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Reliably detecting prostate cancer (PCa) has been a challenge for current imaging modalities. Acoustic radiation force impulse (ARFI) imaging is an elasticity imaging method that uses remotely generated, focused acoustic beams to probe tissue stiffness. A previous study on excised human prostates demonstrated ARFI images portray various prostatic structures and has the potential to guide prostate needle biopsy with improved sampling accuracy. The goal of this study is to demonstrate the feasibility of ARFI imaging to portray internal structures and PCa in the human prostate in vivo. Custom ARFI imaging sequences were designed and implemented using a modified Siemens Antares™ scanner with a three-dimensional (3-D) wobbler, end-firing, trans-cavity transducer, EV9F4. Nineteen patients were consented and imaged immediately preceding surgical prostatectomy. Pathologies and anatomic structures were identified in histologic slides by a pathologist blinded to ARFI data and were then registered with structures found in ARFI images. The results demonstrated that when PCa is visible, it generally appears as bilaterally asymmetric stiff structures; benign prostatic hyperplasia (BPH) appears heterogeneous with a nodular texture; the verumontanum and ejaculatory ducts appears softer compared with surrounding tissue, which form a unique 'V' shape; and the boundary of the transitional zone (TZ) forms a stiff rim separating the TZ from the peripheral zone (PZ). These characteristic appearances of prostatic structures are consistent with those found in our previous study of prostate ARFI imaging on excised human prostates. Compared with the matched B-mode images, ARFI images, in general, portray prostate structures with higher contrast. With the end-firing transducer used for this study, ARFI depth penetration was limited to 22 mm. Image contrast and resolution were decreased as compared with the previous ex vivo study due to the small transducer aperture. Even with these limitations, this study suggests ARFI imaging holds promise for guidance of targeted prostate needle biopsy and focal therapy, as well as aiding assessment of changes during watchful waiting/active surveillance. [ABSTRACT FROM AUTHOR]

We have developed a 3-D acoustic radiation force impulse (ARFI) prostate imaging system to identify regions suspicious for cancer and guide a targeted prostate biopsy in a single visit. The system uses a side-fire transrectal probe and an automated rotation stage to acquire ARFI and B-mode image volumes, combined with 3-D visualization and targeting software to enable biopsy target identification and guide a transperineal (TP) biopsy. The system was tested in the first clinical trial of its kind, with subjects serially undergoing ARFI-guided targeted TP biopsy, multiparametric magnetic resonance imaging (mpMRI)-ultrasound fusion TP biopsy, and systematic sampling TP biopsy. The findings indicate that the ARFI system is feasible for guiding a targeted biopsy. For lower-grade cancer (grade groups [GG] 1-2), ARFI underperformed mpMRI and systematic sampling, detecting cancer in 54% of GG 2 subjects. However, ARFI performance improved with increasing cancer grade; for higher-grade cancer (GG 3-5), ARFI performed comparably to the other biopsy approaches, and detected cancer in all GG 4 and 5 subjects. The findings also suggest the benefit of using 2-D ARFI imaging to confirm target location during live B-mode imaging, which could improve existing ultrasonic fusion biopsy workflows. This study is registered with ClinicalTrials.gov as NCT04607135., Competing Interests: Declaration of Conflicting InterestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K. R. Nightingale and M. L. Palmeri have intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems.

The stress-strain relation in a transversely isotropic (TI) material is described by five independent parameters. In the incompressible limit, only three parameters are required to describe shear wave propagation. Existing material parameterization models are not ideal for the analysis of wave propagation in the nearly incompressible TI (NITI) regime due to difficult-to-interpret parameters, complicated forms of the stiffness matrix elements, or the lack of five independent parameters. This study describes a new parameterization model for a general, TI material that uses the bulk modulus K, shear moduli μT and μL, a modulus-like term μE, and a new parameter η. In the proposed parameterization model, each parameter has a clear interpretation related to compressibility and shear wave propagation. The incompressible limit is represented by the limit K → ∞. Wave speeds and polarizations are derived and evaluated in both incompressible and NITI regimens. First-order NITI corrections are shown to be inversely proportional to the ratio of bulk modulus to shear moduli. In biological soft tissues, this ratio is approximately 106. NITI corrections depend on all five independent parameters; however, the small scale of these corrections validates previous studies that have assumed particular values for the parameter η., (© 2024 Acoustical Society of America.)

