Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. In current shear wave elasticity imaging methods typically only shear wave speed is measured and rheological models, e.g., Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for tissue mechanical properties such as the shear viscoelastic complex modulus. This paper presents a method to quantify viscoelastic material properties in a model-independent way by estimating the complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. This radiation force induced creep (RFIC) method uses a conversion formula that is the analytic solution of a constitutive equation. The proposed method in combination with Shearwave Dispersion Ultrasound Vibrometry (SDUV) is used to measure the complex modulus so that knowledge of the applied radiation force magnitude is not necessary. The conversion formula is shown to be sensitive to sampling frequency and the first reliable measure in time according to numerical simulations using the Kelvin-Voigt model creep strain and compliance. Representative model-free shear complex moduli from homogeneous tissue mimicking phantoms and one excised swine kidney were obtained. This work proposes a novel model-free ultrasound-based elasticity method that does not require a rheological model with associated fitting requirements.

Shearwave Dispersion Ultrasound Vibrometry (SDUV) is used to quantify both tissue shear elasticity and shear viscosity by evaluating dispersion of shear wave propagation speed over a certain bandwidth (50–500 Hz). The motivation for developing elasticity imaging techniques is based on the possibility of diagnosing disease process. However, it is important to study the mechanical properties of healthy tissues; such data can enhance clinical knowledge and improve understanding of the mechanical properties of tissue. The purpose of this study is to evaluate the feasibility of SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity on healthy swine kidney. A total of eight excised kidneys from female pigs were used in these in vitro experiments, and a battery of different tests were performed to gain insight on the material properties of the renal cortex. From these eight kidneys, the overall renal cortex elasticity and viscosity was 1.81 ± 0.17 kPa and 1.48 ± 0.49 Pa·s, respectively. In an analysis of the material properties over time after excision, there was not a statistically significant difference in shear elasticity over a 24 hour period, but a statistically significant difference in shear viscosity was found. Homogeneity of the renal cortex was examined and it was found that shear elasticity and shear viscosity were statistically different within a kidney, suggesting global tissue inhomogeneity. More than 30% increases in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Lastly, it was found that the renal cortex is rather anisotropic. Two values for shear elasticity and shear viscosity were measured depending on shear wave propagation direction. These various tests elucidated different aspects of the material properties and the structure of the ex vivo renal cortex.

Measurement of tissue elasticity has emerged as an important advance in medical imaging and tissue characterization. However, soft tissue is inherently a viscoelastic material. One way to characterize the viscoelastic material properties of a material is to measure shear wave propagation velocities within the material at different frequencies and use the dispersion of the velocities, or variation with frequency, to solve for the material properties. Shearwave Dispersion Ultrasound Vibrometry (SDUV) is an ultrasound-based technique that uses this feature to characterize the viscoelastic nature of soft tissue. This method has been used to measure the shear elasticity and viscosity in various types of soft tissues including skeletal muscle, cardiac muscle, liver, kidney, prostate, and arterial vessels. This versatile technique provides measurements of viscoelastic material properties with high spatial and temporal resolution, which can be used for assessing these properties in normal and pathologic tissues. The goals of this paper are to 1) give an overview of viscoelasticity and shear wave velocity dispersion, 2) provide a history of the development of the SDUV method, and 3) survey applications for SDUV that have been previously reported.

Measurement of shear wave propagation speed has important clinical applications because it is related to tissue stiffness and health state. Shear waves can be generated in tissues by the radiation force of a focused ultrasound beam (push beam). Shear wave speed can be measured by tracking its propagation laterally from the push beam focus using the time-of-flight principle. This study shows that shear wave speed measurements with such methods can be transducer, depth, and lateral tracking range dependent. Three homogeneous phantoms with different stiffness were studied using curvilinear and linear array transducer. Shear wave speed measurements were made at different depths, using different aperture sizes for push, and at different lateral distance ranges from the push beam. The curvilinear transducer shows a relatively large measurement bias that is depth dependent. The possible causes of the bias and options for correction are discussed. These bias errors must be taken into account to provide accurate and precise time-of-flight shear wave speed measurements for clinical use.

