Zhao, Heng

Abstract 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.

Calf muscles and Achilles tendon play important roles in functional activities. However, it is not clear how biomechanical properties of the uniarticular soleus (SOL) and biarticular gastrocnemius muscle and Achilles tendon, including the fascicle length, pennation angle, and stiffness, change concurrently post stroke. Biomechanical properties of the medial gastrocnemius (GM) and soleus muscles were evaluated bilaterally in 10 hemiparetic stroke survivors using combined ultrasonography-biomechanical measurements. Biomechanical properties of the Achilles tendon including the length, cross-sectional area (CSA), stiffness, and Young's modulus were evaluated, together with calf muscle biomechanical properties. Gastrocnemius and SOL contributions were separated using flexed and extended knee positions. The impaired side showed decreased fascicle length (GM: 6%, P = 0.002 and SOL: 9%, P = 0.03, at full knee extension and 0° ankle dorsiflexion) and increased fascicular stiffness (GM: 64%, P = 0.005 and SOL: 19%, P = 0.012, at a common 50 N force level). In contrast, Achilles tendon on the impaired side showed changes in the opposite direction as the muscle fascicles with increased tendon length (5%, P < 0.001), decreased tendon CSA (5%, P = 0.04), decreased tendon stiffness (42%, P < 0.001) and Young's modulus (30%, P < 0.001) compared with the unimpaired side. The fascicle and tendon stiffness changes were correlated negatively to the corresponding fascicle and tendon length changes, and decrease in Achilles tendon stiffness was correlated to the increases of SOL and GM fascicular stiffness ( P < 0.05). Characterizations of calf muscle fascicles and Achilles tendon biomechanical properties help us better understand concurrent changes of fascicles and tendon as part of the calf muscle-tendon unit and facilitate development of more effective treatments.

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.

Robust shear-wave motion detection is essential for producing reliable shear elasticity measurements for ultrasound shear-wave elastography (SWE). However, because shear-wave motion is extracted from radiofrequency signals which can be heavily contaminated by noise, shear-wave motion detection can be very challenging, especially for in vivo applications. This study investigated the implementation of harmonic imaging (HI) to facilitate more robust shear-wave tracking based on HI’s effectiveness in suppressing imaging noise associated with ultrasound reverberation, phase aberration, and clutter noise. A HI shear-wave tracking sequence was developed combining the pulse-inversion HI method with the plane wave imaging technique to transmit phase-inverted pulses at a high frame rate of several kilohertz. The backscattered ultrasound signals from phase-inverted pulses were added to suppress the fundamental and enhance the second harmonic component, from which the shear-wave motion was extracted. A pork belly phantom experiment showed that HI could significantly improve shear-wave motion detection by producing almost three-fold less underestimation of shear-wave motion and over ten-fold more precision for shear-wave speed measurements than fundamental imaging. An in vivo transthoracic case study of a human heart showed that HI substantially improved the success rate of shear-wave motion detection and could provide consistent estimates of the left ventricle myocardium stiffness.

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.