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1.  Multi-source and Multi-directional Shear Wave Generation with Intersecting Steered Ultrasound Push Beams 
Elasticity imaging is becoming established as a means of assisting in diagnosis of certain diseases. Shear wave-based methods have been developed to perform elasticity measurements in soft tissue. Comb-push ultrasound shear elastography (CUSE) is one of these methods which apply acoustic radiation force to induce the shear wave in soft tissues. CUSE uses multiple ultrasound beams that are transmitted simultaneously to induce multiple shear wave sources into the tissue, with improved shear wave signal-to-noise-ratio (SNR) and increased shear wave imaging frame rate.
We propose a novel method that uses steered push beams (SPB) that can be applied for beam formation for shear wave generation. In CUSE beamforming, either unfocused or focused beams are used to create the propagating shear waves. In SPB methods we use unfocused beams that are steered at specific angles. The interaction of these steered beams causes shear waves to be generated in more of a random nature than in CUSE. The beams are typically steered over a range of 3–7° and can either be steered to the left (−θ) or right (+θ). We performed simulations of 100 configurations using Field II and found the best configurations based on spatial distribution of peaks in the resulting intensity field. The best candidates were ones with a higher number of the intensity peaks distributed over all depths in the simulated beamformed results. Then these optimal configurations were applied on a homogeneous phantom and two different phantoms with inclusions. In one of the inhomogeneous phantoms we studied two spherical inclusions with 10 and 20 mm diameters, and in the other phantom we studied cylindrical inclusions with diameters ranging from 2.53–16.67 mm. We compared these results to those obtained using conventional CUSE with unfocused and focused beams. The mean and standard deviation of the resulting shear wave speeds were used to evaluate the accuracy of the reconstructions by examining bias with nominal values for the phantoms as well as the contrast-to-noise ratio in the inclusion phantom results. In general the CNR was higher and the bias was lower using the SPB method compared to the CUSE realizations except in the largest inclusions. In the cylindrical inclusion with 10.4 mm diameter, the range of CNR in CUSE methods ranged between 18.52 and 22.02 and the bias ranged between 5.50 and 11.12% while for SPB methods provided CNR values between 23.07 and 48.90 and bias values between 3.78 and 9.22%. In a smaller cylindrical inclusion with diameter of 4.05 mm, CUSE methods gave CNR between 14.69 and 22.28 and bias ranging between 28.95 and 29.28% while the SPB methods provided CNR values between 16.7 and 25.2 and bias values varying from 25.54 to 30.44%. The SPB method provides a flexible framework to produce shear wave sources that are widely distributed within the field-of-view for robust shear wave speed imaging.
doi:10.1109/TUFFC.2014.006805
PMCID: PMC4400871  PMID: 25881343
2.  Modeling Transversely Isotropic, Viscoelastic, Incompressible Tissue-like Materials with Application in Ultrasound Shear Wave Elastography 
Physics in medicine and biology  2015;60(3):1289-1306.
In this paper, we propose a method to model the shear wave propagation in transversely isotropic, viscoelastic and incompressible media. The targeted application is ultrasound-based shear wave elastography for viscoelasticity measurements in anisotropic tissues such as the kidney and skeletal muscles. The proposed model predicts that if the viscoelastic parameters both across and along fiber directions can be characterized as a Voigt material, then the spatial phase velocity at any angle is also governed by a Voigt material model. Further, with the aid of Taylor expansions, it is shown that the spatial group velocity at any angle is close to a Voigt type for weakly attenuative materials within a certain bandwidth. The model is implemented in a finite element code by a time domain explicit integration scheme and shear wave simulations are conducted. The results of the simulations are analyzed to extract the shear wave elasticity and viscosity for both the spatial phase and group velocities. The estimated values match well with theoretical predictions. The proposed theory is further verified by an ex vivo tissue experiment measured in a porcine skeletal muscle by an ultrasound shear wave elastography method. The applicability of the Taylor expansion to analyze the spatial velocities is also discussed. We demonstrate that the approximations from the Taylor expansions are subject to errors when the viscosities across or along the fiber directions are large or the maximum frequency considered is beyond the bandwidth defined by radii of convergence of the Taylor expansions.
