The clinical use of elastography for monitoring fibrosis progression is challenged by the subtle changes in liver stiffness associated with early-stage fibrosis and the comparatively large variance in stiffness estimates provided by elastography. Single-tracking-location (STL) shear wave elasticity imaging (SWEI) is an ultrasound elastography technique previously found to provide improved estimate precision compared with multiple-tracking-location (MTL) SWEI. Because of the improved precision, it is reasonable to expect that STL-SWEI would provide improved ability to differentiate liver fibrosis stage compared with MTL-SWEI. However, this expectation has not been previously challenged rigorously. In this work, the performance of STL- and MTL-SWEI in the setting of a rat model of liver fibrosis is characterized, and the advantages of STL-SWEI in staging fibrosis are explored. The purpose of this study was to determine what advantages, if any, arise from using STL-SWEI instead of MTL-SWEI in the characterization of fibrotic liver. Thus, the ability of STL-SWEI to differentiate livers at various METAVIR fibrosis scores, for ex vivo postmortem measurements, is explored. In addition, we examined the effect of the common confounding factor of fluid versus solid boundary conditions in SWEI experiments. Sprague-Dawley rats were treated with carbon tetrachloride over several weeks to produce liver disease of varying severity. STL and MTL stiffness measurements were performed ex vivo and compared with the METAVIR scores from histological analysis and the duration of treatment. A strong association was observed between liver stiffness and weeks of treatment with the liver toxin carbon tetrachloride. Direct comparison of STL- and MTL-SWEI measurements revealed no significant difference in ability to differentiate fibrosis stages based on SWEI mean values. However, image interquartile range was greatly improved in the case of STL-SWEI, compared with MTL-SWEI, at small beam spacing.
Single tracking location (STL) shear wave elasticity imaging (SWEI) is a method for detecting elastic differences between tissues. It has the advantage of intrinsic speckle bias suppression compared with multiple tracking location variants of SWEI. However, the assumption of a linear model leads to an overestimation of the shear modulus in viscoelastic media. A new reconstruction technique denoted single tracking location viscosity estimation (STL-VE) is introduced to correct for this overestimation. This technique utilizes the same raw data generated in STL-SWEI imaging. Here, the STL-VE technique is developed by way of a maximum likelihood estimation for general viscoelastic materials. The method is then implemented for the particular case of the Kelvin-Voigt Model. Using simulation data, the STL-VE technique is demonstrated and the performance of the estimator is characterized. Finally, the STL-VE method is used to estimate the viscoelastic parameters of ex vivo bovine liver. We find good agreement between the STL-VE results and the simulation parameters as well as between the liver shear wave data and the modeled data fit.
In ultrasound-based elastography methods, the estimation of shear wave velocity typically involves the tracking of speckle motion due to an applied force. The errors in the estimates of tissue displacement, and thus shear wave velocity, are generally attributed to electronic noise and decorrelation due to physical processes. We present our preliminary findings on another source of error, namely, speckle-induced bias in phase estimation. We find that methods that involve tracking in a single location, as opposed to multiple locations, are less sensitive to this source of error since the measurement is differential in nature and cancels out speckle-induced phase errors.
Spatially modulated ultrasound radiation force (SMURF) imaging is an elastographic technique that involves generating a radiation force beam with a lateral intensity variation of a defined spatial frequency. This results in a shear wave of known wavelength. By using the displacements induced by the shear wave and standard Doppler or speckle-tracking methods, the shear wave frequency, and thus material shear modulus, is estimated. In addition to generating a pushing beam pattern with a specified lateral intensity variation, it is generally desirable to induce larger displacements so that the displacement data signal-to-noise ratio is higher. We provide an analysis of two beam forming methods for generating SMURF in an elastic material: the focal Fraunhofer and intersecting plane wave methods. Both techniques generate beams with a defined spatial frequency. However, as a result of the trade-offs associated with each technique, the peak acoustic intensity outputs in the region of interest differs for the same combinations of parameters (e.g., the focal depth, the width of the area of interest, and ultrasonic attenuation coefficient). Assuming limited transducer drive voltage, we provide a decision plot to determine which of the two techniques yields the greater pushing force for a specific configuration.
