Attenuation Measuring Ultrasound Shearwave Elastography as a Method for Evaluating Pancreatic Viscoelasticity.

Pancreatic cancer is the fourth most common cause of cancer-related fatalities as there are a limited number of tools to diagnose this disease in its early stages. Pancreatitis is characterized as an inflammation of the pancreatic tissue due to an excess amount of pancreatic enzymes remaining in the organ. Both of these diseases result in a stiffening of the tissue which makes them suitable for the use of elastography techniques as a diagnostic method. However, these methods typically assume that the tissue is purely elastic when biological tissue is inherently viscoelastic. The attenuation measuring ultrasound shear elastography (AMUSE) method, which measures both attenuation and shear wave velocity was used to characterize the viscoelasticity of pancreatic tissue. This method was tested in ex vivo normal porcine samples that were also stiffened in formalin and in vivo by conducting studies in healthy human subjects. Ex vivo testing showed ranges of phase velocity, group velocity, and phase attenuation values of 1.05 - 1.33 m/s, 0.83 - 1.12 m/s, and 183 - 210 Np/m. After immersing the ex vivo tissue in formalin there was a distinguishable difference between normal and stiffened tissue. This study produced percent difference ranges of phase velocity, group velocity, and phase attenuation from 0 to 100 minutes in formalin of 30.0% - 56.5%, 38.2% - 58.6%, and 55.8% - 64.8%, respectively. The ranges of phase velocity, group velocity, and phase attenuation results in human subjects were 1.53 - 1.60 m/s, 1.76 - 1.91 m/s, and 196 - 204 Np/m, respectively. These results were within a similar range reported by other elastography techniques. Further work with the AMUSE method in subjects with pancreatitis and cancer is needed to determine its effectiveness in showing a difference between healthy and diseased tissue in humans.

In Vivo Open- and Closed-chest Measurements of Left-Ventricular Myocardial Viscoelasticity using Lamb wave Dispersion Ultrasound Vibrometry (LDUV): A Feasibility Study.

Diastolic dysfunction causes close to half of congestive heart failures and is associated with increased stiffness in left-ventricular myocardium. A clinical tool capable of measuring viscoelasticity of the myocardium could be beneficial in clinical settings. We used Lamb wave Dispersion Ultrasound Vibrometry (LDUV) for assessing the feasibility of making in vivo non-invasive measurements of myocardial elasticity and viscosity in pigs. In vivo open-chest measurements of myocardial elasticity and viscosity obtained using a Fourier space based analysis of Lamb wave dispersion are reported. The approach was used to perform ECG-gated transthoracic in vivo measurements of group velocity, elasticity and viscosity throughout a single heart cycle. Group velocity, elasticity and viscosity in the frequency range 50-500 Hz increased from diastole to systole, consistent with contraction and relaxation of the myocardium. Systolic group velocity, elasticity and viscosity were 5.0 m/s, 19.1 kPa, 6.8 Pa·s, respectively. In diastole, the measured group velocity, elasticity and viscosity were 1.5 m/s, 5.1 kPa and 3.2 Pa·s, respectively.

Application of Acoustoelasticity to Evaluate Nonlinear Modulus in Ex Vivo Kidneys.

Currently, dynamic elastography techniques estimate the linear elastic shear modulus of different body tissues. New methods that investigate other properties of soft tissues such as anisotropy, viscosity, and shear nonlinearity would provide more information about the structure and function of the tissue and might provide a better contrast than tissue stiffness and hence provide more effective diagnostic tools for some diseases. It has previously been shown that shear wave velocity in a medium changes due to an applied stress, a phenomenon called acoustoelasticity (AE). Applying a stress to compress a medium while measuring the shear wave velocity versus strain provides data with which the third-order nonlinear shear modulus can be estimated. To evaluate the feasibility of estimating , we evaluated ten ex vivo porcine kidneys embedded in 10% porcine gelatin to mimic the case of a transplanted kidney. Under assumptions of an elastic incompressible medium for AE measurements, the shear modulus was quantified at each compression level and the applied strain was assessed by measuring the change in the thickness of the kidney cortex. Finally, was calculated by applying the AE theory. Our results demonstrated that it is possible to estimate a nonlinear shear modulus by monitoring the changes in strain and due to kidney deformation. The magnitudes of are higher when the compression is performed progressively and when using a plate attached to the transducer. Nevertheless, the values obtained for are similar to those previously reported in the literature for breast tissue.