doi:10.1088/0031-9155/60/3/1289
PMCID: PMC4314720  PMID: 25591921
transversely isotropic; viscoelastic; incompressible; finite element; shear wave; ultrasound elastography
3.  Two-dimensional Shear Wave Elastography on Conventional Ultrasound Scanners with Time Aligned Sequential Tracking (TAST) and Comb-push Ultrasound Shear Elastography (CUSE) 
Two-dimensional (2D) shear wave elastography presents 2D quantitative shear elasticity maps of tissue, which are clinically useful for both focal lesion detection and diffuse disease diagnosis. Realization of 2D shear wave elastography on conventional ultrasound scanners, however, is challenging due to the low tracking pulse-repetition-frequency (PRF) of these systems. While some clinical and research platforms support software beamforming and plane wave imaging with high PRF, the majority of current clinical ultrasound systems do not have the software beamforming capability, which presents a critical challenge for translating the 2D shear wave elastography technique from laboratory to clinical scanners. To address this challenge, this paper presents a Time Aligned Sequential Tracking (TAST) method for shear wave tracking on conventional ultrasound scanners. TAST takes advantage of the parallel beamforming capability of conventional systems and realizes high PRF shear wave tracking by sequentially firing tracking vectors and aligning shear wave data in the temporal direction. The Comb-push Ultrasound Shear Elastography (CUSE) technique was used to simultaneously produce multiple shear wave sources within the field-of-view (FOV) to enhance shear wave signal-to-noise-ratio (SNR) and facilitate robust reconstructions of 2D elasticity maps. TAST and CUSE were realized on a conventional ultrasound scanner (the General Electric LOGIQ E9). A phantom study showed that the shear wave speed measurements from the LOGIQ E9 were in good agreement to the values measured from other 2D shear wave imaging technologies. An inclusion phantom study showed that the LOGIQ E9 had comparable performance to the Aixplorer (Supersonic Imagine) in terms of bias and precision in measuring different sized inclusions. Finally, in vivo case analysis of a breast with a malignant mass, and a liver from a healthy subject demonstrated the feasibility of using the LOGIQ E9 for in vivo 2D shear wave elastography. These promising results indicate that the proposed technique can enable the implementation of 2D shear wave elastography on conventional ultrasound scanners and potentially facilitate wider clinical applications with shear wave elastography.
doi:10.1109/TUFFC.2014.006628
PMCID: PMC4315508  PMID: 25643079
Shear wave elastography; acoustic radiation force; CUSE; LOGIQ E9
4.  Shear wave vibrometry evaluation in transverse isotropic tissue mimicking phantoms and skeletal muscle 
Physics in medicine and biology  2014;59(24):7735-7752.
Ultrasound radiation force-based methods can quantitatively evaluate tissue viscoelastic material properties. One of the limitations of the current methods is neglecting the inherent anisotropy nature of certain tissues. To explore the phenomenon of anisotropy in a laboratory setting, we created two phantom designs incorporating fibrous and fishing line material with preferential orientations. Four phantoms were made in a cube-shaped mold; both designs were arranged in multiple layers and embedded in porcine gelatin using two different concentrations (8%, 14%). An excised sample of pork tenderloin was also studied. Measurements were made in the phantoms and the pork muscle at different angles by rotating the phantom with respect to the transducer, where 0° and 180° were defined along the fibers, and 90° and 270° across the fibers. Shear waves were generated and measured by a Verasonics ultrasound system equipped with a linear array transducer. For the fibrous phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 3.60 ± 0.03 and 3.18 ± 0.12 m/s and with 14% gelatin were 4.10 ± 0.11 and 3.90 ± 0.02 m/s. For the fishing line material phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 2.86 ± 0.20 and 2.44 ± 0.24 m/s and with 14% gelatin were 3.40 ± 0.09 and 2.84 ± 0.14 m/s. For the pork muscle, the mean and standard deviations of the shear wave speeds along the fibers (0°) at two different locations were 3.83 ± 0.16 and 3.86 ± 0.12 m/s and across the fibers (90°) were 2.73 ± 0.18 and 2.70 ± 0.16 m/s, respectively. The fibrous and fishing line gelatin-based phantoms exhibited anisotropy that resembles that observed in the pork muscle.
