Objective. Speed of sound has previously been demonstrated to correlate with fat concentration in the liver. However, estimating speed of sound in the liver noninvasively can be biased by the speed of sound of the tissue layers overlying the liver. Here, we demonstrate a noninvasive local speed of sound estimator, which is based on a layered media assumption, that can accurately capture the speed of sound in the liver. We validate the estimator using an obese Zucker rat model of non-alcoholic fatty liver disease and correlate the local speed of sound with liver steatosis.Approach.We estimated the local and global average speed of sound noninvasively in 4 lean Zucker rats fed a normal diet and 16 obese Zucker rats fed a high fat diet for up to 8 weeks. The ground truth speed of sound and fat concentration were measured from the excised liver using established techniques.Main Results. The noninvasive, local speed of sound estimates of the livers were similar in value to their corresponding 'ground truth' measurements, having a slope ± standard error of the regression of 0.82 ± 0.15 (R²= 0.74 andp< 0.001). Measurement of the noninvasive global average speed of sound did not reliably capture the 'ground truth' speed of sound in the liver, having a slope of 0.35 ± 0.07 (R²= 0.74 andp< 0.001). Decreasing local speed of sound was observed with increasing hepatic fat accumulation (approximately -1.7 m s^-1per 1% increase in hepatic fat) and histopathology steatosis grading (approximately -10 to -13 m s^-1per unit increase in steatosis grade). Local speed of sound estimates were highly correlated with steatosis grade, having Pearson and Spearman correlation coefficients both ranging from -0.87 to -0.78. In addition, a lobe-dependent speed of sound in the liver was observed by theex vivomeasurements, with speed of sound differences of up to 25 m s^-1(p< 0.003) observed between lobes in the liver of the same animal.Significance.The findings of this study suggest that local speed of sound estimation has the potential to be used to predict or assist in the measurement of hepatic fat concentration and that the global average speed of sound should be avoided in hepatic fat estimation due to significant bias in the speed of sound estimate.

Quantitative ultrasound (QUS) has emerged as a viable tool in diagnosing and staging the onset and progression of various diseases. Within the field of QUS, shear wave elastography (SWE) has emerged as the clinical standard for quantifying and correlating the stiffness of tissue to its underlying pathology. Despite its widespread use, SWE suffers from drawbacks that limit its widespread clinical use; among these are low-frame rates, long settling times, and high sensitivity to operating conditions. Longitudinal speed of sound (SOS) has emerged as a viable alternative to SWE. We propose a framework to obtain 2D sound speed maps using a commercial ultrasound probe. A commercial ultrasound probe is localized in space and used to scan a domain of interest from multiple vantage points; the use of a reflector at the far end of the domain allows us to measure the round trip travel times to and from it. The known locations of the probe and the measured travel times are used to estimate the depth and inclination of the reflector as well as the unknown sound speed map. The use of multiple looks increases the effective aperture of the ultrasound probe and allows for a higher fidelity reconstruction of sound speed maps. We validate the framework using simulated and experimental data and propose a rigorous framework to quantify the uncertainty of the estimated sound speed maps.

Described here is a method to determine the longitudinal speed of sound in speckle-dominated ultrasound images. The method is based on the concept that the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium. The method captures the quality of the ultrasound image using two quantitative image-quality metrics: image brightness and sharpness around the intended focal zone. The proposed method requires no calibration, is computationally efficient and is deployable on commercial ultrasound systems without hardware or software modifications. Ex vivo testing on tissue-mimicking phantoms indicates the method's accuracy in predicting the true speed of sound to within 1% of ground truth values.

This study validates a non-invasive, quantitative technique to diagnose steatosis within tissue. The proposed method is based on two fundamental concepts: (i) the speed of sound in a fatty liver is lower than that in a healthy liver and (ii) the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium under examination. The method uses image brightness and sharpness as quantitative image-quality metrics to predict the true sound speed and capture the effects of fat infiltration, while accounting for the transmission through subcutaneous fat. Ex vivo testing on sheep liver, mouse livers and tissue-mimicking phantoms indicated the technique's ability to predict the true speed of sound with errors less than 0.5% and to quantify the inverse correlation between fat content and speed of sound.