Attenuation measuring ultrasound shearwave elastography and in vivo application in post-transplant liver patients.

Ultrasound and magnetic resonance elastography techniques are used to assess mechanical properties of soft tissues. Tissue stiffness is related to various pathologies such as fibrosis, loss of compliance, and cancer. One way to perform elastography is measuring shear wave velocity of propagating waves in tissue induced by intrinsic motion or an external source of vibration, and relating the shear wave velocity to tissue elasticity. All tissues are inherently viscoelastic and ignoring viscosity biases the velocity-based estimates of elasticity and ignores a potentially important parameter of tissue health. We present attenuation measuring ultrasound shearwave elastography (AMUSE), a technique that independently measures both shear wave velocity and attenuation in tissue and therefore allows characterization of viscoelasticity without using a rheological model. The theoretical basis for AMUSE is first derived and validated in finite element simulations. AMUSE is validated against the traditional methods for assessing shear wave velocity (phase gradient) and attenuation (amplitude decay) in tissue mimicking phantoms and excised tissue. The results agreed within one standard deviation. AMUSE was used to measure shear wave velocity and attenuation in 15 transplanted livers in patients with potential acute rejection, and the results were compared with the biopsy findings in a preliminary study. The comparison showed excellent agreement and suggests that AMUSE can be used to separate transplanted livers with acute rejection from livers with no rejection.

Investigation of the effects of myocardial anisotropy for shear wave elastography using impulsive force and harmonic vibration.

The myocardium is known to be an anisotropic medium where the muscle fiber orientation changes through the thickness of the wall. Shear wave elastography methods use propagating waves which are measured by ultrasound or magnetic resonance imaging (MRI) techniques to characterize the mechanical properties of various tissues. Ultrasound- or MR-based methods have been used and the excitation frequency ranges for these various methods cover a large range from 24-500 Hz. Some of the ultrasound-based methods have been shown to be able to estimate the fiber direction. We constructed a model with layers of elastic, transversely isotropic materials that were oriented at different angles to simulate the heart wall in systole and diastole. We investigated the effect of frequency on the wave propagation and the estimation of fiber direction and wave speeds in the different layers of the assembled models. We found that waves propagating at low frequencies such as 30 or 50 Hz showed low sensitivity to the fiber direction but also had substantial bias in estimating the wave speeds in the layers. Using waves with higher frequency content (>200 Hz) allowed for more accurate fiber direction and wave speed estimation. These results have particular relevance for MR- and ultrasound-based elastography applications in the heart.

Use of Shear Wave Ultrasound Vibrometry for Detection of Simulated Esophageal Malignancy in Ex Vivo Porcine Esophagi.

Esophageal cancer is a malignant neoplasm with poor outcomes. Determination of local disease progression is a major determining factor in treatment modality, radiation dose, radiation field and subsequent surgical therapy. Discrimination of true tumor extent is difficult given the similarity of soft tissues of the malignancy compared to non-malignant tissues using current imaging modalities. A possible method to discriminate between these tissues may be to exploit mechanical properties to diagnostic advantage, as malignant tissues tend to be stiffer relative to normal adjacent tissue. Shear waves propagate faster in stiffer tissues relative to softer tissues. This may be measured by using ultrasound based shear wave vibrometry. In this method, acoustic radiation force is used to create a shear wave in the tissue of interest and ultrafast ultrasound imaging is used to track the propagating wave to measure the wave velocity and estimate the shear moduli. In this study we created simulated malignant lesions (1.5 cm length) using radiofrequency ablation in ex vivo esophageal samples with varied progression (partial thickness n = 4, and full thickness n = 5) and used normal regions of the same esophageal specimen as controls. Shear wave vibrometry was used to measure shear wave group velocity and shear wave phase velocity in the ex vivo specimens. These values were used to estimate shear moduli using an elastic shear wave model and elastic and viscoelastic Lamb wave models. Our results show that the group and phase velocities increase due to both full and mucosal ablation, and that discrimination may be provided by higher order analysis using viscoelastic Lamb wave fitting. This technique may have application for determination of extent of early esophageal malignancy and warrants further investigation using in vivo approaches to determine performance compared to current imaging modalities.

Characterization of material properties of soft solid thin layers with acoustic radiation force and wave propagation.