Objective: A deep neural network (DNN) was trained to generate a multiparametric ultrasound (mpUS) volume from four input ultrasound-based modalities (acoustic radiation force impulse [ARFI] imaging, shear wave elasticity imaging [SWEI], quantitative ultrasound-midband fit [QUS-MF], and B-mode) for the detection of prostate cancer., Methods: A DNN was trained using co-registered ARFI, SWEI, MF, and B-mode data obtained in men with biopsy-confirmed prostate cancer prior to radical prostatectomy (15 subjects, comprising 980,620 voxels). Data were obtained using a commercial scanner that was modified to allow user control of the acoustic beam sequences and provide access to the raw image data. For each subject, the index lesion and a non-cancerous region were manually segmented using visual confirmation based on whole-mount histopathology data., Results: In a prostate phantom, the DNN increased lesion contrast-to-noise ratio (CNR) compared to a previous approach that used a linear support vector machine (SVM). In the in vivo test datasets (n = 15), the DNN-based mpUS volumes clearly portrayed histopathology-confirmed prostate cancer and significantly improved CNR compared to the linear SVM (2.79 ± 0.88 vs. 1.98 ± 0.73, paired-sample t-test p < 0.001). In a sub-analysis in which the input modalities to the DNN were selectively omitted, the CNR decreased with fewer inputs; both stiffness- and echogenicity-based modalities were important contributors to the multiparametric model., Conclusion: The findings from this study indicate that a DNN can be optimized to generate mpUS prostate volumes with high CNR from ARFI, SWEI, MF, and B-mode and that this approach outperforms a linear SVM approach., Competing Interests: Conflict of interest K.R. Nightingale and M.L. Palmeri have intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The advent of high-frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart's thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave., Competing Interests: Funding Support and Author Disclosures This work was supported by the Research Foundation Flanders under grants 1211620N and 12B3124N to Dr Caenen and grant G092318N to Dr Bézy. Dr Voigt holds a personal research mandate of the Research Foundation Flanders (1832922N). Dr Nightingale has intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems. Dr Pernot has intellectual property related to SWE that has been licensed to eMyoSound. Dr Vos has an ongoing research collaboration with Mindray Ultrasound. Drs Voigt and Jan D’hooge have an ongoing research collaboration with GE Vingmed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Skeletal muscle is a complex tissue, exhibiting not only direction-dependent material properties (commonly modeled as a transversely isotropic material), but also changes in observed material properties due to factors such as contraction and passive stretch. In this work, we evaluated the effect of muscle passive stretch on shear wave propagation along and across the muscle fibers using a rotational 3D shear wave elasticity imaging system and automatic analysis methods. We imaged the vastus lateralis of 10 healthy volunteers, modulating passive stretch by imaging at 8 different knee flexion angles (controlled by a BioDex system). In addition to demonstrating the ability of this acquisition and automatic processing system to estimate muscle shear moduli over a range of values, we evaluated potential higher order biomarkers for muscle health that capture the change in muscle stiffness along and across the fibers with changing knee flexion. The median within-subject variability of these biomarkers is found to be <16%, suggesting promise as a repeatable clinical metric. Additionally, we report an unexpected observation: that shear wave signal amplitude along the fibers increases with increasing flexion and muscle stiffness, which is not predicted by transversely isotropic (TI) material simulations. This observation may point to an additional potential biomarker for muscle health or inform other material modeling choices for muscle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study demonstrates the implementation of a shear wave reconstruction algorithm that enables concurrent acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) of prostate cancer and zonal anatomy. The combined ARFI/SWEI sequence uses closely spaced push beams across the lateral field of view and simultaneously tracks both on-axis (within the region of excitation) and off-axis (laterally offset from the excitation) after each push beam. Using a large number of push beams across the lateral field of view enables the collection of higher signal-to-noise ratio (SNR) shear wave data to reconstruct the SWEI volume than is typically acquired. The shear wave arrival times were determined with cross-correlation of shear wave velocity signals in two dimensions after 3-D directional filtering to remove reflection artifacts. To combine data from serially interrogated lateral push locations, arrival times from different pushes were aligned by estimating the shear wave propagation time between push locations. Shear wave data acquired in an elasticity lesion phantom and reconstructed using this algorithm demonstrate benefits to contrast-to-noise ratio (CNR) with increased push beam density and 3-D directional filtering. Increasing the push beam spacing from 0.3 to 11.6 mm (typical for commercial SWEI systems) resulted in a 53% decrease in CNR. In human in vivo data, this imaging approach enabled high CNR (1.61-1.86) imaging of histologically-confirmed prostate cancer. The in vivo images had improved spatial resolution and CNR and fewer reflection artifacts as a result of the high push beam density, the high shear wave SNR, the use of multidimensional directional filtering, and the combination of shear wave data from different push beams.