From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.

In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.

Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.

In recent years, several new techniques based on the radiation force of ultrasound have been developed. Vibro-acoustography is a speckle-free ultrasound based imaging modality that can visualize normal and abnormal soft tissue through mapping the acoustic response of the object to a harmonic radiation force induced by ultrasound. In vibro-acoustography, the ultrasound energy is converted from high ultrasound frequencies to a low acoustic frequency (acoustic emission) that is often two orders of magnitude smaller than the ultrasound frequency. The acoustic emission is normally detected by a hydrophone. In medical imaging, vibroacoustography has been tested on breast, prostate, arteries, liver, and thyroid. These studies have shown that vibro-acoustic data can be used for quantitative evaluation of elastic properties. This paper presents an overview of vibro-acoustography and its applications in the areas of biomedicine.

Characterization of the viscoelastic material properties of soft tissue has become an important area of research over the last two decades. Our group has been investigating the feasibility of using Shearwave Dispersion Ultrasound Vibrometry (SDUV) method to excite Lamb waves in organs with plate-like geometry to estimate the viscoelasticity of the medium of interest. The use of Lamb wave Dispersion Ultrasound Vibrometry (LDUV) to quantify mechanical properties of viscoelastic solids has previously been reported. Two organs, the heart wall and the spleen, can be readily modeled using plate-like geometries. The elasticity of these two organs is important because they change in pathological conditions. Diastolic dysfunction is the inability of the left ventricle (LV) of the heart to supply sufficient stroke volumes into the systemic circulation and is accompanied by the loss of compliance and stiffening of the LV myocardium. It has been shown that there is a correlation between high splenic stiffness in patients with chronic liver disease and strong correlation between spleen and liver stiffness. Here, we investigate the use of the SDUV method to quantify viscoelasticity of the LV free-wall myocardium and spleen by exciting Rayleigh waves on the organ’s surface and measuring the wave dispersion (change of wave velocity as a function of frequency) in the frequency range 40–500 Hz. An equation for Rayleigh wave dispersion due to cylindrical excitation was derived by modeling the excised myocardium and spleen with a homogenous Voigt material plate immersed in a nonviscous fluid. Boundary conditions and wave potential functions were solved for the surface wave velocity. Analytical and experimental convergence between the Lamb and Rayleigh waves is reported in a finite element model of a plate in a fluid of similar density, gelatin plate and excised porcine spleen and left-ventricular free-wall myocardium.

Vibro-acoustography is an ultrasound based imaging modality that can visualize normal and abnormal soft tissue through mapping the acoustic response of the object to a harmonic radiation force at frequency Δf induced by focused ultrasound. In this method, the ultrasound energy is converted from high ultrasound frequencies to a low acoustic frequency (acoustic emission) that is often two orders of magnitude smaller than the ultrasound frequency. The acoustic emission is normally detected by a hydrophone. Depending on the setup, this low frequency sound may reverberate by object boundaries or other structures present in the acoustic paths before it reaches the hydrophone. This effect produces an artifact in the image in the form of gradual variations in image intensity that may compromise image quality. The use of tonebursts with finite length yields acoustic emission at Δf and at sidebands centered about Δf. Multiple images are formed by selectively applying bandpass filters on the acoustic emission at Δf and the associated sidebands. The data at these multiple frequencies are compounded through both coherent and incoherent processes to reduce the acoustic emission reverberation artifacts. Experimental results from a urethane breast phantom are described. The coherent and incoherent compounding of multifrequency data show, both qualitatively and quantitatively, the efficacy of this reverberation reduction method. This paper presents theory describing the physical origin of this artifact and use of image data created using multifrequency vibro-acoustography for reducing reverberation artifacts.

