Citations

Wormlike micellar fluids are viscoelastic and their mechanical properties have been evaluated with mechanically generated shear waves combined with optical detection as well as rheological testing. In this work, we describe the use of acoustic radiation force and ultrafast ultrasound imaging to generate shear waves and measure their propagation, respectively. This shear wave elastography (SWE) method has been used to measure the viscoelastic mechanical properties in tissue-mimicking phantoms and soft tissues. We tested micellar fluids made from cetrimonium bromide (CTAB) and sodium salicylate (NaSAL) with a 5:3 ratio with different concentrations (100, 200, 300, and 400 mM). We fit an extended Maxwell model to the rheological test data (0.001-15.91Hz) and used the model parameters to calculate the shear wave phase velocity in the range of the SWE data (100-500 Hz). The phase velocities calculated from the rheology testing compared well with the SWE results. The mean absolute error was less than 0.02 m/s for all the micellar fluids tested. The SWE method is nondestructive and can be used for characterization of the viscoelasticity of micellar fluids, which could be used as a model for biological tissues. [This work was supported in part by grant R01DK092255.]

Shear wave elastography (SWE) is clinically used for the measurement of soft tissue mechanical properties. Most SWE methods assume that the tissue is elastic, but soft tissues are inherently viscoelastic. The viscoelasticity can be characterized by examining phase velocity dispersion. Methods to extract the phase velocities from the spatiotemporal data, v(x,t), involve using a two-dimensional Fourier transform. The Fourier representation, V(k,f), is searched for peaks that correspond to the phase velocities. We present a method that uses the Multiple Signal Classification (MUSIC) method to provide robust estimation of the phase velocity dispersion curves. We compared results from the MUSIC method with the current approach of searching for peaks in the V(k,f) representation. We tested this method on digital phantom data created using finite element models (FEMs) in viscoelastic media excited by a simulated acoustic radiation force push from a curved linear array. We evaluated the algorithm with different levels of added noise. Additionally, we tested the methods on data acquired in viscoelastic phantoms with a Verasonics system. The MUSIC algorithm provided dispersion estimation with lower errors than the conventional peak search strategy. This method can be used for evaluation of wave velocity dispersion in viscoelastic tissues and guided wave propagation. [This work was supported in part by grant R01DK092255.]

Kidney transplantation is one treatment for end-stage renal disease. Transplant rejection is typically evaluated with an invasive biopsy. Noninvasive methods for evaluating renal transplants would be beneficial for frequent evaluation. We propose the use of shear wave elastography (SWE) to evaluate viscoelastic properties in renal transplants. Further, we also use acoustoelasticity to measure the nonlinear modulus of the renal transplants. Acoustoelasticity is the phenomenon where the shear wave velocity (SWV) in a material varies with applied stress and is quantified by a nonlinear modulus, A. By applying pressure with the ultrasound transducer, stress is applied to the kidney under investigation and B-mode imaging was used to measure induced strain and SWE was used to make measurements of SWV. Using relationships involving the measured strain and shear moduli at different compression levels, we can obtain estimates of A. In our ongoing study, we use a General Electric Logiq E9 to perform SWE measurements in renal transplant patients coming for protocol biopsies. We have studied 63 patients with SWE to quantify viscoelastic properties of the transplanted kidney. We have obtained data from 19 patients for estimation of the nonlinear modulus, A. We compared the measured viscoelastic and nonlinear shear parameters with clinical variables such as the serum creatinine, Banff biopsy scores, and resistive index. We continue to evaluate these methods and their efficacy as indicators for transplant rejection.