doi:10.1088/0031-9155/59/24/7735
PMCID: PMC4442078  PMID: 25419697
Transverse isotropy; Ultrasound; Acoustic radiation force; Phantoms; muscle; Shear wave imaging
5.  External Vibration Multi-directional Ultrasound Shearwave Elastography (EVMUSE): Application in Liver Fibrosis Staging 
IEEE transactions on medical imaging  2014;33(11):2140-2148.
Shear wave speed can be used to assess tissue elasticity, which is associated with tissue health. Ultrasound shear wave elastography techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force are becoming promising alternatives to biopsy in liver fibrosis staging. However, shear waves generated by such methods are typically very weak. Therefore, the penetration may become problematic, especially for overweight or obese patients. In this study, we developed a new method called External Vibration Multi-directional Ultrasound Shearwave Elastography (EVMUSE), in which external vibration from a loudspeaker was used to generate a multi-directional shear wave field. A directional filter was then applied to separate the complex shear wave field into several shear wave fields propagating in different directions. A two-dimensional (2D) shear wave speed map was reconstructed from each individual shear wave field, and a final 2D shear wave speed map was constructed by compounding these individual wave speed maps. The method was validated using two homogeneous phantoms and one multi-purpose tissue-mimicking phantom. Ten patients undergoing liver Magnetic Resonance Elastography (MRE) were also studied with EVMUSE to compare results between the two methods. Phantom results showed EVMUSE was able to quantify tissue elasticity accurately with good penetration. In vivo EVMUSE results were well correlated with MRE results, indicating the promise of using EVMUSE for liver fibrosis staging.
doi:10.1109/TMI.2014.2332542
PMCID: PMC4216646  PMID: 25020066
Directional filter; external vibration; liver fibrosis; magnetic resonance elastography; shear wave elastography; shear wave speed
6.  Noninvasive Assessment of Liver Fibrosis Using Ultrasound-based Shear Wave Measurement and Comparison to Magnetic Resonance Elastography 
Objective
Magnetic Resonance Elastography (MRE) has excellent performance in detecting liver fibrosis and is becoming an alternative to liver biopsy in clinical practice. Ultrasound techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force also have shown promising results for liver fibrosis staging. The objective of this study was to compare ultrasound-based shear wave measurement with MRE.
Methods
In this study, fifty patients (22 males and 28 females, age 19–81) undergoing liver MRE exams were studied using a Philips iU22 ultrasound scanner modified with shear wave measurement functionality. For each subject, 27 shear wave speed measurements were obtained at various locations in the liver parenchyma away from major vessels. The median shear wave speed from all measurements was used to calculate a representative shear modulus μ for each subject. MRE data processing was done by a single analyst blinded to ultrasound results.
Results
Results showed that ultrasound and MRE measurements were correlated (r = 0.86, P < 0.001). Receiver operating characteristic (ROC) analysis was applied to the ultrasound measurement results with the MRE diagnosis as the “ground truth”. The area under the ROC curve for separating patients with minimum fibrosis (defined as shear modulus μMRE ≤ 2.9 kPa) was 0.89 (95% confidence interval [CI]: 0.77–0.95), and the area under the ROC curve for separating patients with advanced fibrosis (defined as μMRE ≥ 5.0 kPa) was 0.96 (95% CI: 0.87–0.99).