Shear wave elasticity imaging (SWEI) usually assumes an isotropic material; however, skeletal muscle is typically modeled as a transversely isotropic material with independent shear wave speeds in the directions along and across the muscle fibers. To capture these direction-dependent properties, we implemented a rotational 3-D SWEI system that measures the shear wave speed both along and across the fibers in a single 3-D acquisition, with automatic detection of the muscle fiber orientation. We tested and examined the repeatability of this system's measurements in the vastus lateralis of 10 healthy volunteers. The average coefficient of variation of the measurements from this 3-D SWEI system was 5.3% along the fibers and 8.1% across the fibers. When compared with estimated respective 2-D SWEI values of 16.0% and 83.4%, these results suggest using 3-D SWEI has the potential to improve the precision of SWEI measurements in muscle. Additionally, we observed no significant difference in shear wave speed between the dominant and non-dominant legs along (p = 0.26) or across (p = 0.65) the muscle fibers., Competing Interests: Conflict of interest disclosure Kathryn Nightingale and Mark Palmeri have intellectual property relating to radiation force-based imaging technologies that has been licensed to Siemens, Samsung and Micro Elastic Ultrasound Systems., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

In the context of ultrasonic hepatic shear wave elasticity imaging (SWEI), measurement success has been determined to increase when using elevated acoustic output pressures. As SWEI sequences consist of two distinct operations (pushing and tracking), acquisition failures could be attributed to (i) insufficient acoustic radiation force generation resulting in inadequate shear wave amplitude and/or (ii) distorted ultrasonic tissue motion tracking. In the study described here, an opposing window experimental setup that isolated body wall effects separately between the push and track SWEI operations was implemented. A commonly employed commercial track configuration was used, harmonic multiple-track-location SWEI. The effects of imaging through body walls on the pushing and tracking operations of SWEI as a function of mechanical index (MI), spanning 5 different push beam MIs and 10 track beam MIs, were independently assessed using porcine body walls. Shear wave speed yield was found to increase with both increasing push and track MI. Although not consistent across all samples, measurements in a subset of body walls were found to be signal limited during tracking and to increase yield by up to 35% when increasing electronic signal-to-noise ratio by increasing harmonic track transmit pressure., Competing Interests: Conflict of interest disclosure K.R.N. has intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung and MicroElastic Ultrasound Systems., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasonic rotational 3-D shear wave elasticity imaging (SWEI) has been used to induce and evaluate multiple shear wave modes, including both the shear horizontal (SH) and shear vertical (SV) modes in in vivo muscle. Observations of both the SH and SV modes allow the muscle to be characterized as an elastic, incompressible, transversely isotropic (ITI) material with three parameters: the longitudinal shear modulus μ L , the transverse shear modulus μ T , and the tensile anisotropy χ E . Measurement of the SV wave is necessary to characterize χ E , but the factors that influence SV mode generation and characterization with ultrasonic SWEI are complicated. This work uses Green's function (GF) simulations to perform a parametric analysis to determine the optimal interrogation parameters to facilitate visualization and quantification of SV mode shear waves in muscle. We evaluate the impact of five factors: μ L , μ T , χ E , fiber tilt angle [Formula: see text], and F-number of the push geometry on SV mode speed, amplitude, and rotational distribution. These analyses demonstrate that the following hold: 1) as μ L increases, SV waves decrease in amplitude so are more difficult to measure in SWEI imaging; 2) as μ T increases, the SV wave speeds increase; 3) as χ E increases, the SV waves increase in speed and separate from the SH waves; 4) as fiber tilt angle [Formula: see text] increases, the measurable SV waves remain approximately the same speed, but change in strength and in rotational distribution; and 5) as the push beam geometry changes with F-number, the measurable SV waves remain approximately the same speed, but change in strength and rotational distribution. While specific SV mode speeds depend on the combinations of all parameters considered, measurable SV waves can be generated and characterized across the range of parameters considered. To maximize measurable SV waves separate from the SH waves, it is recommended to use an F/1 push geometry and [Formula: see text].

