Shear Wave Speed Estimation Using Reverberant Shear Wave Fields: Implementation and Feasibility Studies

Elastography is a modality that estimates tissue stiffness and, thus, provides useful information for clinical diagnosis. Attention has focused on the measurement of shear wave propagation; however, many methods assume shear wave propagation is unidirectional and aligned with the lateral imaging direction. Any deviations from the assumed propagation result in biased estimates of shear wave speed. To address these challenges, directional filters have been applied to isolate shear waves with different propagation directions. Recently, a new method was proposed for tissue stiffness estimation involving creation of a reverberant shear wave field propagating in all directions within the medium. These reverberant conditions lead to simple solutions, facile implementation and rapid viscoelasticity estimation of local tissue. In this work, this new approach based on reverberant shear waves was evaluated and compared with another well-known elastography technique using two calibrated elastic and viscoelastic phantoms. Additionally, the clinical feasibility of this technique was analyzed by assessing shear wave speed in human liver and breast tissues, in vivo. The results indicate that it is possible to estimate the viscoelastic properties in each scanned medium. Moreover, a better approach to estimation of shear wave speed was obtained when only the phase information was taken from the reverberant waves, which is equivalent to setting all magnitudes within the bandpass equal to unity: an idealization of a perfectly isotropic reverberant shear wave field.     

Characterization of the nonlinear elastic properties of soft tissues using the supersonic shear imaging (SSI) technique: Inverse method,ex vivo and in vivo experiments

Dynamic elastography has become a new clinical tool in recent years to characterize the elastic properties of soft tissues in vivo, which are important for the disease diagnosis, e.g., the detection of breast and thyroid cancer and liver fibrosis. This paper investigates the supersonic shear imaging (SSI) method commercialized in recent years with the purpose to determine the nonlinear elastic properties based on this promising technique. Particularly, we explore the propagation of the shear wave induced by the acoustic radiation force in a stressed hyperelastic soft tissue described via the Demiray–Fung model. Based on the elastodynamics theory, an analytical solution correlating the wave speed with the hyperelastic parameters of soft tissues is first derived. Then an inverse approach is established to determine the hyperelastic parameters of biological soft tissues based on the measured wave speeds at different stretch ratios. The property of the inverse method, e.g., the existence, uniqueness and stability of the solution, has been investigated. Numerical experiments based on finite element simulations and the experiments conducted on the phantom and pig livers have been employed to validate the new method. Experiments performed on the human breast tissue and human heel fat pads have demonstrated the capability of the proposed method for measuring the in vivo nonlinear elastic properties of soft tissues. Generalization of the inverse analysis to other material models and the implication of the results reported here for clinical diagnosis have been discussed.     

Impact of Acoustic Radiation Force Excitation Geometry on Shear Wave Dispersion and Attenuation Estimates

Shear wave elasticity imaging (SWEI) characterizes the mechanical properties of human tissues to differentiate healthy from diseased tissue. Commercial scanners tend to reconstruct shear wave speeds for a region of interest using time-of-flight methods reporting a single shear wave speed (or elastic modulus) to the end user under the assumptions that tissue is elastic and shear wave speeds are not dependent on the frequency content of the shear waves. Human tissues, however, are known to be viscoelastic, resulting in dispersion and attenuation. Shear wave spectroscopy and spectral methods have been previously reported in the literature to quantify shear wave dispersion and attenuation, commonly making an assumption that the acoustic radiation force excitation acts as a cylindrical source with a known geometric shear wave amplitude decay. This work quantifies the bias in shear dispersion and attenuation estimates associated with making this cylindrical wave assumption when applied to shear wave sources with finite depth extents, as commonly occurs with realistic focal geometries, in elastic and viscoelastic media. Bias is quantified using analytically derived shear wave data and shear wave data generated using finite-element method models. Shear wave dispersion and attenuation bias (up to 15% for dispersion and 41% for attenuation) is greater for more tightly focused acoustic radiation force sources with smaller depths of field relative to their lateral extent (height-to-width ratios <16). Dispersion and attenuation errors associated with assuming a cylindrical geometric shear wave decay in SWEI can be appreciable and should be considered when analyzing the viscoelastic properties of tissues with acoustic radiation force source distributions with limited depths of field.     