Conclusions
Results indicate that the ultrasound shear wave measurement correlates with MRE and is a promising method for liver fibrosis staging.
doi:10.7863/ultra.33.9.1597
PMCID: PMC4145616  PMID: 25154941
Ultrasound; Shear Wave; Liver fibrosis; MRE
7.  Coded Excitation Plane Wave Imaging for Shear Wave Motion Detection 
Plane wave imaging has greatly advanced the field of shear wave elastography thanks to its ultrafast imaging frame rate and the large field-of-view (FOV). However, plane wave imaging also has decreased penetration due to lack of transmit focusing, which makes it challenging to use plane waves for shear wave detection in deep tissues and in obese patients. This study investigated the feasibility of implementing coded excitation in plane wave imaging for shear wave detection, with the hypothesis that coded ultrasound signals can provide superior detection penetration and shear wave signal-to-noise-ratio (SNR) compared to conventional ultrasound signals. Both phase encoding (Barker code) and frequency encoding (chirp code) methods were studied. A first phantom experiment showed an approximate penetration gain of 2-4 cm for the coded pulses. Two subsequent phantom studies showed that all coded pulses outperformed the conventional short imaging pulse by providing superior sensitivity to small motion and robustness to weak ultrasound signals. Finally, an in vivo liver case study on an obese subject (Body Mass Index = 40) demonstrated the feasibility of using the proposed method for in vivo applications, and showed that all coded pulses could provide higher SNR shear wave signals than the conventional short pulse. These findings indicate that by using coded excitation shear wave detection, one can benefit from the ultrafast imaging frame rate and large FOV provided by plane wave imaging while preserving good penetration and shear wave signal quality, which is essential for obtaining robust shear elasticity measurements of tissue.
doi:10.1109/TUFFC.2015.007062
PMCID: PMC4530976  PMID: 26168181
coded excitation; shear wave; elastography; Barker; chirp; shear wave detection
8.  VISCOELASTIC PROPERTIES OF NORMAL AND INFARCTED MYOCARDIUM MEASURED BY A MULTIFREQUENCY SHEAR WAVE METHOD: COMPARISON WITH PRESSURE-SEGMENT LENGTH METHOD 
Ultrasound in medicine & biology  2014;40(8):1785-1795.
Our aims were (i) to compare in vivo measurements of myocardial elasticity by shear wave dispersion ultrasound vibrometry (SDUV) with those by the conventional pressure-segment length method, and (ii) to quantify changes in myocardial viscoelasticity during systole and diastole after reperfused acute myocardial infarction. The shear elastic modulus (μ1) and viscous coefficient (μ2) of left ventricular myocardium were measured by SDUV in 10 pigs. Young’s elastic modulus was independently measured by the pressure-segment length method. Measurements made with the SDUV and pressure-segment length methods were strongly correlated. At reperfusion, μ1 and μ2 in end-diastole were increased. Less consistent changes were found during systole. In all animals, μ1 increased linearly with left ventricular pressure developed during systole. Preliminary results suggest that m1 is preload dependent. This is the first study to validate in vivo measurements of myocardial elasticity by a shear wave method. In this animal model, the alterations in myocardial viscoelasticity after a myocardial infarction were most consistently detected during diastole.
doi:10.1016/j.ultrasmedbio.2014.03.004
PMCID: PMC4118646  PMID: 24814645
Echocardiography; Elasticity; Elastography; Myocardial stiffness; Myocardial infarction; Shear elasticity; Shear wave; Ultrasound; Viscoelasticity
9.  Fast Shear Compounding Using Robust Two-dimensional Shear Wave Speed Calculation and Multi-directional Filtering 
Ultrasound in medicine & biology  2014;40(6):1343-1355.
