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1.  Investigation of the Effects of Myocardial Anisotropy for Shear Wave Elastography using Impulsive Force and Harmonic Vibration 
Physics in medicine and biology  2015;61(1):365-382.
The myocardium is known to be an anisotropic medium where the muscle fiber orientation changes through the thickness of the wall. Shear wave elastography methods use propagating waves which are measured by ultrasound or magnetic resonance imaging (MRI) techniques to characterize the mechanical properties of various tissues. Ultrasound- or MR-based methods have been used and the excitation frequency ranges for these various methods cover a large range from 24-500 Hz. Some of the ultrasound-based methods have been shown to be able to estimate the fiber direction. We constructed a model with layers of elastic, transversely isotropic materials that were oriented at different angles to simulate the heart wall in systole and diastole. We investigated the effect of frequency on the wave propagation and the estimation of fiber direction and wave speeds in the different layers of the assembled models. We found that waves propagating at low frequencies such as 30 or 50 Hz showed low sensitivity to the fiber direction but also had substantial bias in estimating the wave speeds in the layers. Using waves with higher frequency content (> 200 Hz) allowed for more accurate fiber direction and wave speed estimation. These results have particular relevance for MR- and ultrasound-based elastography applications in the heart.
PMCID: PMC4816222  PMID: 26674613
anisotropy; transverse isotropy; shear wave; frequency; myocardium
2.  Simultaneous identification of elastic properties, thickness, and diameter of arteries excited with ultrasound radiation force 
Physics in medicine and biology  2015;60(13):5279-5296.
The elastic and geometric properties of arteries have been long recognized as important predictors of cardiovascular disease. This work presents a robust technique for the noninvasive characterization of anisotropic elastic properties as well as thickness and diameter in arterial vessels. In our approach, guided waves are excited along arteries using the radiation force of ultrasound. Group velocity is used as the quantity of interest to reconstruct elastic and geometric features of the vessels. One of the main contributions of this work is a systematic approach based on sparse-grid collocation interpolation to construct surrogate models of arteries. These surrogate models are in turn used with direct-search optimization techniques to produce fast and accurate estimates of elastic properties, diameter, and thickness. One of the attractive features of the proposed approach is that once a surrogate model is built, it can be used for near real-time identification across many different types of arteries. We demonstrate the feasibility of the method using simulated and in vitro laboratory experiments on a silicon rubber tube and a porcine carotid artery. Our results show that using our proposed method, we can reliably identify the longitudinal modulus, thickness, and diameter of arteries. The circumferential modulus was found to have little influence in the group velocity, which renders the former quantity unidentifiable using the current experimental setting. Future work will consider the measurement of circumferential waves with the objective of improving the identifiability of the circumferential modulus.
PMCID: PMC4520308  PMID: 26109582
3.  Characterization of Transverse Isotropy in Compressed Tissue Mimicking Phantoms 
Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest which makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested six phantoms made with different concentrations of gelatin and agar. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique. Autocorrelation was applied to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0–360°, where the stress is applied along 0–180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue mimicking phantom.
PMCID: PMC4431654  PMID: 26067038
shear wave; transverse isotropy; acoustoelasticity; stress
4.  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.
PMCID: PMC4400871  PMID: 25881343
5.  Superficial Ultrasound Shear Wave Speed Measurements in Soft and Hard Elasticity Phantoms: Repeatability and Reproducibility Using Two Different Ultrasound Systems 
Pediatric radiology  2014;45(3):376-385.
There is a paucity of data available regarding the repeatability and reproducibility of superficial shear wave speed (SWS) measurements at imaging depths relevant to the pediatric population.
To assess the repeatability and reproducibility of superficial shear wave speed (SWS) measurements acquired from elasticity phantoms at varying imaging depths using three different imaging methods, two different ultrasound systems, and multiple operators.
Methods and Materials
Soft and hard elasticity phantoms manufactured by Computerized Imaging Reference Systems, Inc. (Norfolk, VA) were utilized for our investigation. Institution #1 used an Acuson S3000 ultrasound system (Siemens Medical Solutions USA, Inc.) and three different shear wave imaging method/transducer combinations, while institution #2 used an Aixplorer ultrasound system (Supersonic Imagine) and two different transducers. Ten stiffness measurements were acquired from each phantom at three depths (1.0, 2.5, and 4.0 cm) by four operators at each institution. Student’s t-test was used to compare SWS measurements between imaging techniques, while SWS measurement agreement was assessed with two-way random effects single measure intra-class correlation coefficients and coefficients of variation. Mixed model regression analysis determined the effect of predictor variables on SWS measurements.