Congruence of imaging estimators and mechanical measurements of viscoelastic properties of soft tissues

Biomechanical properties of soft tissues are important for a wide range of medical applications, such as surgical simulation and planning and detection of lesions by elasticity imaging modalities. Currently, the data in the literature is limited and conflicting. Furthermore, to assess the biomechanical properties of living tissue in vivo, reliable imaging-based estimators must be developed and verified. For these reasons, we developed and compared two independent quantitative methods--crawling wave estimator (CRE) and mechanical measurement (MM) for soft tissue characterization. The CRE method images shear wave interference patterns from which the shear wave velocity can be determined and hence the Young's modulus can be obtained. The MM method provides the complex Young's modulus of the soft tissue from which both elastic and viscous behavior can be extracted. This article presents the systematic comparison between these two techniques on the measurement of gelatin phantom, veal liver, thermal-treated veal liver and human prostate. It was observed that the Young's moduli of liver and prostate tissues slightly increase with frequency. The experimental results of the two methods are highly congruent, suggesting CRE and MM methods can be reliably used to investigate viscoelastic properties of other soft tissues, with CRE having the advantages of operating in nearly real time and in situ.     

Longitudinal and shear mode ultrasound propagation in human skull bone

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.     

Transvaginal Ultrasound Vibro-elastography for Measuring Uterine Viscoelasticity: A Phantom Study

The purpose of this research was to determine the feasibility of a transvaginal ultrasound vibro-elastography (TUVE) technique for generating and measuring shear wave propagation in the uterus. In TUVE, a 0.1-s harmonic vibration at a low frequency is generated on the abdomen of a subject via a handheld vibrator. A transvaginal ultrasound probe is used to measure the resulting shear wave propagation in the uterus. TUVE was evaluated on a female ultrasound phantom. The shear wave speeds in the region of interest of the uterus of the female ultrasound phantom were measured in the frequency range of 100–300 Hz. The viscoelasticity was analyzed based on the wave speed dispersion with frequency. The measurement of shear wave speed suggests that the uterus of this female ultrasound phantom is much stiffer than the human uterus. This research illustrates the feasibility of TUVE for generating and measuring shear wave propagation in the uterus of a female ultrasound phantom. We will further evaluate TUVE in patients, both normal controls and those with uterine diseases such as adenomyosis.     

Magnetomotive optical coherence elastography using magnetic particles to induce mechanical waves

Magnetic particles are versatile imaging agents that have found wide spread applicability in diagnostic, therapeutic, and rheology applications. In this study, we demonstrate that mechanical waves generated by a localized inclusion of magnetic nanoparticles can be used for assessment of the tissue viscoelastic properties using magnetomotive optical coherence elastography. We show these capabilities in tissue mimicking elastic and viscoelastic phantoms and in biological tissues by measuring the shear wave speed under magnetomotive excitation. Furthermore, we demonstrate the extraction of the complex shear modulus by measuring the shear wave speed at different frequencies and fitting to a Kelvin-Voigt model.OCIS codes: (110.4500) Optical coherence tomography, (170.6935) Tissue characterization, (260.2110) Electromagnetic optics, (350.5030) Phase, (350.0350) Other areas of optics     

Two Point Method For Robust Shear Wave Phase Velocity Dispersion Estimation of Viscoelastic Materials

Ultrasound shear wave elastography (SWE) is an imaging modality used for noninvasive, quantitative evaluation of tissue mechanical properties. SWE uses an acoustic radiation force to produce laterally propagating shear waves that can be tracked in spatial and temporal domains in order to obtain the wave velocity. One of the ways to study the viscoelasticity is through examining the shear wave velocity dispersion curves. In this paper, we present an alternative method to two-dimensional Fourier transform (2D-FT). Our unique approach (2P-CWT) considers shear wave propagation measured in two lateral locations only and uses wavelet transformation analysis. We used the complex Morlet wavelet function as the mother wavelet to filter two shear waves at different locations. We examined how the first signal position and the distance between the two locations affect the shear wave velocity dispersion estimation in 2P-CWT. We tested this new method on a digital phantom data created using the local interaction simulation approach (LISA) in viscoelastic media with and without added white Gaussian noise to the wave motion. Moreover, we tested data acquired from custom made tissue mimicking viscoelastic phantom experiments and ex vivo porcine liver measurements. We compared results from 2P-CWT with the 2D-FT technique. 2P-CWT provided dispersion curves estimation with lower errors over a wider frequency band in comparison to 2D-FT. Tests conducted showed that the two-point technique gives results with better accuracy in simulation results and can be used to measure phase velocity of viscoelastic materials.     