Non-alcoholic fatty liver disease is a condition that is characterized by the presence of >5% fat in the liver and affects more than one billion people worldwide. If adequate and early precautions are not taken, non-alcoholic fatty liver disease can progress to cirrhosis and death. The current reference standard for detecting hepatic steatosis is a liver biopsy. However, because of the potential morbidity associated with liver biopsies, non-invasive imaging biomarkers have been extensively investigated. Magnetic resonance imaging-based methods have proven accuracy in quantifying liver steatosis; however, these techniques are costly and have limited availability. Ultrasound-based quantitative imaging techniques are increasingly utilized because of their widespread availability, ease of use and relative cost-effectiveness. Several ultrasound-based liver fat quantification techniques have been investigated, including techniques that measure changes in the acoustic properties of the liver caused by the presence of fat. In this review, we focus on quantitative ultrasound approaches and their diagnostic performance in the realm of non-alcoholic fatty liver disease.

A model and method to accurately estimate the local speed of sound in tissue from pulse-echo ultrasound data is presented. The model relates the local speeds of sound along a wave propagation path to the average speed of sound over the path, and allows one to avoid bias in the sound-speed estimates that can result from overlying layers of subcutaneous fat and muscle tissue. Herein, the average speed of sound using the approach by Anderson and Trahey is measured, and then the authors solve the proposed model for the local sound-speed via gradient descent. The sound-speed estimator was tested in a series of simulation and ex vivo phantom experiments using two-layer media as a simple model of abdominal tissue. The bias of the local sound-speed estimates from the bottom layers is less than 6.2 m/s, while the bias of the matched Anderson's estimates is as high as 66 m/s. The local speed-of-sound estimates have higher standard deviation than the Anderson's estimates. When the mean local estimate is computed over a 5-by-5 mm region of interest, its standard deviation is reduced to less than 7 m/s.

Quality assurance phantoms are made of tissue-mimicking materials (TMMs) the acoustic properties of which mimic those of soft tissue. However, the acoustic properties of many soft tissue types have not been measured at ultrasonic frequencies >9 MHz. With the increasing use of high-frequency ultrasound for both clinical and pre-clinical applications, it is of increasing interest to ensure that TMMs accurately reflect the acoustic properties of soft tissue at these higher frequencies. In this study, the acoustic properties of ex vivo brain, liver and kidney samples from 50 mice were assessed in the frequency range 12-32 MHz. Measurements were performed within 6 min of euthanasia in a phosphate-buffered saline solution maintained at 37.2 ± 0.2 °C. The measured mean values for the speed of sound for all organs were found to be higher than the International Electrotechnical Commission guideline recommended value for TMMs. The attenuation coefficients measured for brain, liver and kidney samples were compared with the results of previous studies at lower frequencies. Only the measured kidney attenuation coefficient was found to be in good agreement with the International Electrotechnical Commission guideline. The information provided in this study can be used as a baseline on which to manufacture a TMM suitable for high-frequency applications.

The speed of sound correlates well with the fat content of the liver. Therefore, non-invasive quantification of sound speed in the liver might be of diagnostic value. Here we describe a new non-invasive method that would be clinically applicable for measurement of sound speed in the liver. Sprague-Dawley rats were divided into two groups: a control group and a fatty liver group prepared by keeping the rats on a choline-deficient diet for 6 wk. The livers were subjected to pathologic and biochemical analysis; the speed of sound through the liver tissue was measured using our proposed method and a pulser-receiver as standard. Our results indicated that use of the proposed method makes it feasible to diagnose fatty liver with good accuracy on the basis of sound speed. This approach would have considerable potential for non-invasive diagnosis of fatty liver and would be a valuable adjunct to conventional liver diagnostic procedures.