A fast shear compounding method was developed in this study using only one shear wave push-detect cycle, such that the shear wave imaging frame rate is preserved and motion artifacts are minimized. The proposed method is composed of the following steps: 1. applying a comb-push to produce multiple differently angled shear waves at different spatial locations simultaneously; 2. decomposing the complex shear wave field into individual shear wave fields with differently oriented shear waves using a multi-directional filter; 3. using a robust two-dimensional (2D) shear wave speed calculation to reconstruct 2D shear elasticity maps from each filter direction; 4. compounding these 2D maps from different directions into a final map. An inclusion phantom study showed that the fast shear compounding method could achieve comparable performance to conventional shear compounding without sacrificing the imaging frame rate. A multi-inclusion phantom experiment showed that the fast shear compounding method could provide a full field-of-view (FOV), 2D, and compounded shear elasticity map with three types of inclusions clearly resolved and stiffness measurements showing excellent agreement to the nominal values.
doi:10.1016/j.ultrasmedbio.2013.12.026
PMCID: PMC4011964  PMID: 24613636
shear compounding; shear wave elastography; 2D shear wave speed; directional filter; comb-push; acoustic radiation force
10.  Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging with a Phased Array Transducer 
IEEE transactions on medical imaging  2013;10.1109/TMI.2013.2280903.
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 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 (BMI) 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.
doi:10.1109/TMI.2013.2280903
PMCID: PMC3947393  PMID: 24021638
Harmonic imaging; shear wave elastography; acoustic radiation force; pulse inversion; in vivo human heart; transthoracic scanning; diastolic left ventricle stiffness
11.  Optimized shear wave generation using hybrid beamforming methods 
Ultrasound in medicine & biology  2013;40(1):10.1016/j.ultrasmedbio.2013.08.016.
Elasticity imaging is a medical imaging modality that measures tissue elasticity to aid in diagnosis of certain diseases. Shear wave-based methods have been developed to perform elasticity measurements in soft tissue. These methods often utilize the radiation force mechanism of focused ultrasound to induce shear waves in soft tissue such as liver, kidney, breast, thyroid, and skeletal muscle. The efficiency of the ultrasound beam for producing broadband extended shear waves in soft tissue is very important for widespread use of this modality. Hybrid beamforming combines two types of focusing, conventional spherical and axicon focusing, to produce a beam for generating a shear wave that has increased depth-of–field (DOF) so that measurements can be made with a shear wave with a consistent wave front. Spherical focusing is used in many applications to achieve high lateral resolution, but has low DOF. Axicon focusing, with a cone- shaped transducer can provide good lateral resolution with large DOF. We present our linear aperture design and beam optimization performed using angular spectrum simulations. A large parametric simulation study was performed which included varying the focal depth for the spherical focusing portion of the aperture, the number of elements devoted to spherical and axicon focusing portions of the aperture, and the opening angle used for axicon focusing. The hybrid beamforming method was experimentally tested in two phantoms and the shear wave speed measurement accuracy as well as the DOF for each hybrid beam was evaluated. We compared our results with shear waves generated using only spherical focusing. The results of this study show that hybrid beamforming is capable of producing a beam with increased DOF over which accurate shear wave speed measurements can be made for different size apertures and at different focal depths.
doi:10.1016/j.ultrasmedbio.2013.08.016
PMCID: PMC3849318  PMID: 24139918
shear wave; hybrid beamforming; axicon; shear wave speed; depth-of-field
12.  Comb-push Ultrasound Shear Elastography (CUSE) for Evaluation of Thyroid Nodules: Preliminary In vivo Results 
In clinical practice, an overwhelming majority of biopsied thyroid nodules are benign. Therefore, there is a need for a complementary and noninvasive imaging tool to provide clinically relevant diagnostic information about thyroid nodules to reduce the rate of unnecessary biopsies. The goal of this study was to evaluate the feasibility of utilizing Comb-push Ultrasound Shear Elastography (CUSE) to measure the mechanical properties (i.e., stiffness) of thyroid nodules and use this information to help classify nodules as benign or malignant. CUSE is a fast and robust 2D shear elastography technique in which multiple laterally distributed acoustic radiation force beams are utilized simultaneously to produce shear waves. Unlike other shear elasticity imaging modalities, CUSE does not suffer from limited field of view (FOV) due to shear wave attenuation and can provide a large FOV at high frame rates. To evaluate the utility of CUSE in thyroid imaging, a preliminary study was performed on a group of 5 healthy volunteers and 10 patients with ultrasound (US)-detected thyroid nodules prior to fine needle aspiration biopsy (FNAB). The measured shear wave speeds in normal thyroid tissue and thyroid nodules were converted to Young's modulus (E), indicating a measure of tissue stiffness. Our results indicate an increase in E for thyroid nodules compared to normal thyroid tissue. This increase was significantly higher in malignant nodules compared to benign. The Young's modulus in normal thyroid tissue, benign and malignant nodules were found to be 23.2±8.29 kPa, 91.2±34.8 kPa, and 173.0±17.1 kPa, respectively. Results of this study suggest the utility of CUSE in differentiating between benign and malignant thyroid nodules.
