which is related to fracture risk), as well as density. Ultrasonic backscatter at 2.25 MHz and CT bone densitometric data have been acquired from 10 healthy human volunteers. The degree of correlation between CT and ultrasonic backscatter is high (r = 0.87, p < 0.001). The envelope signal-to-noise ratio was 1.81 +/- 0.08 (mean +/- standard deviation). This suggests that the number of scatterers per resolution cell is large, the radiofrequency signal approximately obeys circular Gaussian statistics, and the envelope obeys Rayleigh statistics. These results indicate promise for ultrasonic backscatter as a substitute for or an adjunct to other ultrasonic measurements (attenuation and sound speed) and X-ray measurements for the assessment of bone status.

Quantitative ultrasonic tissue characterization using backscattered high-frequency intravascular ultrasound could provide a basis for the objective identification of lesions in vivo. Representation of local measurements of quantitative ultrasonic parameters in a conventional image format should facilitate their interpretation and thus increase their clinical utility. Toward this goal, the apparent integrated backscatter, the slope of attenuation (25-56 MHz) and the value of the attenuation on the linear fit at 37.5 MHz were measured using the backscattered radio frequency signals from in vitro human aortae. Local estimations of these ultrasonic parameters from both normal and atherosclerotic aortic segments were displayed in a B-scan format. The morphological features of these parametric images corresponded well to features of histological images of the same regions. The attenuation from 25-56 MHz of seven segments of the medial layer (both with and without overlying atheroma) were measured using the multinarrow-band backscatter method. The average attenuation in the media at 24 degrees C +/- 3 degrees C was 45 +/- 16 dB/cm at 25 MHz and 102 +/- 13 dB/cm at 50 MHz. This work represents progress toward the development of quantitative imaging methods for intravascular applications.

The average size of acoustic scatterers and the integrated backscatter coefficient of kidney cortex were measured in vivo from 2-4 MHz for a group of 50 normal adult volunteers. Our goal was to determine the sensitivity of the ultrasonic measurements under clinical conditions by identifying biologic sources of estimation uncertainty. Based on 10 measurements on each kidney of each volunteer, the average glomerular diameter for the group was found to be 216 +/- 27 microns (SD). Glomerular size was found to correlate with body surface area (r = 0.4), and the ratio of glomerular surface area to body surface area (GSA/BSA) was found to be constant throughout normal adult life with GSA/BSA = (8.24 +/- 1.35) x 10(-8) (SD). These results are consistent with histologic analyses found in the literature. Within an individual, 7% standard errors in GSA/BSA are typical. Biologic variability dominates the variance in scatterer size estimates in a group not matched for BSA, where it accounts for 47% of the variance. In a group of individuals matched for BSA, biologic variability accounts for only 21% of the variance; day-to-day variability accounts for 35% of the variance; and experimental parameters account for the remainder. If a deviation greater than 2 x SD is considered abnormal, then this technique can potentially detect changes in glomerular diameter as small as 30 microns within an individual. To detect abnormal GSA/BSA values for an individual, GSA/BSA would have to differ from the mean for that group by about 3.6 x 10(-8) or about 40%. Therefore, at this time scatterer size estimates appear most reliable for tracking the progression of disease and treatment for an individual over time.