Background & Aims Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening. Methods Acoustic Radiation Force Impulse (ARFI) shear wave imaging, a noninvasive method of assessing tissue stiffness, was used to evaluate liver fibrosis in 172 patients diagnosed with NAFLD. Liver shear stiffness measures in 3 different imaging locations were reconstructed and compared to the histologic features of NAFLD and AST-to-platelet ratio indices (APRI). Results Reconstructed shear stiffnesses were not associated with ballooned hepatocytes (p = 0.11), inflammation (p = 0.69), nor imaging location (p = 0.11). Using a predictive shear stiffness threshold of 4.24 kPa, shear stiffness distinguished low (fibrosis stage 0–2) from high (fibrosis stage 3–4) fibrosis stages with a sensitivity of 90% and a specificity of 90% (AUC of 0.90). Shear stiffness had a mild correlation with APRI (R2 = 0.22). BMI > 40 kg/m2 was not a limiting factor for ARFI imaging, and no correlation was noted between BMI and shear stiffness (R2 = 0.05). Conclusions ARFI imaging is a promising imaging modality for assessing the presence or absence of advanced fibrosis in patients with obesity-related liver disease.

Commercially-available shear wave imaging systems measure group shear wave speed (SWS) and often report stiffness parameters applying purely elastic material models. Soft tissues, however, are viscoelastic, and higher-order material models are necessary to characterize the dispersion associated with broadband shearwaves. In this paper, we describe a robust, model-based algorithm and use a linear dispersion model to perform shearwave dispersion analysis in traditionally “difficult-to-image” subjects. In a cohort of 135 Non-Alcoholic Fatty Liver Disease patients, we compare the performance of group SWS with dispersion analysis-derived phase velocity c(200 Hz) and dispersion slope dc/df parameters to stage hepatic fibrosis and steatosis. AUROC analysis demonstrates correlation between all parameters (group SWS, c(200 Hz), and, to a lesser extent dc/df) and fibrosis stage, while no correlation was observed between steatosis stage and any of the material parameters. Interestingly, optimal AUROC threshold SWS values separating advanced liver fibrosis (≥F3) from mild-to-moderate fibrosis (≤F2) were shown to be frequency dependent, and to increase from 1.8 to 3.3 m/s over the 0–400 Hz shearwave frequency range.

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The stiffness of tissue can be quantified by measuring the shear wave speed (SWS) within the medium. Ultrasound is a real-time imaging modality capable of tracking the propagation of shear waves in soft tissue. Time-of-flight (TOF) methods have previously been shown to be effective for quantifying SWS from ultrasonically tracked displacements. However, the application of these methods to in vivo data is challenging due to the presence of additional sources of error, such as physiological motion, or spatial inhomogeneities in tissue. This paper introduces the use of random sample consensus (RANSAC), a model fitting paradigm robust to the presence of gross outlier data, for estimating the SWS from ultrasonically tracked tissue displacements in vivo. SWS reconstruction is posed as a parameter estimation problem, and the RANSAC solution to this problem is described. Simulations using synthetic TOF data show that RANSAC is capable of good stiffness reconstruction accuracy (mean error 0.5 kPa) and precision (standard deviation 0.6 kPa) over a range of shear stiffness (0.6 -10 kPa) and proportion of inlier data (50 -95%). As with all TOF SWS estimation methods, the accuracy and precision of the RANSAC reconstructed shear modulus decreases with increasing tissue stiffness. The RANSAC SWS estimator was applied to radiation force induced shear wave data from 123 human patient livers acquired with a modified SONOLINE Antares ultrasound system (Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA) in a clinical setting before liver biopsy was performed. Stiffness measurements were not possible in 19 patients due to the absence of shear wave propagation inside the liver. The mean liver stiffness for the remaining 104 patients ranged from 1.3 -24.2 kPa, and the proportion of inliers for the successful reconstructions ranged between 42 -99%. Using RANSAC for SWS estimation improved the diagnostic accuracy of liver stiffness for delineating fibrosis stage when compared to ordinary least squares (OLS) without outlier removal (AUROC = 0.94 for F≥ 3 and AUROC = 0.98 for F= 4). These results show that RANSAC is a suitable method for estimating the SWS from noisy in vivo shear wave displacements tracked by ultrasound.

A 2D matrix ultrasound array is used to monitor acoustic radiation force impulse (ARFI) induced shear wave propagation in 3D in excised canine muscle. From a single acquisition, both the shear wave phase and group velocity can be calculated to estimate the shear wave speed (SWS) along and across the fibers, as well as the fiber orientation in 3D. The true fiber orientation found using the 3D Radon Transform on B-mode volumes of the muscle was used to verify the fiber direction estimated from shear wave data. For the simplified imaging case when the ARFI push can be oriented perpendicular to the fibers, the error in estimating the fiber orientation using phase and group velocity measurements was 3.5 ±2.6° and 3.4 ±1.4° (mean ± standard deviation), respectively, over six acquisitions in different muscle samples. For the more general case when the push is oblique to the fibers, the angle between the push and the fibers is found using the dominant orientation of the shear wave displacement magnitude. In 30 acquisitions on six different muscle samples with oblique push angles up to 40°, the error in the estimated fiber orientation using phase and group velocity measurements was 5.4±2.9° and 5.3±3.2°, respectively, after estimating and accounting for the additional unknown push angle. Either the phase or group velocity measurements can be used to estimate fiber orientation and SWS along and across the fibers. Although it is possible to perform these measurements when the push is not perpendicular to the fibers, highly oblique push angles induce lower shear wave amplitudes which can cause inaccurate SWS measurements.