Effect of graphite concentration on shear-wave speed in gelatin-based tissue-mimicking phantoms

Elasticity-based imaging modalities are becoming popular diagnostic tools in clinical practice. Gelatin-based, tissue mimicking phantoms that contain graphite as the acoustic scattering material are commonly used in testing and validating elasticity-imaging methods to quantify tissue stiffness. The gelatin bloom strength and concentration are used to control phantom stiffness. While it is known that graphite concentration can be modulated to control acoustic attenuation, the impact of graphite concentration on phantom elasticity has not been characterized in these gelatin phantoms. This work investigates the impact of graphite concentration on phantom shear stiffness as characterized by shear-wave speed measurements using impulsive acoustic-radiation-force excitations. Phantom shear-wave speed increased by 0.83 (m/s)/(dB/(cm MHz)) when increasing the attenuation coefficient slope of the phantom material through increasing graphite concentration. Therefore, gelatin-phantom stiffness can be affected by the conventional ways that attenuation is modulated through graphite concentration in these phantoms.     

Attenuation of Shear Waves in Normal and Steatotic Livers

Shear wave propagation in the liver has been a robust subject of research, with shear wave speed receiving the most attention. The correlation between increased shear wave speed and increased fibrosis in the liver has been established as a useful diagnostic tool. In comparison, the precise mechanisms of shear wave attenuation, and its relation to diseased states of the liver, are less well-established. This study focused on the hypothesis that steatosis adds a viscous (lossy) component to the liver, which increases shear wave attenuation. Twenty patients’ livers were scanned with ultrasound and with induced shear wave propagation, and the resulting displacement profiles were analyzed using recently developed estimators to derive both the speed and attenuation of the shear waves within 6-cm² regions of interest. The results were compared with pathology scores obtained from liver biopsies taken under ultrasound guidance. Across these cases, increases in shear wave attenuation were linked to increased steatosis score. This preliminary study supports the hypothesis and indicates the possible utility of the measurements for non-invasive and quantitative assessment of steatosis.     

Evaluation of Robustness of Local Phase Velocity Imaging in Homogenous Tissue-Mimicking Phantoms

Shear wave elastography (SWE) is a method of evaluating mechanical properties of soft tissues. Most current implementations of SWE report the group velocity for shear wave velocity, which assumes an elastic, isotropic, homogenous and incompressible tissue. Local phase velocity imaging (LPVI) is a novel method of phase velocity reconstruction that allows for accurate evaluation of shear wave velocity at specified frequencies. This method's robustness was evaluated in 11 elastic and 8 viscoelastic phantoms using linear and curvilinear arrays. We acquired data with acoustic radiation force push beams with different focal depths and F-numbers and reconstructed phase velocity images over a wide range of frequencies. Regardless of phantom, push beam focal depth and reconstruction frequency, an F-number around 3.0 was found to produce the largest usable area in the phase velocity reconstructions. For elastic phantoms scanned with a linear array, the optimal focal depth, frequency range and maximum region of interest (ROI) were 20–30 mm, 100–400 Hz and 2.70 cm², respectively. For viscoelastic phantoms scanned with a linear array, the optimal focal depth, frequency and maximum ROI were 20–30 mm, 100–300 Hz and 1.54 cm², respectively. For the curvilinear array in the same phantoms, optimal focal depth, frequency range and maximum ROIs were 45–60 mm, 100–400 and 100–300 Hz and 1.54 cm², respectively. In further work, LPVI reconstructions from inclusion phantoms will be evaluated to simulate non-homogeneous tissues. Additionally, LPVI will be evaluated in larger-volume phantoms to account for wave reflection from the containers when using the curvilinear array.     