The application of Spatially-Modulated Ultrasound Radiation Force (SMURF) to shear modulus imaging is demonstrated in tissue-mimicking phantoms and porcine liver. Scanning and data acquisition was performed with a Siemens Antares ultrasound scanner and VF7-3 linear array operating at 4.21 MHz. Modulus estimates in uniform phantoms of Zerdine with shear moduli of 5.1 and 12.4 kPa exhibited standard deviations within 6% of the mean value. Zerdine spheres 1 cm in diameter (nominally 2.7, 4.7 and 15 kPa) in a 8 kPa (nominal) background are clearly resolved. Cross sectional images of a soft conical inclusion in a gelatin-based phantom indicate a spatial resolution of approximately 2.5 mm. Images of the shear modulus of an ex-vivo sample of porcine liver tissue show an average value of 3 kPa. A stiff lesion induced with 0.5 mL of 10% glutaraldehyde is clearly visible as a region of shear modulus in excess of 10 kPa. A modulus gradient associated with the diffusion of the glutaraldehyde is visible. Two pulse sequences were examined, differing only in the timing of the beams used to generate the shear waves. Details of the beam sequences and subsequent signal processing are presented.
A validation study of the Spatially Modulated Ultrasound Radiation Force (SMURF) method for shear modulus estimation is presented. SMURF estimates of uniform gelatin and Zerdine™ phantoms covering a modulus range of 2 to 18 kPa are compared with results obtained by unconfined mechanical compression and sonoelastography. The results show agreement within the measurement uncertainties over the range indicated for all three methods. Repeatability and variation on the order of 5% of the phantom modulus are found for observations made at a single point within the phantom. Averaging of modulus estimates from several adjacent scan lines further decreases the variation. By using multiple radiation force peaks to induce a shear wave of known wavelength and measure the frequency of the wave, SMURF obtains modulus estimates from tracking data acquired along a single A-line. This is significant, as speckle can bias the measured phase of the shear wave. SMURF is shown to be insensitive to a constant phase error in the shear wave measurement. This results in greatly reduced correlated noise in the modulus estimates, in contrast with methods which track at multiple locations and do not cancel phase errors.
Spatially Modulated Ultrasound Radiation Force (SMURF) imaging is an Elastography technique based on estimating the shear modulus of an elastic material . SMURF determines shear modulus through measurement of the frequency of shear waves of known wavelength propagating in a medium of unknown modulus. Shear modulus is then computed using the relationship G = (¿f)2¿. The spatial frequency k of the force variation is equal to the desired spatial frequency of the shear wave, that is, k = 2¿/¿. Because acoustic radiation force used to create the shear waves is proportional to intensity, generation of this spatially varying force is a matter of determining how to generate an equivalently varying ultrasound intensity field. Presented in this study is the Focal Fraunhofer method, which is one of the techniques that can be used to create the desired beam intensity pattern within a region of interest. To create a push that results in discernible displacements while minimizing tissue heating in the near field, we investigate the use of both a linear and a multi-row 1.5D array. A 1.5D array allows for more aggressive focusing in the elevation direction and thus a greater intensity in the region of interest. The efficacy of both configurations is analyzed based on the ability to generate beams of the desired well-defined spatial wavelength at various focal depths, the ability to localize the pushing beam to the region of interest and the ability to maximize the depth-of-field.
Spatially modulated ultrasound radiation force (SMURF) [S. McAleavey et al., Ultrason. Imag. 29, 87–104, (2007)] is a novel method for ultrasonic estimation of the low-frequency shear modulus properties of elastic media. In this approach, radiation force with a known lateral magnitude variation is applied impulsively within a region of interest using short (∼30 μs) bursts of ultrasound. The spatial frequency k of the radiation force intensity variation is selectable and determined through beamforming. Application of the radiation force impulse gives rise to a low-frequency (500–2000 Hz) shear wave. The temporal frequency ω of this wave is measured using Doppler ultrasound methods. The modulus is estimated from the relationship G=ρ(ωk)2, where ρ is the material density. To validate this method, the moduli of five samples of Zerdine (CIRS, Incorporated), an ultrasonically tissue-equivalent elastic material, were measured using conventional unconfined cyclic compression and SMURF implemented on a Siemens Antares scanner. The samples were cylindrical with diam 54 mm and height 25 mm. The shear modulus of the samples ranged from 2.5–35 kPa. For all samples, the two methods agreed to within the estimated variation. An intrasample variation of 8% was observed for SMURF in the (assumed uniform) samples. [Work supported by NIH/NIBIB.]