Arterial elasticity has gained importance in the past decades because it has been shown to be an independent predictor of cardiovascular diseases. Several in vivo and ex vivo techniques have been developed to characterize the elastic properties of vessels. In vivo techniques tend to ignore the anisotropy of the mechanical properties in the vessel wall, and therefore, fail to characterize elasticity in different directions. Ex vivo techniques, have focused their efforts in studying the mechanical properties in different axes. In this paper, we present a technique that uses piezoelectric elements to measure the elasticity of soft tubes and excised arteries in two directions while maintaining the natural structure of these vessels. This technique uses sonometry data from piezoelectric elements to measure the strain in the longitudinal and circumferential directions while the tubes/arteries are being pressurized. We conducted experiments on urethane tubes to evaluate the technique and compared the experimental results with mechanical testing done on the materials used for making the tubes. We then performed sonometry experiments on excised pig carotid arteries assuming that they are transversely isotropic materials. To evaluate the sensitivity of this technique to changes in the material properties, we changed the temperature of the saline bath in which the arteries were immersed. The calculated Young’s modulus from sonometry experiments for the urethane tubes and the mechanical testing values showed good agreement, deviating no more than 13.1%. The elasticity values from the excised arteries and the behavior with the temperature changed agreed with previous work done in similar arteries. Therefore, we propose this technique for nondestructive testing of the biaxial properties of soft materials tubes and excised arteries in their natural physiological shape.

Tissue mechanical properties such as elasticity are linked to tissue pathology state. Several groups have proposed shear wave propagation speed to quantify tissue mechanical properties. It is well known that biological tissues are viscoelastic materials; therefore velocity dispersion resulting from material viscoelasticity is expected. A method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) can be used to quantify tissue viscoelasticity by measuring dispersion of shear wave propagation speed. However, there is not a gold standard method for validation. In this study we present an independent validation method of shear elastic modulus estimation by SDUV in 3 gelatin phantoms of differing stiffness. In addition, the indentation measurements are compared to estimates of elasticity derived from shear wave group velocities. The shear elastic moduli from indentation were 1.16, 3.40 and 5.6 kPa for a 7, 10 and 15% gelatin phantom respectively. SDUV measurements were 1.61, 3.57 and 5.37 kPa for the gelatin phantoms respectively. Shear elastic moduli derived from shear wave group velocities were 1.78, 5.2 and 7.18 kPa for the gelatin phantoms respectively. The shear elastic modulus estimated from the SDUV, matched the elastic modulus measured by indentation. On the other hand, shear elastic modulus estimated by group velocity did not agree with indentation test estimations. These results suggest that shear elastic modulus estimation by group velocity will be bias when the medium being investigated is dispersive. Therefore a rheological model should be used in order to estimate mechanical properties of viscoelastic materials.

Vibro-acoustography is an ultrasound-based imaging modality that uses two ultrasound beams of slightly different frequencies to produce images based on the acoustic response due to harmonic ultrasound radiation force excitation at the difference frequency between the two ultrasound frequencies. Vibro-acoustography has demonstrated feasibility and usefulness in imaging of breast and prostate tissue. However, previous studies have been performed either in controlled water tank settings or a prototype breast scanner equipped with a water tank. In order to make vibro-acoustography more accessible and relevant to clinical use, we report here on the implementation of vibro-acoustography on a General Electric Vivid 7 ultrasound scanner. In this paper, we will describe software and hardware modifications that were performed to make vibro-acoustography functional on this system. We will discuss aperture definition for the two ultrasound beams and beamforming using a linear array transducer. Experimental results from beam measurements and phantom imaging studies will be shown. The implementation of vibro-acoustography provides a step towards clinical translation of this imaging modality for applications in various organs including breast, prostate, thyroid, kidney, and liver.

Diastolic dysfunction is the inability of the left ventricle to supply sufficient stroke volumes under normal physiological conditions and is often accompanied by stiffening of the left-ventricular myocardium. A noninvasive technique capable of quantifying viscoelasticity of the myocardium would be beneficial in clinical settings.

