Ned C. Rouze

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease

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 three 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 4.24kPa, 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 (R(2)=0.22). BMI>40kg/m(2) was not a limiting factor for ARFI imaging, and no correlation was noted between BMI and shear stiffness (R(2)=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.

Robust estimation of time-of-flight shear wave speed using a radon sum transformation

Time-of-flight methods allow quantitative measurement of shear wave speed (SWS) from ultrasonically tracked displacements following impulsive excitation in tissue. However, application of these methods to in vivo data are challenging because of the presence of gross outlier data resulting from sources such as physiological motion or spatial inhomogeneities. This paper describes a new method for estimating SWS by considering a solution space of trajectories and evaluating each trajectory using a metric that characterizes wave motion along the entire trajectory. The metric used here is found by summing displacement data along the trajectory as in the calculation of projection data in the Radon transformation. The algorithm is evaluated using data acquired in calibrated phantoms and in vivo human liver. Results are compared with SWS estimates using a random sample consensus (RANSAC) algorithm described by Wang et al. Good agreement is found between the Radon sum and RANSAC SWS estimates with a correlation coefficient of greater than 0.99 for phantom data and 0.91 for in vivo liver data. The Radon sum transformation is suitable for use in situations requiring real-time feedback and is comparably robust to the RANSAC algorithm with respect to outlier data.

IMPROVING THE ROBUSTNESS OF TIME-OF-FLIGHT BASED SHEAR WAVE SPEED RECONSTRUCTION METHODS USING RANSAC IN HUMAN LIVER IN VIVO

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 physiologic motion or spatial inhomogeneities in tissue. This article 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 to 24.2 kPa and the proportion of inliers for the successful reconstructions ranged between 42% to 99%. Using RANSAC for SWS estimation improved the diagnostic accuracy of liver stiffness for delineating fibrosis stage compared with ordinary least squares (OLS) without outlier removal (AUROC = 0.94 for F >or= 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.

Parameters affecting the resolution and accuracy of 2-D quantitative shear wave images

Time-of-flight methods allow quantitative measurement of shear wave speed (SWS) from ultrasonically tracked displacements following impulsive acoustic radiation force excitation in tissue. In heterogeneous materials, reflections at boundaries can distort the wave shape and confound determination of the wave arrival time. The magnitude of these effects depends on the shear wavelength of the excitation, the kernel size used to calculate the SWS, and the method used to determine the wave arrival time. In this study, we perform a parametric analysis of these factors using finite element modeling of the tissue response and simulated ultrasonic tracking. Two geometries are used, a stiff vertical layer and a stiff spherical inclusion, each in a uniform background. Wave arrival times are estimated using the peak displacement, peak slope of the leading edge, and cross-correlation methods. Results are evaluated in terms of reconstruction accuracy, resolution, contrast, and contrast-to-noise ratio of reconstructed SWS images. Superior results are obtained using narrower excitation widths and arrival time estimators which identify the leading edge of the propagating wave. The optimal kernel size is determined by a tradeoff between improved accuracy for larger kernels at the expense of spatial resolution.

Derivation and analysis of viscoelastic properties in human liver: impact of frequency on fibrosis and steatosis staging

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 shear waves. In this paper, we describe a robust, model-based algorithm and use a linear dispersion model to perform shear wave 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. Area under the ROC curve (AUROC) analysis demonstrates correlation between all parameters [group SWS, c(200 Hz), and, to a lesser extent dc/df ] and fibrosis stage, whereas 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 to 400 Hz shear wave frequency range.

Imaging Transverse Isotropic Properties of Muscle by Monitoring Acoustic Radiation Force Induced Shear Waves Using a 2-D Matrix Ultrasound Array

A 2-D matrix ultrasound array is used to monitor acoustic radiation force impulse (ARFI) induced shear wave propagation in 3-D 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 3-D. The true fiber orientation found using the 3-D 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.

RSNA/QIBA: Shear wave speed as a biomarker for liver fibrosis staging

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

On the precision of time-of-flight shear wave speed estimation in homogeneous soft solids: initial results using a matrix array transducer

A system capable of tracking radiation-force-induced shear wave propagation in a 3-D volume using ultrasound is presented. In contrast to existing systems, which use 1-D array transducers, a 2-D matrix array is used for tracking shear wave displacements. A separate single-element transducer is used for radiation force excitation. This system allows shear wave propagation in all directions away from the push to be observed. It is shown that for a limit of 64 tracking beams, by placing the beams at the edges of the measurement region of interest (ROI) at multiple directions from the push, time-of- flight (TOF) shear wave speed (SWS) measurement uncertainty can theoretically be reduced by 40% compared with equally spacing the tracking beams within the ROI along a single plane, as is typical when using a 1-D array for tracking. This was verified by simulation, and a reduction of 30% was experimentally observed on a homogeneous phantom. Analytical expressions are presented for the relationship between TOF SWS measurement uncertainty and various shear wave imaging parameters. It is shown that TOF SWS uncertainty is inversely proportional to ROI size, and inversely proportional to the square root of the number of tracking locations for a given distribution of beam locations relative to the push. TOF SWS uncertainty is shown to increase with the square of the SWS, indicating that TOF SWS measurements are intrinsically less precise for stiffer materials.

Finite element modeling of impulsive excitation and shear wave propagation in an incompressible, transversely isotropic medium

Elastic properties of materials can be measured by observing shear wave propagation following localized, impulsive excitations and relating the propagation velocity to a model of the material. However, characterization of anisotropic materials is difficult because of the number of elasticity constants in the material model and the complex dependence of propagation velocity relative to the excitation axis, material symmetries, and propagation directions. In this study, we develop a model of wave propagation following impulsive excitation in an incompressible, transversely isotropic (TI) material such as muscle. Wave motion is described in terms of three propagation modes identified by their polarization relative to the material symmetry axis and propagation direction. Phase velocities for these propagation modes are expressed in terms of five elasticity constants needed to describe a general TI material, and also in terms of three constants after the application of two constraints that hold in the limit of an incompressible material. Group propagation velocities are derived from the phase velocities to describe the propagation of wave packets away from the excitation region following localized excitation. The theoretical model is compared to the results of finite element (FE) simulations performed using a nearly incompressible material model with the five elasticity constants chosen to preserve the essential properties of the material in the incompressible limit. Propagation velocities calculated from the FE displacement data show complex structure that agrees quantitatively with the theoretical model and demonstrates the possibility of measuring all three elasticity constants needed to characterize an incompressible, TI material.

An analytic, Fourier domain description of shear wave propagation in a viscoelastic medium using asymmetric Gaussian sources

Recent measurements of shear wave propagation in viscoelastic materials have been analyzed by constructing the two-dimensional Fourier transform (2D-FT) of the spatial-temporal shear wave signal and using an analysis procedure derived under the assumption the wave is described as a plane wave, or as the asymptotic form of a wave expanding radially from a cylindrically symmetric source. This study presents an exact, analytic expression for the 2D-FT description of shear wave propagation in viscoelastic materials following asymmetric Gaussian excitations and uses this expression to evaluate the bias in 2D-FT measurements obtained using the plane or cylindrical wave assumptions. A wide range of biases are observed depending on specific values of frequency, aspect ratio R of the source asymmetry, and material properties. These biases can be reduced significantly by weighting the shear wave signal in the spatial domain to correct for the geometric spreading of the shear wavefront using a factor of x(p). The optimal weighting power p is found to be near the theoretical value of 0.5 for the case of a cylindrical source with R = 1, and decreases for asymmetric sources with R > 1.