Dynamic measurement of soft tissue viscoelastic properties with a torsional resonator device

A new method for measuring the mechanical properties of soft biological tissues is presented. Dynamic testing is performed using a torsional resonator, whose free extremity is in contact with a tissue sample. An analytical model of a semi-infinite, homogenous, isotropic medium is used to model the shear wave propagation in the material sample and allows determining the complex shear modulus of the soft tissue. By controlling the vibration amplitude, shear strains of less than 0.2% are induced in the tissue so that the material response can be considered as linear viscoelastic. Experiments are performed at different eigenfrequencies of the torsional oscillator and the complex shear modulus is characterized in the range 1-10 kHz. In vitro experiments on bovine and porcine liver are presented in order to demonstrate the sensitivity of the proposed technique, and the reliability of the measurements is confirmed with comparative tests on synthetic material. The experiment does not damage the soft tissue and allows a fast and local measurement, these being prerequisites for future applications in vivo during open surgery.     

Quantification of Liver Viscoelasticity with Acoustic Radiation Force: A Study of Hepatic Fibrosis in a Rat Model

Ultrasound elastography, based on shear wave propagation, enables the quantitative and non-invasive assessment of liver mechanical properties such as stiffness and has been found to be feasible for and useful in the diagnosis of hepatic fibrosis. Most ultrasound elastographic methods use a purely elastic model to describe liver mechanical properties. However, to describe tissue that is dispersive and to obtain an accurate measure of tissue elasticity, the viscoelasticity of the tissue should be examined. The objective of this study was to investigate the shear viscoelastic characteristics, as measured by ultrasound elastography, of liver fibrosis in a rat model and to evaluate the diagnostic accuracy of viscoelasticity for staging liver fibrosis. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl₄); 6 rats served as controls. Liver viscoelasticity was measured in vitro using shear waves induced by acoustic radiation force. The measured mean values of liver elasticity and viscosity ranged from 0.84 to 3.45 kPa and from 1.12 to 2.06 Pa·s for fibrosis stages F0–F4, respectively. Spearman correlation coefficients indicated that stage of fibrosis was well correlated with elasticity (0.88) and moderately correlated with viscosity (0.66). The areas under receiver operating characteristic curves were 0.97 (≥F2), 0.91 (≥F3) and 1.00 (F4) for elasticity and 0.91 (≥F2), 0.79 (≥F3) and 0.74 (F4) for viscosity, respectively. The results confirmed that shear wave velocity was dispersive in frequency, suggesting a viscoelastic model to describe liver fibrosis. The study finds that although viscosity is not as good as elasticity for staging fibrosis, it is important to consider viscosity to make an accurate estimation of elasticity; it may also provide other mechanical insights into liver tissues.     

Optical coherence tomography detection of shear wave propagation in inhomogeneous tissue equivalent phantoms and ex-vivo carotid artery samples

In this work, we explored the potential of measuring shear wave propagation using optical coherence elastography (OCE) in an inhomogeneous phantom and carotid artery samples based on a swept-source optical coherence tomography (OCT) system. Shear waves were generated using a piezoelectric transducer transmitting sine-wave bursts of 400 μs duration, applying acoustic radiation force (ARF) to inhomogeneous phantoms and carotid artery samples, synchronized with a swept-source OCT (SS-OCT) imaging system. The phantoms were composed of gelatin and titanium dioxide whereas the carotid artery samples were embedded in gel. Differential OCT phase maps, measured with and without the ARF, detected the microscopic displacement generated by shear wave propagation in these phantoms and samples of different stiffness. We present the technique for calculating tissue mechanical properties by propagating shear waves in inhomogeneous tissue equivalent phantoms and carotid artery samples using the ARF of an ultrasound transducer, and measuring the shear wave speed and its associated properties in the different layers with OCT phase maps. This method lays the foundation for future in-vitro and in-vivo studies of mechanical property measurements of biological tissues such as vascular tissues, where normal and pathological structures may exhibit significant contrast in the shear modulus.OCIS codes: (170.4500) Optical coherence tomography, (170.6935) Tissue characterization     