Ultrasound monitoring, both in the form of Doppler and 2D echocardiography, has been used post-dive to detect decompression bubbles circulating in the bloodstream. With large variability in both bubble time course and loads, it has been hypothesised that shorter periods between imaging, or even continuous imaging, could provide more accurate post-dive assessments. However, while considering applications of ultrasound imaging post-decompression, it may also be prudent to consider the possibility of ultrasound-induced bioeffects. Clinical ultrasound studies using microbubble contrast agents have shown bioeffect generation with acoustic powers much lower than those used in post-dive monitoring. However, to date no studies have specifically investigated potential bioeffect generation from continuous post-dive echocardiography. This review discusses what can be drawn from the current ultrasound and diving literature on the safety of bubble sonication and highlights areas where more studies are needed. An overview of the ultrasound-bubble mechanisms that lead to bioeffects and analyses of ultrasound contrast agent studies on bioeffect generation in the pulmonary and cardiovascular systems are provided to illustrate how bubbles under ultrasound can cause damage within the body. Along with clinical ultrasound studies, studies investigating the effects of decompression bubbles under ultrasound are analysed and open questions regarding continuous post-dive monitoring safety are discussed., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Objective. Determining elastic properties of materials from observations of shear wave propagation is difficult in anisotropic materials because of the complex relations among the propagation direction, shear wave polarizations, and material symmetries. In this study, we derive expressions for the phase velocities of the SH and SV propagation modes as a function of propagation direction in an incompressible, hyperelastic material with uniaxial stretch. Approach. Wave motion is included in the material model by adding incremental, small amplitude motion to the initial, finite deformation. Equations of motion for the SH and SV propagation modes are constructed using the Cauchy stress tensor derived from the strain energy function of the material. Group velocities for the SH and SV propagation modes are derived from the angle-dependent phase velocities. Main results. Sample results are presented for the Arruda-Boyce, Mooney-Rivlin, and Isihara material models using model parameters previously determined in a phantom. Significance. Results for the Mooney-Rivlin and Isihara models demonstrate shear splitting in which the SH and SV propagation modes have unequal group velocities for propagation across the material symmetry axis. In addition, for sufficiently large stretch, the Arruda-Boyce and Isihara material models show cusp structures with triple-valued group velocities for the SV mode at angles of roughly 15° to the material symmetry axis., (© 2022 Institute of Physics and Engineering in Medicine.)

Shear wave elastography offers a new dimension to echocardiography: it measures myocardial stiffness. Therefore, it could provide additional insights into the pathophysiology of cardiac diseases affecting myocardial stiffness and potentially improve diagnosis or guide patient treatment. The technique detects fast mechanical waves on the heart wall with high frame rate echography, and converts their propagation speed into a stiffness value. A proper interpretation of shear wave data is required as the shear wave interacts with the intrinsic, yet dynamically changing geometrical and material characteristics of the heart under pressure. This dramatically alters the wave physics of the propagating wave, demanding adapted processing methods compared to other shear wave elastography applications as breast tumor and liver stiffness staging. Furthermore, several advanced analysis methods have been proposed to extract supplementary material features such as viscosity and anisotropy, potentially offering additional diagnostic value. This review explains the general mechanical concepts underlying cardiac shear wave elastography and provides an overview of the preclinical and clinical studies within the field. We also identify the mechanical and technical challenges ahead to make shear wave elastography a valuable tool for clinical practice., (© 2022 Institute of Physics and Engineering in Medicine.)