Our group has been investigating the use of Shearwave Dispersion Ultrasound Vibrometry (SDUV), a noninvasive ultrasound based method for quantifying viscoelasticity of soft tissues. The primary motive of this study is the design and testing of viscoelastic materials suitable for validation of the Lamb wave Dispersion Ultrasound Vibrometry (LDUV), an SDUV-based technique for measuring viscoelasticity of tissues with plate-like geometry. We report the results of quantifying viscoelasticity of urethane rubber and gelatin samples using LDUV and an embedded sphere method. The LDUV method was used to excite antisymmetric Lamb waves and measure the dispersion in urethane rubber and gelatin plates. An antisymmetric Lamb wave model was fitted to the wave speed dispersion data to estimate elasticity and viscosity of the materials. A finite element model of a viscoelastic plate submerged in water was used to study the appropriateness of the Lamb wave dispersion equations. An embedded sphere method was used as an independent measurement of the viscoelasticity of the urethane rubber and gelatin. The FEM dispersion data were in excellent agreement with the theoretical predictions. Viscoelasticity of the urethane rubber and gelatin obtained using the LDUV and embedded sphere methods agreed within one standard deviation. LDUV studies on excised porcine myocardium sample were performed to investigate the feasibility of the approach in preparation for open-chest in vivo studies. The results suggest that the LDUV technique can be used to quantify mechanical properties of soft tissues with a plate-like geometry.

Vibro-acoustography (VA) is an imaging method that forms a two-dimensional (2-D) image by moving two cofocused ultrasound beams with slightly different frequencies over the object in a C-scan format and recording acoustic emission from the focal region at the difference frequency. This article studies tissue heating due to a VA scan using a concentric confocal transducer. The three-dimensional (3-D) ultrasound intensity field calculated by Field II is used with the bio-heat equation to estimate tissue heating due to ultrasound absorption. Results calculated with thermal conduction and with blood perfusion, with conduction and without perfusion and without conduction and without perfusion are compared. Maximum heating due to ultrasound absorption occurs in the transducer’s near-field and maximum temperature rise in soft tissue during a single VA scan is below 0.05°C for all three attenuation coefficients evaluated: 0.3, 0.5 and 0.7 dB/cm/MHz. Transducer self-heating during a single VA scan measured by a thermocouple is less than 0.27°C.

Characterization of tissue elasticity (stiffness) and viscosity has important medical applications because these properties are closely related to pathological changes. Quantitative measurement is more suitable than qualitative measurement (i.e., mapping with a relative scale) of tissue viscoelasticity for diagnosis of diffuse diseases where abnormality is not confined to a local region and there is no normal background tissue to provide contrast. Shearwave dispersion ultrasound vibrometry (SDUV) uses shear wave propagation speed measured in tissue at multiple frequencies (typically in the range of hundreds of Hertz) to solve quantitatively for both tissue elasticity and viscosity. A shear wave is stimulated within the tissue by an ultrasound push beam and monitored by a separate ultrasound detect beam. The phase difference of the shear wave between 2 locations along its propagation path is used to calculate shear wave speed within the tissue. In vitro SDUV measurements along and across bovine striated muscle fibers show results of tissue elasticity and viscosity close to literature values. An intermittent pulse sequence is developed to allow one array transducer for both push and detect function. Feasibility of this pulse sequence is demonstrated by in vivo SDUV measurements in swine liver using a dual transducer prototype simulating the operation of a single array transducer.

Shear wave velocity measurements are used in elasticity imaging to find the shear elasticity and viscosity of tissue. A technique called shear wave dispersion ultrasound vibrometry (SDUV) has been introduced to use the dispersive nature of shear wave velocity to locally estimate the material properties of tissue. Shear waves are created using a multifrequency ultrasound radiation force, and the propagating shear waves are measured a few millimeters away from the excitation point. The shear wave velocity is measured using a repetitive pulse-echo method and Kalman filtering to find the phase of the harmonic shear wave at 2 different locations. A viscoelastic Voigt model and the shear wave velocity measurements at different frequencies are used to find the shear elasticity (μ1) and viscosity (μ2) of the tissue. The purpose of this paper is to report the accuracy of the SDUV method over a range of different values of μ1 and μ2.