Assessment of Structural Heterogeneity and Viscosity in the Cervix Using Shear Wave Elasticity Imaging: Initial Results from a Rhesus Macaque Model

Shear wave elasticity imaging has shown promise in evaluation of the pregnant cervix. Changes in shear wave group velocity have been attributed exclusively to changes in stiffness. This assumes homogeneity within the region of interest and purely elastic tissue behavior. However, the cervix is structurally/microstructurally heterogeneous and viscoelastic. We therefore developed strategies to investigate these complex tissue properties. Shear wave elasticity imaging was performed ex vivo on 14 unripened and 13 misoprostol-ripened cervix specimens from rhesus macaques. After tests of significant and uniform shear wave displacement, as well as reliability of estimates, group velocity decreased significantly from the distal (vaginal) to proximal (uterine) end of unripened, but not ripened, specimens. Viscosity was quantified by the slope of the phase velocity versus frequency. Dispersion was observed in both groups (median: 5.5 m/s/kHz, interquartile range: 1.5–12.0 m/s/kHz), also decreasing toward the proximal cervix. This work suggests that comprehensive assessment of complex tissues such as cervix requires consideration of structural heterogeneity and viscosity.     

Integration of crawling waves in an ultrasound imaging system. Part 2: signal processing and applications

This paper introduces methods to generate crawling wave interference patterns from the displacement fields generated from radiation force pushes on a GE Logiq 9 scanner. The same transducer and system provides both the pushing pulses to generate the shear waves and the tracking pulses to measure the displacements. Acoustic power and system limitations result in largely impulsive displacement fields. Measured displacements from pushes on either side of a region-of-interest (ROI) are used to calculate continuously varying interference patterns. This technique is explained along with a brief discussion of the conventional mechanical source-driven crawling waves for comparison. We demonstrate the method on three example cases: a gelatin-based phantom with a cylindrical inclusion, an oil-gelatin phantom and mouse livers. The oil-gelatin phantom and the mouse livers demonstrate not only shear speed estimation, but the frequency dependence of the shear wave speeds.     

Ultrasound Dynamic Micro-Elastography Applied to the Viscoelastic Characterization of Soft Tissues and Arterial Walls

Quantitative noninvasive methods that provide in vivo assessment of mechanical characterization of living tissues, organs and artery walls are of interest because information on their viscoelastic properties in the presence of disease can affect diagnosis and treatment options. This article proposes the dynamic micro-elastography (DME) method to characterize viscoelasticity of small homogeneous soft tissues, as well as the adaptation of the method for vascular applications [vascular dynamic micro-elastography (VDME)]. The technique is based on the generation of relatively high-frequency (240–1100 Hz) monochromatic or transient plane shear waves within the medium and the tracking of these waves from radio-frequency (RF) echoes acquired at 25 MHz with an ultrasound biomicroscope (Vevo 770, Visualsonics). By employing a dedicated shear wave gated strategy during signal acquisition, postprocessed RF sequences could achieve a very high frame rate (16,000 images per s). The proposed technique successfully reconstructed shear wave displacement maps at very high axial (60 μm) and lateral (250 μm) spatial resolutions for motions as low as a few μm. An inverse problem formulated as a least-square minimization, involving analytical simulations (for homogenous and vascular geometries) and experimental measurements were performed to retrieve storage (G′) and loss (G″) moduli as a function of the shearing frequency. Viscoelasticity measurements of agar-gelatin materials and of a small rat liver were proven feasible. Results on a very thin wall (3 mm thickness) mimicking artery enabled to validate the feasibility and the reliability of the vascular inverse problem formulation. Subsequently, the G′ and G″ of a porcine aorta showed that both parameters are strongly dependent on frequency, suggesting that the vascular wall is mechanically governed by complex viscoelastic laws. (E-mail: guy.cloutier@umontreal.ca)     

Elasticity Estimates from Images of Crawling Waves Generated by Miniature Surface Sources