doi:10.1109/TMI.2014.2346498
PMCID: PMC4280299  PMID: 25122532
Cancer; Elasticity; In vivo; Shear Wave Elastography; Thyroid; Ultrasound
13.  Validation of Shear Wave Elastography in Skeletal Muscle 
Journal of biomechanics  2013;46(14):10.1016/j.jbiomech.2013.07.033.
Skeletal muscle is a very dynamic tissue, thus accurate quantification of skeletal muscle stiffness throughout its functional range is crucial to improve the physical functioning and independence following pathology. Shear wave elastography (SWE) is an ultrasound-based technique that characterizes tissue mechanical properties based on the propagation of remotely induced shear waves. The objective of this study is to validate SWE throughout the functional range of motion of skeletal muscle for three ultrasound transducer orientations. We hypothesized that combining traditional materials testing (MTS) techniques with SWE measurements will show increased stiffness measures with increasing tensile load, and will correlate well with each other for trials in which the transducer is parallel to underlying muscle fibers. To evaluate this hypothesis, we monitored the deformation throughout tensile loading of four porcine brachialis whole-muscle tissue specimens, while simultaneously making SWE measurements of the same specimen. We used regression to examine the correlation between Young's modulus from MTS and shear modulus from SWE for each of the transducer orientations. We applied a generalized linear model to account for repeated testing. Model parameters were estimated via generalized estimating equations. The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463 – 0.2425) for parallel transducer trials. Shear waves did not propagate well for both the 45° and perpendicular transducer orientations. Both parallel SWE and MTS showed increased stiffness with increasing tensile load. This study provides the necessary first step for additional studies that can evaluate the distribution of stiffness throughout muscle.
doi:10.1016/j.jbiomech.2013.07.033
PMCID: PMC3818126  PMID: 23953670
Ultrasonography; passive stiffness; materials testing; elastic moduli; shear wave elastography
14.  Comb-push Ultrasound Shear Elastography (CUSE) with Various Ultrasound Push Beams 
IEEE transactions on medical imaging  2013;32(8):1435-1447.
Comb-push Ultrasound Shear Elastography (CUSE) has recently been shown to be a fast and accurate two-dimensional (2D) elasticity imaging technique that can provide a full field-of- view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE – Focused CUSE (F-CUSE) and Marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g. kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging.
doi:10.1109/TMI.2013.2257831
PMCID: PMC3760382  PMID: 23591479
CUSE; comb-push; ultrasound elastography; shear wave; acoustic radiation force; unfocused ultrasound beam; focused ultrasound beam
15.  Acoustic Waves in Medical Imaging and Diagnostics 
Ultrasound in medicine & biology  2013;39(7):1133-1146.