For the soft phantom, the average of mean SWS measurements across the various imaging methods and depths was 0.84 ± 0.04 m/s (mean ± standard deviation) for the Acuson S3000 system and 0.90 ± 0.02 m/s for the Aixplorer system (p=0.003). For the hard phantom, the average of mean SWS measurements across the various imaging methods and depths was 2.14 ± 0.08 m/s for the Acuson S3000 system and 2.07 ± 0.03 m/s Aixplorer system (p>0.05). The coefficients of variation were low (0.5–6.8%), and inter-operator agreement was near-perfect (ICCs ≥0.99). Shear wave imaging method and imaging depth significantly affected measured SWS (p<0.0001).
Superficial SWS measurements in elasticity phantoms demonstrate minimal variability across imaging method/transducer combinations, imaging depths, and between operators. The exact clinical significance of this variability is uncertain and may vary by organ and specific disease state.
PMCID: PMC4346477  PMID: 25249389
6.  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.
PMCID: PMC4314720  PMID: 25591921
transversely isotropic; viscoelastic; incompressible; finite element; shear wave; ultrasound elastography
7.  Complex Background Suppression for Vibro-acoustography Images 
Ultrasonics  2014;0:456-472.
Vibro-acoustography (VA) is an ultrasound-based imaging modality that maps the acoustic response, or acoustic emission, of an object stimulated by two ultrasound waves at slightly different frequencies. VA images typically have a nonzero background intensity which can reduce contrast in images. We present a method that uses the complex representation of the acoustic emission data to estimate and suppress the unwanted background signal. This method utilizes a fast, linear approach to the problem called complex background suppression (CBS) using a square filtering window of size W × W. Images processed with the CBS algorithm have significantly enhanced contrast. Another improvement observed with this method is the ability to better localize objects within the depth direction with respect to the ultrasound transducer. This algorithm was tested on images obtained from scanning a phantom with spherical inclusions, a urethane breast phantom, and in vivo human breast. The results show that image quality is improved through processing with the CBS algorithm by increasing the contrast of features in the images. The contrast in the sphere phantom was increased by factors of 2-12 depending on the sphere. Utilizing the CBS algorithm increased the contrast in breast phantom by factors ranging from 1.1-5.4 for various inclusions. The size of the filtering window, W, affected the contrast achieved between the phantom features such as the spheres or simulated inclusions and the background material. Application of the CBS algorithm also demonstrated that objects could be localized in depth much better as the relationship to image intensity level was directly correlated to objects located at the center of the focal plane in the axial direction. This method has wide applicability for all VA imaging applications.
PMCID: PMC4252849  PMID: 25304993
vibro-acoustography; complex; ultrasound; parametric mixing; background artifact; acoustic emission
8.  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.
PMCID: PMC4315508  PMID: 25643079
Shear wave elastography; acoustic radiation force; CUSE; LOGIQ E9
9.  Performance of 2-D ultrasound shear wave elastography in liver fibrosis detection using magnetic resonance elastography as the reference standard: A pilot study 
To investigate the correlation between 2-D ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2-D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard.
2-D SWE was performed on 47 patients (22 females and 25 males, age 19–77) using the GE LOGIQ E9 scanner. Each of the 47 patients had same day MRE obtained for clinical purposes. The study was HIPAA-compliant and approved by the institutional review board. Informed consent was obtained from each subject. 2-D SWE measurements were acquired from the 9th, 8th, and 7th intercostal spaces. Correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2-D SWE in diagnosing liver fibrosis was evaluated with receiver operating characteristic (ROC) curve analysis using MRE as the standard.
The highest correlation between 2-D SWE and MRE was from the 8th and 7th intercostal spaces (r = 0.68 – 0.76). The range of the areas under the ROC curve for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 – 0.92 when using 8th and 7th intercostal spaces individually, and 0.89 –0.9 when combined.
The results suggest that 2-D SWE and MRE are well correlated when SWE is performed at the 8th and 7th intercostal spaces. The 9th intercostal space is less reliable for diagnosing fibrosis using 2-D SWE. Combining measurements from multiple intercostal spaces does not significantly improve 2-D SWE performance for the detection of fibrosis.
PMCID: PMC4724277  PMID: 26782164
shear wave elastography; magnetic resonance elastography; liver fibrosis
10.  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.
PMCID: PMC4442078  PMID: 25419697
Transverse isotropy; Ultrasound; Acoustic radiation force; Phantoms; muscle; Shear wave imaging
11.  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.
