Matthew W. Urban

Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity

Characterization of tissue elasticity (stiffness) and viscosity has important medical applications because these properties are closely related to pathological changes. Quantitative measurement is more suitable than qualitative measurement (i.e., mapping with a relative scale) of tissue viscoelasticity for diagnosis of diffuse diseases where abnormality is not confined to a local region and there is no normal background tissue to provide contrast. Shearwave dispersion ultrasound vibrometry (SDUV) uses shear wave propagation speed measured in tissue at multiple frequencies (typically in the range of hundreds of Hertz) to solve quantitatively for both tissue elasticity and viscosity. A shear wave is stimulated within the tissue by an ultrasound push beam and monitored by a separate ultrasound detect beam. The phase difference of the shear wave between 2 locations along its propagation path is used to calculate shear wave speed within the tissue. In vitro SDUV measurements along and across bovine striated muscle fibers show results of tissue elasticity and viscosity close to literature values. An intermittent pulse sequence is developed to allow one array transducer for both push and detect function. Feasibility of this pulse sequence is demonstrated by in vivo SDUV measurements in swine liver using a dual transducer prototype simulating the operation of a single array transducer.

AN OVERVIEW OF ELASTOGRAPHY – AN EMERGING BRANCH OF MEDICAL IMAGING

From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.

Comb-Push Ultrasound Shear Elastography (CUSE): A Novel Method for Two-Dimensional Shear Elasticity Imaging of Soft Tissues

Fast and accurate tissue elasticity imaging is essential in studying dynamic tissue mechanical properties. Various ultrasound shear elasticity imaging techniques have been developed in the last two decades. However, to reconstruct a full field-of-view 2-D shear elasticity map, multiple data acquisitions are typically required. In this paper, a novel shear elasticity imaging technique, comb-push ultrasound shear elastography (CUSE), is introduced in which only one rapid data acquisition (less than 35 ms) is needed to reconstruct a full field-of-view 2-D shear wave speed map (40 × 38 mm). Multiple unfocused ultrasound beams arranged in a comb pattern (comb-push) are used to generate shear waves. A directional filter is then applied upon the shear wave field to extract the left-to-right (LR) and right-to-left (RL) propagating shear waves. Local shear wave speed is recovered using a time-of-flight method based on both LR and RL waves. Finally, a 2-D shear wave speed map is reconstructed by combining the LR and RL speed maps. Smooth and accurate shear wave speed maps are reconstructed using the proposed CUSE method in two calibrated homogeneous phantoms with different moduli. Inclusion phantom experiments demonstrate that CUSE is capable of providing good contrast (contrast-to-noise ratio ≥25 dB) between the inclusion and background without artifacts and is insensitive to inclusion positions. Safety measurements demonstrate that all regulated parameters of the ultrasound output level used in CUSE sequence are well below the FDA limits for diagnostic ultrasound.

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.

Acoustic waves in medical imaging and diagnostics.

Up until about two decades ago acoustic imaging and ultrasound imaging were synonymous. The term ultrasonography, or its abbreviated version sonography, meant an imaging modality based on the use of ultrasonic compressional bulk waves. Beginning in the 1990s, there started to emerge numerous acoustic imaging modalities based on the use of a different mode of acoustic wave: shear waves. Imaging with these waves was shown to provide very useful and very different information about the biological tissue being examined. We discuss the physical basis for the differences between these two basic modes of acoustic waves used in medical imaging and analyze the advantages associated with shear acoustic imaging. A comprehensive analysis of the range of acoustic wavelengths, velocities and frequencies that have been used in different imaging applications is presented. We discuss the potential for future shear wave imaging applications.

BIAS OBSERVED IN TIME-OF-FLIGHT SHEAR WAVE SPEED MEASUREMENTS USING RADIATION FORCE OF A FOCUSED ULTRASOUND BEAM

Measurement of shear wave propagation speed has important clinical applications because it is related to tissue stiffness and health state. Shear waves can be generated in tissues by the radiation force of a focused ultrasound beam (push beam). Shear wave speed can be measured by tracking its propagation laterally from the push beam focus using the time-of-flight principle. This study shows that shear wave speed measurements with such methods can be transducer, depth and lateral tracking range dependent. Three homogeneous phantoms with different stiffness were studied using curvilinear and linear array transducer. Shear wave speed measurements were made at different depths, using different aperture sizes for push and at different lateral distance ranges from the push beam. The curvilinear transducer shows a relatively large measurement bias that is depth dependent. The possible causes of the bias and options for correction are discussed. These bias errors must be taken into account to provide accurate and precise time-of-flight shear wave speed measurements for clinical use.

Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging With a Phased Array Transducer

Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode imaging quality thanks to its effectiveness in suppressing imaging artifacts associated with ultrasound reverberation, phase aberration, and clutter noise. In ultrasound shear wave elastography (SWE), because the shear wave motion signal is extracted from the ultrasound signal, these noise sources can significantly deteriorate the shear wave motion tracking process and consequently result in noisy and biased shear wave motion detection. This situation is exacerbated in in vivo SWE applications such as heart, liver, and kidney. This paper, therefore, investigated the possibility of implementing harmonic imaging, specifically pulse-inversion harmonic imaging, in shear wave tracking, with the hypothesis that harmonic imaging can improve shear wave motion detection based on the same principles that apply to general harmonic B-mode imaging. We first designed an experiment with a gelatin phantom covered by an excised piece of pork belly and show that harmonic imaging can significantly improve shear wave motion detection by producing less underestimated shear wave motion and more consistent shear wave speed measurements than fundamental imaging. Then, a transthoracic heart experiment on a freshly sacrificed pig showed that harmonic imaging could robustly track the shear wave motion and give consistent shear wave speed measurements of the left ventricular myocardium while fundamental imaging could not. Finally, an in vivo transthoracic study of seven healthy volunteers showed that the proposed harmonic imaging tracking sequence could provide consistent estimates of the left ventricular myocardium stiffness in end-diastole with a general success rate of 80% and a success rate of 93.3% when excluding the subject with Body Mass Index higher than 25. These promising results indicate that pulse-inversion harmonic imaging can significantly improve shear wave motion tracking and thus potentially facilitate more robust assessment of tissue elasticity by SWE.

Error in estimates of tissue material properties from shear wave dispersion ultrasound vibrometry

Shear wave velocity measurements are used in elasticity imaging to find the shear elasticity and viscosity of tissue. A technique called shear wave dispersion ultrasound vibrometry (SDUV) has been introduced to use the dispersive nature of shear wave velocity to locally estimate the material properties of tissue. Shear waves are created using a multifrequency ultrasound radiation force, and the propagating shear waves are measured a few millimeters away from the excitation point. The shear wave velocity is measured using a repetitive pulse-echo method and Kalman filtering to find the phase of the harmonic shear wave at 2 different locations. A viscoelastic Voigt model and the shear wave velocity measurements at different frequencies are used to find the shear elasticity (mu1) and viscosity (mu2) of the tissue. The purpose of this paper is to report the accuracy of the SDUV method over a range of different values of mu1 and mu2. A motion detection model of a vibrating scattering medium was used to analyze measurement errors of vibration phase in a scattering medium. To assess the accuracy of the SDUV method, we modeled the effects of phase errors on estimates of shear wave velocity and material properties while varying parameters such as shear stiffness and viscosity, shear wave amplitude, the distance between shear wave measurements (Deltatau), signal-to-noise ratio (SNR) of the ultrasound pulse-echo method, and the frequency range of the measurements. We performed an experiment in a section of porcine muscle to evaluate variation of the aforementioned parameters on the estimated shear wave velocity and material property measurements and to validate the error prediction model. The model showed that errors in the shear wave velocity and material property estimates were minimized by maximizing shear wave amplitude, pulse-echo SNR, Deltatau, and the bandwidth used for shear wave measurements. The experimental model showed optimum performance could be obtained for Deltatau = 3-6 mm, SNR ges35 dB, with a frequency range of 100 to 600 Hz, and with a shear wave amplitude on the order of a few microns down to 0.5 mum. The model provides a basis to explore different parameters related to implementation of the SDUV method. The experiment confirmed conclusions made by the model, and the results can be used for optimization of SDUV.

Shearwave dispersion ultrasound vibrometry (sduv) on swine kidney

Shearwave dispersion ultrasound vibrometry (SDUV) is used to quantify both tissue shear elasticity and shear viscosity by evaluating dispersion of shear wave propagation speed over a certain bandwidth (50 to 500 Hz). The motivation for developing elasticity imaging techniques is the desire to diagnose disease processes. However, it is important to study the mechanical properties of healthy tissues; such data can enhance clinical knowledge and improve understanding of the mechanical properties of tissue. The purpose of this study is to evaluate the feasibility of using SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity in healthy swine kidneys. Eight excised kidneys from female pigs were used in these in vitro experiments and a battery of tests was performed to gain insight into the material proper ties of the renal cortex. In these 8 kidneys, the overall renal cortex elasticity and viscosity were 1.81 ± 0.17 kPa and 1.48 ± 0.49 Pa-s, respectively. In an analysis of the material properties over time after excision, there was not a statistically significant difference in shear elasticity over a 24-h period, but a statistically significant difference in shear viscosity was found. Homogeneity of the renal cortex was examined and it was found that shear elasticity and shear viscosity were statistically different within a kidney, suggesting global tissue inhomogeneity. In creases of more than 30% in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Finally, it was found that the renal cortex is rather anisotropic. Two values for shear elasticity and shear viscosity were measured depending on shear wave propagation direction. These various tests elucidated different aspects of the material properties and the structure of the ex vivo renal cortex.