Ivan Z. Nenadic

Material property estimation for tubes and arteries using ultrasound radiation force and analysis of propagating modes

Arterial elasticity has been proposed as an independent predictor of cardiovascular diseases and mortality. Identification of the different propagating modes in thin shells can be used to characterize the elastic properties. Ultrasound radiation force was used to generate local mechanical waves in the wall of a urethane tube or an excised pig carotid artery. The waves were tracked using pulse-echo ultrasound. A modal analysis using two-dimensional discrete fast Fourier transform was performed on the time-space signal. This allowed the visualization of different modes of propagation and characterization of dispersion curves for both structures. The urethane tube/artery was mounted in a metallic frame, embedded in tissue-mimicking gelatin, cannulated, and pressurized over a range of 10-100 mmHg. The k-space and the dispersion curves of the urethane tube showed one mode of propagation, with no effect of transmural pressure. Fitting of a Lamb wave model estimated Youngs modulus in the urethane tube around 560 kPa. Youngs modulus of the artery ranged from 72 to 134 kPa at 10 and 100 mmHg, respectively. The changes observed in the artery dispersion curves suggest that this methodology of exciting mechanical waves and characterizing the modes of propagation has potential for studying arterial elasticity.

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.

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 organs 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.

Shearwave dispersion ultrasound vibrometry applied to in vivo myocardium

Diastolic properties of the myocardium are important for normal cardiac function and may contribute to the condition of heart failure. Measuring the viscoelastic properties of the left ventricular myocardium is difficult in vivo using noninvasive methods. In this study, we used a mechanical actuator to create harmonic, propagating mechanical waves in the myocardial tissue in vivo. The motion was measured using ultrasound imaging techniques. The wave propagation velocities were measured over the 50–350Hz frequency range. The dispersion curves were fit with an asymmetrical Lamb wave model to obtain estimates of the shear elasticity and viscosity of the myocardial tissue. The method was applied to estimate viscoelastic properties of the myocardium during diastole and systole.

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, μ1, and viscosity, μ2 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.

Model-free quantification of shear wave velocity and attenuation in tissues and its in vivo application

We validate a technique for model-free measurement of shear wave velocity and attenuation. A mechanical shaker was used to excite harmonic plane and cylindrical waves in phantoms and excised tissue. Radiation force was used to excite impulsive cylindrical waves. 2D FFT of the displacement yielded the k-space whose coordinates are frequency and the wave number. The shear wave velocity at each frequency was obtained by finding the maximum at the given frequency in k-space and dividing the frequency coordinate by the wave number coordinate. The attenuation (α) at a given frequency was calculated using α = FWHM × π/√3, where FWHM is the full width at half maximum of the k-space peak along the given frequency. This method was applied to measure shear wave velocity and attenuation of transplanted kidneys and livers, and in the thyroid tumor, and compare it to the healthy tissues. The velocities and attenuations at each frequency for various excitation methods agree within one standard deviation. The k-space est...

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.

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.

Noninvasive Evaluation of Bladder Wall Mechanical Properties as a Function of Filling Volume: Potential Application in Bladder Compliance Assessment.

Purpose We propose a novel method to monitor bladder wall mechanical properties as a function of filling volume, with the potential application to bladder compliance assessment. The proposed ultrasound bladder vibrometry (UBV) method uses ultrasound to excite and track Lamb waves on the bladder wall from which its mechanical properties are derived by fitting measurements to an analytical model. Of particular interest is the shear modulus of bladder wall at different volumes, which we hypothesize, is similar to measuring the compliance characteristics of the bladder. Materials and Methods Three experimental models were used: 1) an ex vivo porcine model where normal and aberrant (stiffened by formalin) bladders underwent evaluation by UBV; 2) an in vivo study to evaluate the performance of UBV on patients with clinically documented compliant and noncompliant bladders undergoing UDS; and 3) a noninvasive UBV protocol to assess bladder compliance using oral hydration and fractionated voiding on three healthy volunteers. Results The ex vivo studies showed a high correlation between the UBV parameters and direct pressure measurement (R2 = 0.84–0.99). A similar correlation was observed for 2 patients with compliant and noncompliant bladders (R2 = 0.89–0.99) undergoing UDS detrusor pressure-volume measurements. The results of UBV on healthy volunteers, performed without catheterization, were comparable to a compliant bladder patient. Conclusion The utility of UBV as a method to monitor changes in bladder wall mechanical properties is validated by the high correlation with pressure measurements in ex vivo and in vivo patient studies. High correlation UBV and UDS in vivo studies demonstrated the potential of UBV as a bladder compliance assessment tool. Results of studies on healthy volunteers with normal bladders demonstrated that UBV could be performed noninvasively. Further studies on a larger cohort are needed to fully validate the use of UBV as a clinical tool for bladder compliance assessment.

Ex Vivo measurements of myocardial viscoelasticity using Shearwave Dispersion Ultrasound Vibrometry (SDUV)

Stiffening of the left ventricle can compromise the ability of the heart to pump sufficient amounts of blood into the systemic circulation and could lead to heart failure. Quantifying mechanical properties of the left ventricular (LV) myocardium using a noninvasive technique would be of great benefit in clinical settings. We investigated the feasibility of using Shearwave Dispersion Ultrasound Vibrometry (SDUV) to measure viscoelasticity of the myocardium. A mechanical actuator was used to induce shear waves at multiple frequencies (40–500 Hz) in excised LV myocardium and urethane rubber samples, and a pulse echo ultrasound transducer was used to detect the motion at each frequency. An anti-symmetric Lamb wave model was fit to the shear wave dispersion curves in four orthogonal directions to obtain elastic and viscous moduli.