PMCID: PMC4216646  PMID: 25020066
Directional filter; external vibration; liver fibrosis; magnetic resonance elastography; shear wave elastography; shear wave speed
12.  Noninvasive Assessment of Liver Fibrosis Using Ultrasound-based Shear Wave Measurement and Comparison to Magnetic Resonance Elastography 
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.
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 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).
Results indicate that the ultrasound shear wave measurement correlates with MRE and is a promising method for liver fibrosis staging.
PMCID: PMC4145616  PMID: 25154941
Ultrasound; Shear Wave; Liver fibrosis; MRE
13.  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.
PMCID: PMC4530976  PMID: 26168181
coded excitation; shear wave; elastography; Barker; chirp; shear wave detection
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.
PMCID: PMC4118646  PMID: 24814645
Echocardiography; Elasticity; Elastography; Myocardial stiffness; Myocardial infarction; Shear elasticity; Shear wave; Ultrasound; Viscoelasticity
15.  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.
PMCID: PMC4011964  PMID: 24613636
shear compounding; shear wave elastography; 2D shear wave speed; directional filter; comb-push; acoustic radiation force
16.  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.
PMCID: PMC3947393  PMID: 24021638
Harmonic imaging; shear wave elastography; acoustic radiation force; pulse inversion; in vivo human heart; transthoracic scanning; diastolic left ventricle stiffness
17.  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.
PMCID: PMC3849318  PMID: 24139918
shear wave; hybrid beamforming; axicon; shear wave speed; depth-of-field
18.  Ultrasound Vibrometry Using Orthogonal Frequency Based Vibration Pulses 
New vibration pulses are developed for shear wave generation in a tissue region with preferred spectral distributions for ultrasound vibrometry applications. The primary objective of this work is to increase the frequency range of detectable harmonics of the shear wave. The secondary objective is to reduce the required peak intensity of transmitted pulses that induce the vibrations and shear waves. Unlike the periodic binary vibration pulses, the new vibration pulses have multiple pulses in one fundamental period of the vibration. The pulses are generated from an orthogonal-frequency wave composed of several sinusoidal signals of which the amplitudes increase with frequency to compensate for higher loss at higher frequency in tissues. The new method has been evaluated by studying the shear wave propagation in in vitro chicken and swine liver. The experimental results show that the new vibration pulses significantly increase tissue vibration with a reduced peak ultrasound intensity, compared with the binary vibration pulses.
PMCID: PMC4122309  PMID: 24158291
Shear wave; ultrasound vibrometry; harmonic motion; elasticity; viscosity; viscoelasticity; SDUV; ultrasound radiation force; pulse echo ultrasound; orthogonal frequency
19.  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.
PMCID: PMC3760382  PMID: 23591479
CUSE; comb-push; ultrasound elastography; shear wave; acoustic radiation force; unfocused ultrasound beam; focused ultrasound beam
20.  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.
PMCID: PMC3682421  PMID: 23643056
compressional wave; shear wave; elasticity; viscoelasticity; acoustic imaging; dispersion; anisotropy
22.  A Beamforming Study for Implementation of Vibro-acoustography with a 1.75D Array Transducer 
Vibro-acoustography (VA) is an ultrasound-based imaging modality that uses radiation force produced by two cofocused ultrasound beams separated by a small frequency difference, Δf, to vibrate tissue at Δf. An acoustic field is created by the object vibration and measured with a nearby hydrophone. This method has recently been implemented on a clinical ultrasound system using one-dimensional (1D) linear array transducers. In this article, we discuss VA beamforming and image formation using a 1.75D array transducer. A 1.75D array transducer has several rows of elements in the elevation direction which can be controlled independently for focusing. The advantage of the 1.75D array over a 1D linear array transducer is that multiple rows of elements can be used for improving elevation focus for imaging formation. Six configurations for subaperture design for the two ultrasound beams necessary for VA imaging were analyzed. The point-spread functions for these different configurations were evaluated using a numerical simulation model. Four of these configurations were then chosen for experimental evaluation with a needle hydrophone as well as for scanning two phantoms. Images were formed by scanning a urethane breast phantom and an ex vivo human prostate. VA imaging using a 1.75D array transducer offers several advantages over scanning with a linear array transducer including improved image resolution and contrast due to better elevation focusing of the imaging point-spread function.
PMCID: PMC3610531  PMID: 23475919
23.  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.
PMCID: PMC3562367  PMID: 23060325
24.  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.
PMCID: PMC3413738  PMID: 22766123
Elasticity; Shear wave; Ultrasound radiation force; Unfocused
25.  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.
PMCID: PMC3475422  PMID: 22736690
comb-push; unfocused ultrasound beam; ultrasound elastography; acoustic radiation force; inclusion

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