A motion detection model of a vibrating scattering medium was used to analyze measurement errors of vibration phase in a scattering medium. To assess the accuracy of the SDUV method, we modeled the effects of phase errors on estimates of shear wave velocity and material properties while varying parameters such as shear stiffness and viscosity, shear wave amplitude, the distance between shear wave measurements (Δr), signal-to-noise ratio (SNR) of the ultrasound pulse-echo method, and the frequency range of the measurements. We performed an experiment in a section of porcine muscle to evaluate variation of the aforementioned parameters on the estimated shear wave velocity and material property measurements and to validate the error prediction model.

The model showed that errors in the shear wave velocity and material property estimates were minimized by maximizing shear wave amplitude, pulse-echo SNR, Δr, and the bandwidth used for shear wave measurements. The experimental model showed optimum performance could be obtained for Δr = 3-6 mm, SNR ≥35 dB, with a frequency range of 100 to 600 Hz, and with a shear wave amplitude on the order of a few microns down to 0.5 μm. The model provides a basis to explore different parameters related to implementation of the SDUV method. The experiment confirmed conclusions made by the model, and the results can be used for optimization of SDUV.

Elasticity imaging is an emerging medical imaging modality that seeks to map the spatial distribution of tissue stiffness. Ultrasound radiation force excitation and motion tracking using pulse-echo ultrasound have been used in numerous methods. Dynamic radiation force is used in vibrometry to cause an object or tissue to vibrate, and the vibration amplitude and phase can be measured with exceptional accuracy. This paper presents a model that simulates harmonic motion detection in a vibrating scattering medium incorporating 3-D beam shapes for radiation force excitation and motion tracking. A parameterized analysis using this model provides a platform to optimize motion detection for vibrometry applications in tissue. An experimental method that produces a multifrequency radiation force is also presented. Experimental harmonic motion detection of simultaneous multifrequency vibration is demonstrated using a single transducer. This method can accurately detect motion with displacement amplitude as low as 100 to 200 nm in bovine muscle. Vibration phase can be measured within 10° or less. The experimental results validate the conclusions observed from the model and show multifrequency vibration induction and measurements can be performed simultaneously.

Objective

Vibroacoustography allows imaging of objects on the basis of their acoustic signal emitted during low-frequency (kHz) vibrations produced by 2 intersecting ultrasound beams at slightly different frequencies. This study tested the feasibility of using vibroacoustography to distinguish between normal and calcified femoral arteries in a pig model.

Materials and Methods

Thirteen normal porcine femoral arteries, 7 with experimentally induced arterial calcifications, and 1 control artery injected with saline only were scanned in vivo. Images were obtained at 45 kHz using a 3 MHz confocal transducer. The acoustic emission signal was detected with a hydrophone placed on the animal’s limb. Images were reconstructed on the basis of the amplitude of the acoustic emission signal. Vessel patency, vessel dimensions, and the extent of calcified plaques were confirmed in vivo by angiography and conventional ultrasound. Excised arteries were reexamined with vibroacoustography, X-ray radiography, and histology.

Results

In vivo, vibroacoustography produced high-resolution, speckle-free images with a high level of anatomic detail. Measurements of femoral artery diameter were similar by vibroacoustography and conventional ultrasound (mean difference ± SD, 0.1 ± 0.4 mm). Calcified plaque area measured by different methods was comparable (vibroacoustography, in vivo: 1.0 ± 0.9 cm2; vibroacoustography in vitro: 1.1 ± 0.6 cm2; X-ray radiography: 0.9 ± 0.6 cm2). The reproducibility of measurements was high. Sensitivity and specificity for detecting calcifications were 100% and 86%, respectively, and positive and negative predictive values were 77% and 100%, respectively.

Conclusions

Vibroacoustography provides accurate and reproducible measurements of femoral arteries and vascular calcifications in living animals.