Evaluation of tissue engineering constructs is performed by a series of different tests. In many cases it is important to match the mechanical properties of these constructs to those of native tissues. However, many mechanical testing methods are destructive in nature which increases cost for evaluation because of the need for additional samples reserved for these assessments. A wave propagation method is proposed for characterizing the shear elasticity of thin layers bounded by a rigid substrate and fluid-loading, similar to the configuration for many tissue engineering applications. An analytic wave propagation model was derived for this configuration and compared against finite element model simulations and numerical solutions from the software package Disperse. The results from the different models found very good agreement. Experiments were performed in tissue-mimicking gelatin phantoms with thicknesses of 1 and 4 mm and found that the wave propagation method could resolve the shear modulus with very good accuracy, no more than 4.10% error. This method could be used in tissue engineering applications to monitor tissue engineering construct maturation with a nondestructive wave propagation method to evaluate the shear modulus of a material.

Shear wave vibrometry evaluation in transverse isotropic tissue mimicking phantoms and skeletal muscle.

Ultrasound radiation force-based methods can quantitatively evaluate tissue viscoelastic material properties. One of the limitations of the current methods is neglecting the inherent anisotropy nature of certain tissues. To explore the phenomenon of anisotropy in a laboratory setting, we created two phantom designs incorporating fibrous and fishing line material with preferential orientations. Four phantoms were made in a cube-shaped mold; both designs were arranged in multiple layers and embedded in porcine gelatin using two different concentrations (8%, 14%). An excised sample of pork tenderloin was also studied. Measurements were made in the phantoms and the pork muscle at different angles by rotating the phantom with respect to the transducer, where 0° and 180° were defined along the fibers, and 90° and 270° across the fibers. Shear waves were generated and measured by a Verasonics ultrasound system equipped with a linear array transducer. For the fibrous phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 3.60  ±  0.03 and 3.18  ±  0.12 m s(-1) and with 14% gelatin were 4.10  ±  0.11 and 3.90  ±  0.02 m s(-1). For the fishing line material phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 2.86  ±  0.20 and 2.44  ±  0.24 m s(-1) and with 14% gelatin were 3.40  ±  0.09 and 2.84  ±  0.14 m s(-1). For the pork muscle, the mean and standard deviations of the shear wave speeds along the fibers (0°) at two different locations were 3.83  ±  0.16 and 3.86  ±  0.12 m s(-1) and across the fibers (90°) were 2.73  ±  0.18 and 2.70  ±  0.16 m s(-1), respectively. The fibrous and fishing line gelatin-based phantoms exhibited anisotropy that resembles that observed in the pork muscle.

Acoustically active injection catheter guided by ultrasound: navigation tests in acutely ischemic porcine hearts.

Catheters are increasingly used therapeutically and investigatively. With complex usage comes a need for more accurate intracardiac localization than traditional guidance can provide. An injection catheter navigated by ultrasound was designed and then tested in an open-chest model of acute ischemia in eight pigs. The catheter is made "acoustically active" by a piezo-electric crystal near its tip, electronically controlled, vibrating in the audio frequency range and uniquely identifiable using pulsed-wave Doppler. Another "target" crystal was sutured to the epicardium within the ischemic region. Sonomicrometry was used to measure distances between the two crystals and then compared with measurements from 2-D echocardiographic images. Complete data were obtained from seven pigs, and the correlation between sonomicrometry and ultrasound measurements was excellent (p < 0.0001, ρ = 0.9820), as was the intraclass correlation coefficient (0.96) between two observers. These initial experimental results suggest high accuracy of ultrasound navigation of the acoustically active catheter prototype located inside the beating left ventricle.

Ultrasound bladder vibrometry method for measuring viscoelasticity of the bladder wall.