We describe a surface-based approach to the generation of shear wave interference patterns, called crawling waves (CrW), within a medium and derive local estimates of biomechanical properties of tissue. In previous experiments, elongated bars operating as vibration sources were used to generate CrW propagation in samples. In the present study, however, a pair of miniature circular vibration sources was applied to the overlying skin to generate the CrW within the medium. The shape and position of the miniature sources make this configuration more applicable for in vivo implementation. A modified ultrasound imaging system is used to display the CrW propagation. A shear speed mapping algorithm is developed using a detailed analysis of the CrW. The proposed setup is applied to several biomaterials including a homogeneous phantom, an inhomogeneous phantom and an ex vivo human liver. The data are analyzed using the mapping algorithm to reveal the biomechanical properties of the biomaterials.     

Comprehensive Viscoelastic Characterization of Tissues and the Inter-relationship of Shear Wave (Group and Phase) Velocity,Attenuation and Dispersion

We report shear wave phase and group velocity, dispersion and attenuation in oil-in-gelatin viscoelastic phantoms and in vivo liver data. Moreover, we measured the power law coefficient from each dispersion curve and used it, together with the shear wave velocity, to calculate an approximate value for attenuation that agrees with independent attenuation measurements. Results in phantoms exhibit good agreement for all parameters with respect to independent mechanical measurements. For in vivo data, the livers of 20 patients were scanned. Results were compared with pathology scores obtained from liver biopsies. Across these cases, increases in shear wave dispersion and attenuation were related to increased steatosis score. It was found that shear wave dispersion and attenuation are experimentally linked, consistent with simple predictions based on the rheology of tissues, and can be used individually or jointly to assess tissue viscosity. Thus, this study indicates the possible utility of using shear wave dispersion and attenuation to non-invasively and quantitatively assess steatosis.     

Quantifying hepatic shear modulus in vivo using acoustic radiation force

The speed at which shear waves propagate in tissue can be used to quantify the shear modulus of the tissue. As many groups have shown, shear waves can be generated within tissues using focused, impulsive, acoustic radiation force excitations, and the resulting displacement response can be ultrasonically tracked through time. The goals of the work herein are twofold: (i) to develop and validate an algorithm to quantify shear wave speed from radiation force-induced, ultrasonically-detected displacement data that is robust in the presence of poor displacement signal-to-noise ratio and (ii) to apply this algorithm to in vivo datasets acquired in human volunteers to demonstrate the clinical feasibility of using this method to quantify the shear modulus of liver tissue in longitudinal studies. The ultimate clinical application of this work is noninvasive quantification of liver stiffness in the setting of fibrosis and steatosis. In the proposed algorithm, time-to-peak displacement data in response to impulsive acoustic radiation force outside the region of excitation are used to characterize the shear wave speed of a material, which is used to reconstruct the material's shear modulus. The algorithm is developed and validated using finite element method simulations. By using this algorithm on simulated displacement fields, reconstructions for materials with shear moduli (mu) ranging from 1.3-5 kPa are accurate to within 0.3 kPa, whereas stiffer shear moduli ranging from 10-16 kPa are accurate to within 1.0 kPa. Ultrasonically tracking the displacement data, which introduces jitter in the displacement estimates, does not impede the use of this algorithm to reconstruct accurate shear moduli. By using in vivo data acquired intercostally in 20 volunteers with body mass indices ranging from normal to obese, liver shear moduli have been reconstructed between 0.9 and 3.0 kPa, with an average precision of +/-0.4 kPa. These reconstructed liver moduli are consistent with those reported in the literature (mu = 0.75-2.5 kPa) with a similar precision (+/-0.3 kPa). Repeated intercostal liver shear modulus reconstructions were performed on nine different days in two volunteers over a 105-day period, yielding an average shear modulus of 1.9 +/- 0.50 kPa (1.3-2.5 kPa) in the first volunteer and 1.8 +/- 0.4 kPa (1.1-3.0 kPa) in the second volunteer. The simulation and in vivo data to date demonstrate that this method is capable of generating accurate and repeatable liver stiffness measurements and appears promising as a clinical tool for quantifying liver stiffness.