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. Since the 1990s numerous acoustic imaging modalities started to emerge based on the use of a different mode of acoustic wave: shear waves. It was demonstrated that imaging with these waves can provide very useful and very different information about the biological tissue being examined. We will discuss 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 will be presented. We will discuss the potential for future shear wave imaging applications.
doi:10.1016/j.ultrasmedbio.2013.02.006
PMCID: PMC3682421  PMID: 23643056
compressional wave; shear wave; elasticity; viscoelasticity; acoustic imaging; dispersion; anisotropy
17.  In vivo swine kidney viscoelasticity during acute gradual decrease in renal blood flow: pilot study 
Elasticity imaging methods have been used to study kidney mechanical properties and have demonstrated that the kidney elastic modulus increases with disease state. However, studies in swine suggests that kidney elastic modulus is also affected by hemodynamic variables. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a tool to determine renal elasticity and viscosity in vivo. The purpose of this study is directed toward evaluating the feasibility of SDUV for in vivo measurements of healthy swine kidney during acute gradual decease of renal blood flow. In this study in vivo SDUV measurements were made on a group of 5 normal swine kidneys at baseline renal blood flow (RBF) and 25, 50, 75 and 100% decrease in RBF. The shear elastic modulus at full baseline was 7.04 ± 0.92 kPa and 3.48 ± 0.20 kPa at 100% decrease in RBF. The viscosity did not change between baseline (2.23 ± 0.33 Pa·s) and 100% decrease in RBF (2.03 ± 0.32 Pa·s). The data from this study indicates that other variables such as local blood flow, pressure and volume as well as method accuracy need to be measured to illustrate the relationship between shear elasticity and viscosity associated with acute kidney processes.
PMCID: PMC3922126  PMID: 24533039
Renal cortex; elasticity; viscosity
18.  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.
doi:10.1109/TMI.2012.2222656
PMCID: PMC3562367  PMID: 23060325
19.  Shear Wave Speed Measurement Using an Unfocused Ultrasound Beam 
Ultrasound in medicine & biology  2012;38(9):1646-1655.
Tissue elasticity is related to pathology and therefore has important medical applications. Radiation force from a focused ultrasound beam has been used to produce shear waves in tissues for shear wave speed and tissue elasticity measurements. The feasibility of shear wave speed measurement using radiation force for an unfocused ultrasound beam is demonstrated in this study with a linear and a curved array transducer. Consistent measurement of shear wave speed was achieved over a relatively long axial extent (z = 10-40 mm for the linear array, and z = 15-60 mm for the curved array) in 3 calibrated phantoms with different shear moduli. In vivo measurements on the biceps of a healthy volunteer show consistent increase of shear wave speed for the biceps under 0, 1, 2, and 3 kg loading. Advantages and limitations of unfocused push are discussed.
doi:10.1016/j.ultrasmedbio.2012.05.015
PMCID: PMC3413738  PMID: 22766123
Elasticity; Shear wave; Ultrasound radiation force; Unfocused
20.  Comb-push Ultrasound Shear Elastography (CUSE): A Novel Method for Two-dimensional Shear Elasticity Imaging of Soft Tissues 
IEEE transactions on medical imaging  2012;31(9):1821-1832.
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 2D 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 2D shear wave speed map (40 mm × 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 2D 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.
doi:10.1109/TMI.2012.2205586
PMCID: PMC3475422  PMID: 22736690
comb-push; unfocused ultrasound beam; ultrasound elastography; acoustic radiation force; inclusion
21.  In vivo thyroid vibro-acoustography: a pilot study 
BMC Medical Imaging  2013;13:12.
Background
The purpose of this study was to evaluate the utility of a noninvasive ultrasound-based method, vibro-acoustography (VA), for thyroid imaging and determine the feasibility and challenges of VA in detecting nodules in thyroid.
Methods
Our study included two parts. First, in an in vitro study, experiments were conducted on a number of excised thyroid specimens randomly taken from autopsy. Three types of images were acquired from most of the specimens: X-ray, B-mode ultrasound, and vibro-acoustography. The second and main part of the study includes results from performing VA and B-mode ultrasound imaging on 24 human subjects with thyroid nodules. The results were evaluated and compared qualitatively.