Viscoelastic micellar fluid characteristics have been measured with mechanically generated shear waves and showed good agreement to shear oscillatory methods. In this paper, shear waves in wormlike micellar fluids using ultrasound were successfully generated and detected. Micellar fluids of different concentrations (100, 200, 300, and 400 mM) were studied with ultrasound-based and conventional rheology methods. The measured micellar fluid complex modulus from oscillatory shear tests between 0.001 and 15.91 Hz was characterized with an extended Maxwell fluid model. The elastic and viscous parameters found using rheological testing were used to estimate shear wave phase velocity over a frequency range from 100 to 500 Hz, and compared to shear wave velocity measured with ultrasound-based methods with a mean absolute error 0.02 m/s. The shear wave frequency content was studied and an increase in shear wave center frequency was found as a function of micellar fluid concentration. Moreover, the bias found in the shear wave group velocity with respect to rheological measurement is attributed to the micellar fluid viscous component. Finally, the shear wave phase velocity evaluated at the center frequency agreed well with the rheological measurements.

Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low–energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low–energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low–energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β 1-integrin) ex vivo . A 3-week low–energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low–energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low–energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.

In conventional shear wave elastography materials are assumed to be linear, elastic, homogeneous, and isotropic. These assumptions are important to account for in certain tissues because they are not always appropriate. Many tissues such as skeletal muscle, the kidney, and the myocardium are anisotropic. Shear waves can be used to investigate the directionally dependent mechanical properties of anisotropic media. To study these tissues in a systematic way and to account for the effects of the anisotropic architecture, laboratory-based phantoms are desirable. We will report on several phantom-based approaches for studying shear wave anisotropy, assuming that these materials are transversely isotropic. Phantoms with embedded fibers were used to mimic anisotropic tissues. Homogeneous phantoms were compressed to induce transverse isotropy according to the acoustoelastic phenomenon, which is related to nonlinear behavior of the materials. The fractional anisotropy of these phantoms was quantified to compare with measurements made in soft tissues. In addition, soft tissues are also viscoelastic, and we have developed a method to model viscoelastic transversely isotropic materials with the finite element method (FEM). The viscoelastic property estimation from phantom experiments and FEM simulations will also be discussed.

Elasticity imaging has emerged as a viable clinical tool for assisting in diagnosis of certain diseases such as liver fibrosis and cancer. Many methods have been developed for generating and measuring shear waves in soft tissues. The advantage of using shear waves is that the shear wave velocity is proportional to the mechanical material properties of the tissues under investigation. Soft tissues are inherently viscoelastic and considerable effort has been made to quantify the dispersion, or variation of frequency, of the velocity and attenuation of shear waves. This is accomplished by measuring the shear wave motion and using Fourier-based techniques to extract the shear wave velocity and attenuation. Additional considerations are made in tissues where geometric dispersion is also present such as in the heart. Viscoelastic characterization of the shear viscoelasticity of soft tissues in vivo such as human liver, human kidney, and swine heart will be shown. We will also demonstrate parameterization of the results by using a model-free approach or by fitting the shear wave velocity dispersion to rheological models. The diagnostic value of the viscoelastic parameters will be discussed for each particular application. [This work was supported in part by NIH Grant Nos. DK092255, DK082408, and EB002167.]

Measurements of viscoelasticity with shear wave velocity dispersion requires measurements over a large bandwidth. In this study, we explored the parameters that modulate the frequency characteristics of shear waves induced using radiation force push beams. We used a Verasonics ultrasound scanner equipped with a linear array transducer. We performed measurements of shear wave motion induced using both focused and unfocused ultrasound beams. Measurements were made in elastic phantoms with shear moduli of 1, 4, and 16 kPa. The number of elements used for the unfocused beams were varied from 8 to 24, and for the focused beams from 16 to 128. The shear wave motion was tracked using plane wave imaging, and a one-dimensional autocorrelation algorithm applied to the acquired in-phase/quadrature data. At each pixel we calculated the fast Fourier transform of the data and found the center frequency, center-of-gravity, and −3 dB bandwidth. We compared the frequency characteristics from the different push beams. The frequency characteristics were found to be spatially variant and dependent on the number of elements used as well as the shear modulus of the medium. The center frequency, center-of-gravity, and the bandwidth were found to be correlated to one another, and strongly associated with the stiffness of the medium.