Increase in bladder stiffness could be associated with various pathophysiologic conditions. Measuring bladder viscoelasticity could be an important step towards understanding various disease processes and improving patient care. Here, we introduce ultrasound bladder vibrometry (UBV), a novel method for rapid and noninvasive measurement of bladder wall viscoelasticity. UBV uses acoustic radiation force to excite mechanical waves in the bladder wall and track the motion using ultrasound pulse-echo techniques. Fourier domain analysis of the tissue motion versus time is used to calculate the phase velocity dispersion (change of phase velocity as a function of frequency). The measured phase velocity dispersion is fit with the antisymmetric Lamb wave model to estimate tissue elasticity and viscosity. We used finite element analysis of viscoelastic plate deformation to investigate the effect of curvature on Lamb wave dispersion and showed that the effects of curvature are negligible. The feasibility of the UBV technique was demonstrated in ex vivo and in vivo settings. Elasticity and viscosity of excised pig at various filling volumes (V) and pressures (p) were found to be µ1 = 9.6 kPa and µ2 = 0.2 Pa s (V = 187 ml and p = 8.6 mmHg), µ1 = 48.7 kPa and µ2 = 3.5 Pa s (V = 267 ml and p = 17.6 mmHg), and µ1 = 106.9 kPa and µ2 = 1.5 Pa s (V = 327 ml and p = 27.6 mmHg) respectively. Transabdominal measurements in an anesthetized pig found values of bladder elasticity µ1 = 26.1 kPa and viscosity µ2 = 0.9 Pa s and demonstrate the ability of UBV to perform in vivo measurements. The results presented in this paper introduce a novel technique for measuring mechanical properties of the bladder and lay the foundation for further investigation of the effects of pathology on bladder viscoelasticity.

Measurement of viscoelastic properties of in vivo swine myocardium using lamb wave dispersion ultrasound vibrometry (LDUV).

Viscoelastic properties of the myocardium are important for normal cardiac function and may be altered by disease. Thus, quantification of these properties may aid with evaluation of the health of the heart. Lamb wave dispersion ultrasound vibrometry (LDUV) is a shear wave-based method that uses wave velocity dispersion to measure the underlying viscoelastic material properties of soft tissue with plate-like geometries. We tested this method in eight pigs in an open-chest preparation. A mechanical actuator was used to create harmonic, propagating mechanical waves in the myocardial wall. The motion was tracked using a high frame rate acquisition sequence, typically 2500 Hz. The velocities of wave propagation were measured over the 50-400 Hz frequency range in 50 Hz increments. Data were acquired over several cardiac cycles. Dispersion curves were fit with a viscoelastic, anti-symmetric Lamb wave model to obtain estimates of the shear elasticity, µ(1), and viscosity, µ(2) as defined by the Kelvin-Voigt rheological model. The sensitivity of the Lamb wave model was also studied using simulated data. We demonstrated that wave velocity measurements and Lamb wave theory allow one to estimate the variation of viscoelastic moduli of the myocardial walls in vivo throughout the course of the cardiac cycle.

On Lamb and Rayleigh wave convergence in viscoelastic tissues.

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 a shear wave 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 to quantify the 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 the 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 40­500 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.

Generalized response of a sphere embedded in a viscoelastic medium excited by an ultrasonic radiation force.

The response of an embedded sphere in a viscoelastic medium excited by acoustic radiation force has been studied in both the time- and frequency-domains. This model is important because it can be used to characterize the viscoelastic properties of the medium by fitting the response to the theoretical model. The Kelvin-Voigt model has been used exclusively in these models. An extension to the previously reported models is described so that any viscoelastic rheological model can be used. This theoretical development describes the generalized embedded sphere response both in the time and frequency domains. Comparing the results from derivations in both domains showed very good agreement with a median absolute error (MAE) ranging from 0.0044 to 0.0072. Good agreement is demonstrated with finite element model simulations and the theory with a MAE of 0.006. Lastly, results for characterization of gelatin and rubber materials with the new theory are shown where the MAE values were used to determine which rheological model best describes the measured responses.

Lamb wave dispersion ultrasound vibrometry (LDUV) method for quantifying mechanical properties of viscoelastic solids.

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 shear wave 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 the mechanical properties of soft tissues with a plate-like geometry.

Phase velocities and attenuations of shear, Lamb, and Rayleigh waves in plate-like tissues submerged in a fluid (L).

In the past several decades, the fields of ultrasound and magnetic resonance elastography have shown promising results in noninvasive estimates of mechanical properties of soft tissues. These techniques often rely on measuring shear wave velocity due to an external or internal source of force and relating the velocity to viscoelasticity of the tissue. The mathematical relationship between the measured velocity and material properties of the myocardial wall, arteries, and other organs with non-negligible boundary conditions is often complicated and computationally expensive. A simple relationship between the Lamb-Rayleigh dispersion and the shear wave dispersion is derived for both the velocity and attenuation. The relationship shows that the shear wave velocity is around 20% higher than the Lamb-Rayleigh velocity and that the shear wave attenuation is about 20% lower than the Lamb-Rayleigh attenuation. Results of numerical simulations in the frequency range 0-500 Hz are presented.