Results
In vitro vibro-acoustography images displayed soft tissue structures, microcalcifications, cysts and nodules with high contrast and no speckle. In this group, all of US proven nodules and all of X-ray proven calcifications of thyroid tissues were detected by VA. In vivo results showed 100% of US proven calcifications and 91% of the US detected nodules were identified by VA, however, some artifacts were present in some cases.
Conclusions
In vitro and in vivo VA images show promising results for delineating the detailed structure of the thyroid, finding nodules and in particular calcifications with greater clarity compare to US. Our findings suggest that, with further development, VA may be a suitable imaging modality for clinical thyroid imaging.
doi:10.1186/1471-2342-13-12
PMCID: PMC3618245  PMID: 23530993
Elasticity imaging techniques; Vibro-acoustography; Thyroid neoplasm; Thyroid nodule; Ultrasound; Imaging
22.  Loss tangent and complex modulus estimated by acoustic radiation force creep and shear wave dispersion 
Physics in Medicine and Biology  2012;57(5):1263-1282.
Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. In current shear wave elasticity imaging methods typically only shear wave speed is measured and rheological models, e.g., Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for tissue mechanical properties such as the shear viscoelastic complex modulus. This paper presents a method to quantify viscoelastic material properties in a model-independent way by estimating the complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. This radiation force induced creep (RFIC) method uses a conversion formula that is the analytic solution of a constitutive equation. The proposed method in combination with Shearwave Dispersion Ultrasound Vibrometry (SDUV) is used to measure the complex modulus so that knowledge of the applied radiation force magnitude is not necessary. The conversion formula is shown to be sensitive to sampling frequency and the first reliable measure in time according to numerical simulations using the Kelvin-Voigt model creep strain and compliance. Representative model-free shear complex moduli from homogeneous tissue mimicking phantoms and one excised swine kidney were obtained. This work proposes a novel model-free ultrasound-based elasticity method that does not require a rheological model with associated fitting requirements.
doi:10.1088/0031-9155/57/5/1263
PMCID: PMC3376913  PMID: 22345425
23.  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 (50–500 Hz). The motivation for developing elasticity imaging techniques is based on the possibility of diagnosing disease process. 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 SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity on healthy swine kidney. A total of eight excised kidneys from female pigs were used in these in vitro experiments, and a battery of different tests were performed to gain insight on the material properties of the renal cortex. From these eight kidneys, the overall renal cortex elasticity and viscosity was 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 hour 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. More than 30% increases in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Lastly, 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.
doi:10.1109/TUFFC.2011.2124
PMCID: PMC3588601  PMID: 23443697
24.  Bias Observed in Time-of-flight Shear Wave Speed Measurements Using Radiation Force of a Focused Ultrasound Beam 
Ultrasound in medicine & biology  2011;37(11):1884-1892.
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.
doi:10.1016/j.ultrasmedbio.2011.07.012
PMCID: PMC3199321  PMID: 21924817
Shear wave speed; Liver fibrosis; Bias; ARFI
25.  A Review of Vibro-acoustography and its Applications in Medicine 
Current medical imaging reviews  2011;7(4):350-359.
In recent years, several new techniques based on the radiation force of ultrasound have been developed. Vibro-acoustography is a speckle-free ultrasound based imaging modality that can visualize normal and abnormal soft tissue through mapping the acoustic response of the object to a harmonic radiation force induced by ultrasound. In vibro-acoustography, the ultrasound energy is converted from high ultrasound frequencies to a low acoustic frequency (acoustic emission) that is often two orders of magnitude smaller than the ultrasound frequency. The acoustic emission is normally detected by a hydrophone. In medical imaging, vibroacoustography has been tested on breast, prostate, arteries, liver, and thyroid. These studies have shown that vibro-acoustic data can be used for quantitative evaluation of elastic properties. This paper presents an overview of vibro-acoustography and its applications in the areas of biomedicine.
PMCID: PMC3298414  PMID: 22423235
Ultrasound; Radiation force; Vibro-acoustography; Imaging

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