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.

Radiofrequency ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. Recurrence rates after rf therapy are as high as 34-55%, due to difficulties in accurately identifying the zone of necrosis (thermal lesion) because of the low intrinsic acoustic contrast between normal and ablated liver tissue. Our goal is to provide real-time ultrasonic tracking of temperature changes over the large range of temperatures traditionally used (40-100 degrees C) in rfablation procedures using an external ultrasound transducer. Temperature estimates are obtained using a cross-correlation algorithm applied to rf ultrasound echo signal data acquired at discrete intervals during heating. Apparent tissue displacement estimates obtained at these discrete time-intervals are accumulated to obtain a cumulative displacement map, whose gradient provides after appropriate scaling provides a temperature map at the specified elapsed ablation duration. Temperature maps are used to display the initial temperature rise and to continuously update a thermal map of the treated region. In this paper, we develop calibration curves that relate the echo shift due to the change in the speed of sound and thermal expansion to the corresponding temperature increase on in-vitro tissue specimens. These calibration curves can then be utilized for the real time calibration and analysis of temperature estimates obtained from the rf echo signals during ablation. Temperature maps obtained using the calibration curve compare favorably to temperature estimates observed using the invasive thermosensor readings on the ablation electrode and previous results that utilized a linear calibration factor.

Attention coefficient and propagation speed of intercostal tissues were estimated from chest walls removed postmortem (pm) from 15 5.3+/-2.3-day-old, 19 31+/-6-day-old, and 15 61+/-3-day-old crossbred pigs. These ultrasonic propagation properties were determined from measurements through the intercostal tissues, from the surface of the skin to the parietal pleura. The chest walls were placed in a 0.9% sodium chloride solution, sealed in freezer bags, and stored at -15 degrees C prior to measurements. When evaluated, chest-wall storage time ranged between 1 and 477 days pm. All chest walls were allowed to equilibrate to 22 degrees C in a water bath prior to evaluation. There was an age dependency of the intercostal tissue propagation speed, with the speed increasing with increasing age. The attenuation coefficient of intercostal tissue was shown to be independent of the age of the pig at the discrete frequencies of 3.1 and 6.2 MHz. For pig intercostal tissues, the estimated attenuation coefficient over the 3.1-9.2 MHz frequency range was A = 1.94f(0.90) where A is in decibels per centimeter (dB/cm) and f is the ultrasonic frequency in megahertz. In order to determine if there was an effect of storage time pm on estimates of attenuation coefficient, a second experiment was conducted. Five of the youngest pig chest walls measured on day 1 pm in the first experiment were stored at 4 degrees C prior to the first evaluation then stored at -15 degrees C before being measured again at 108 days pm. There was no difference in the estimated intercostal tissue attenuation coefficient as a function of storage time pm.

Sound speed may be measured by comparing the transit time of a broadband ultrasonic pulse transmitted through an object with that transmitted through a reference water path. If the speed of sound in water and the thickness of the sample are known, the speed of sound in the object may be computed. To measure the transit time differential, a marker such as a zero-crossing, may be used. A sound speed difference between the object and water shifts all markers backward or forward. Frequency-dependent attenuation and dispersion may alter the spectral characteristics of the waveform, thereby distorting the locations of markers and introducing variations in sound-speed estimates. Theory is derived to correct for this distortion for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The theory is validated using numerical analysis, measurements on a tissue mimicking phantom, and on 24 human calcaneus samples in vitro. Variations in soft tissue-like media are generally not exceptionally large for most applications but can be substantial, particularly for high bandwidth pulses propagating through media with high attenuation coefficients. At 500 kHz, variations in velocity estimates in bone can be very substantial, on the order of 40 to 50 m/s because of the high attenuation coefficient of bone. In trabecular bone, the effects of frequency-dependent attenuation are considerable, and the effects of dispersion are negligible.