Chen, Shigao

Vibro-acoustography is a method for imaging the acoustic energy emitted from objects in response to an oscillatory radiation force produced by two interfering focused beams of ultrasound [M. Fatemi and J. F. Greenleaf, Science 280, 82–85 (1998)]. To facilitate quantitative study, a model is presented that describes the behavior of an elastic sphere in two plane ultrasound waves of slightly different frequencies. The vibrating velocity and the resulting acoustic emission of the sphere at the difference frequency are derived from the radiation force and the impedance of the sphere. For small steel spheres in water, the velocity and emission are predicted to have a simple relationship with the difference frequency and the size of the sphere. Experiments on small stainless steel spheres of different size are carried out for a number of difference frequencies, with a laser interferometer to measure the velocity of the sphere and a calibrated hydrophone to measure the acoustic emission from the sphere. The experimental results fit the model description well. This means that vibro-acoustography may be useful in quantitative measurement.

New vibration pulses are proposed to increase the power of shear waves induced by ultrasound radiation force in a tissue region with a preferred spectral distribution. The new pulses are sparsely sampled from an orthogonal frequency wave composed of several sinusoidal signals. Those sinusoidal signals have different frequencies and are orthogonal to each other. The phase and amplitude of each sinusoidal signal are adjusted to control the shape of the orthogonal frequency wave. Amplitude of the sinusoidal signal is increased as its frequency increases to compensate for higher loss at higher frequency in the tissue region. The new vibration pulses and detection pulses can be interleaved for array transducer applications. The experimental results show that the new vibration pulses significantly increases induced tissue vibration with the same peak ultrasound intensity, compared with the binary vibration pulses.

Tissue mechanical properties can be obtained by algebraic direct inversion (ADI) of the shear-wave motion differential equation, which is insensitive to reflection and geometry of the pushing beam. Shear waves normally generated by a focused ultrasound pushing beam have limited spatial extent in depth and are transient in time, leading to noisy and unstable ADI results. A comb-shape acoustic radiation force distribution can generate shear waves with longer spatial extent and time duration, facilitating more robust ADI. For 400 μs, a linear array transducer simultaneously transmitted four unfocused pushing beams (12 on elements for each pushing beam, 8 off elements between beams) into a tissue-mimicking phantom (∼1.5 kPa) with a cylindrical inclusion (∼4 kPa). The ultrasound system (Verasonics Inc.) then immediately switched to flash imaging mode (frame rate = 2 kHz, spatial resolution = 0.31 mm) to measure shear-wave displacements in a 38 mm by 30 mm domain that was used for ADI. The reconstructed 2D shear elasticity map provides accurate shear elasticity estimates (background = 1.5 kPa with 7% variance; inclusion = 3.9 kPa with 15% variance) and excellent contrast between the background and inclusion.

The acoustic radiation force (ARF), which signifies the average transfer of momentum from the sound wave to the propagating medium, is nowadays frequently used to compute the mean displacement field in soft tissues due to the action of a focused ultrasound beam. In situations when the sound field used to generate the ARF is modulated, the latter depends on both spatial and temporal derivatives of the acoustic intensity. Unfortunately, the numerical computation of the nonlinear acoustic solution due to modulated focused ultrasound beam is complicated by the presence of two disparate time scales in the formulation. To deal with the problem, the KZK-type spatial scaling is complemented by its dual-time-scale companion, where the temporal coordinate is split into its “fast” and “slow” components, allowing one to track the ultrasound-scale oscillations and modulation-scale variations separately in the solution. In this case, the nonlinear acoustic solution (and consequently the ARF) can be effectively computed in the “fast” frequency domain and “slow” time domain for any given modulation envelope, transient, or steady-state. The proposed developments are both validated by the experimental results and illustrated via numerical examples that show the effectiveness of the computational scheme.

In the field of tissue engineering, monitoring the elasticity of developing tissue cultures is important for evaluating their growth and maturation. In this work, we used wave propagation methods to measure the elasticity of thin tissue-mimicking layers to test the feasibility of measuring the elasticity of developing tissue cultures. We developed finite element and analytical models for investigating this problem and found good agreement between the results from both models. We used ultrasound radiation force to induce propagating waves, and the waves are measured using high frame rate ultrasound imaging at 10 kHz. The wave modes were identified and compared with an analytic model for Rayleigh wave propagation in a thin elastic layer bound to a solid substrate. The same gelatin mixture was used to make phantoms 1, 4, and 50 mm thick, where the phantom with 50 mm thickness was used as control and evaluated with shear wave imaging methods. The analytic model was used to fit data from experiments in the large block and thin layers of 1 and 4 mm thick, and the measured shear moduli were 22.7, 21.8, and 22.5 kPa, respectively. These results provide a validation for measurement of elasticity in thin elastic layers.

Propagating shear waves in tissue can be measured with high frame rate Doppler or correlation methods. The measured characteristics of the shear waves, such as speed versus frequency, can be used to deduce material properties such as complex viscoelastic modulus using physics models appropriate to the geometry and properties of the tissue. This inverse problem is characterized by calculating the storage and loss modulus as a function of frequency and requires appropriate tissue motion, which in turn requires optimized dynamic radiation force distributions. We will discuss novel radiation force distributions that provide enhanced tissue motions appropriate to dealing with the inverse problem of determining tissue material properties from ultrasonically measured tissue motion.

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.

Characterization of viscoelastic soft tissues and materials has been a subject of active research for the past two decades. Techniques involving measuring the motion of embedded spheres in viscoelastic media have been employed to measure the viscoelastic material properties of the media surrounding the sphere. The published work using this technique has been restricted to using the Kelvin–Voigt model, which has worked for gelatin-based materials. We report an extension of this method using different viscoelastic rheological models such as the Maxwell, generalized Maxwell, Zener, and Kelvin–Voigt fractional derivative models. We performed experiments using a focused 3-MHz transducer to produce radiation force and a 7.5-MHz pulse-echo transducer to measure the sphere motion. Two phantoms were tested; one made of gelatin and another made of rubber with stainless steel spheres embedded in the materials. The response was fitted with the generalized theoretical model to find the material properties over bandwidths of 25–3000 Hz. The median absolute errors ranged from 0.0036–0.0421 and 0.0365–0.0879 for the gelatin and rubber phantoms, respectively. This generalized method offers added flexibility to characterize different types of viscoelastic materials using the most appropriate rheological model. [Work supported in part by NIH Grant nos. EB002167 and DK082408.]

Multiple methods have been proposed to characterize the viscoelastic material properties of soft tissues to differentiate normal from pathological tissue. Shearwave dispersion ultrasound vibrometry is a method that uses the dispersion of the shear wave velocity to characterize tissue shear elasticity and viscosity. It has recently been shown [M. W. Urban and J. F. Greenleaf, Phys. Med. Biol. 54, 5919–5933 (2009)] that the Kramers–Kronig relationships can be applied to shear wave measurements in ex vivo skeletal muscle over a frequency bandwidth of 100–600 Hz. We will describe this process where shear wave attenuation is modeled using a power law, and the shear wave velocity dispersion is predicted by applying the Kramers–Kronig relationships. In this study, we apply this method to shear wave propagation measurements made in different soft tissues such as ex vivo porcine skeletal muscle and kidney and in vivo porcine liver. The shear wave velocity predictions using the Kramers–Kronig relationships agree with the velocity measurements. The mean square error for these tissues ranged from 0.0024–0.0625 m2/s2. The Kramers–Kronig relationships can be used in shear wave propagation measurements in different types of soft tissues. [This work was supported in part by NIH Grants Nos. EB002167 and DK082408.]