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1.  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.
Background
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.
Purpose
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.
Results
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).
Conclusions
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.
doi:10.1007/s00247-014-3150-6
PMCID: PMC4346477  PMID: 25249389
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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

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