Using a 3D rotational shear wave elasticity imaging (SWEI) setup, 3D shear wave data were acquired in the vastus lateralis of a healthy volunteer. The innate tilt between the transducer face and the muscle fibers results in the excitation of multiple shear wave modes, allowing for more complete characterization of muscle as an elastic, incompressible, transversely isotropic (ITI) material. The ability to measure both the shear vertical (SV) and shear horizontal (SH) wave speed allows for measurement of three independent parameters needed for full ITI material characterization: the longitudinal shear modulus μ L , the transverse shear modulus μ T , and the tensile anisotropy χ E . Herein we develop and validate methodology to estimate these parameters and measure them in vivo, with μ L = 5.77±1.00 kPa, μ T = 1.93±0.41 kPa (giving shear anisotropy χ μ = 2.11±0.92 ), and χ E = 4.67±1.40 in a relaxed vastus lateralis muscle. We also demonstrate that 3D SWEI can be used to more accurately characterize muscle mechanical properties as compared to 2D SWEI.

Five material parameters are required to describe a transversely isotropic (TI) material including two Poisson's ratios that characterize the compressibility of the material. Both Poisson's ratios must be specified to model an incompressible, TI (ITI) material. However, a previous analysis of the procedure used to evaluate the incompressible limit in a two-dimensional (2D) space of Poisson's ratios has shown that elements of the stiffness tensor are not unique in this limit, and that an additional, fourth parameter is required to model these elements for an ITI material. In this study, we extend this analysis to the case of shear wave propagation in an ITI material. Shear wave signals are modeled using analytic Green's tensor methods to express the signals in terms of the phase velocity and polarization vectors of the shear horizontal (SH) and shear vertical (SV) propagation modes. In contrast to the previous result, the current analysis demonstrates that the phase velocity and polarization vectors are independent of the procedure used to evaluate the 2D limit of Poisson's ratios without the need to include an additional parameter. Thus, calculated shear wave signals are unique and can be used for comparison with experimental measurements to determine all three model parameters that characterize an ITI material., (© 2021 Institute of Physics and Engineering in Medicine.)

Tissue harmonic signal quality has been shown to improve with elevated acoustic pressure. The peak rarefaction pressure (PRP) for a given transmit, however, is limited by the Food and Drug Administration guidelines for mechanical index. We have previously demonstrated that the mechanical index overestimates in situ PRP for tightly focused beams in vivo, due primarily to phase aberration. In this study, we evaluate two spatial coherence-based image quality metrics-short-lag spatial coherence and harmonic short-lag spatial coherence-as proxy estimates for phase aberration and assess their correlation with in situ PRP in simulations and experiments when imaging through abdominal body walls. We demonstrate strong correlation between both spatial coherence-based metrics and in situ PRP (R 2  = 0.77 for harmonic short-lag spatial coherence, R 2  = 0.67 for short-lag spatial coherence), an observation that could be leveraged in the future for patient-specific selection of acoustic output., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasound elasticity imaging in soft tissue with acoustic radiation force requires the estimation of displacements, typically on the order of several microns, from serially acquired raw data A-lines. In this work, we implement a fully convolutional neural network (CNN) for ultrasound displacement estimation. We present a novel method for generating ultrasound training data, in which synthetic 3-D displacement volumes with a combination of randomly seeded ellipsoids are created and used to displace scatterers, from which simulated ultrasonic imaging is performed using Field II. Network performance was tested on these virtual displacement volumes, as well as an experimental ARFI phantom data set and a human in vivo prostate ARFI data set. In the simulated data, the proposed neural network performed comparably to Loupas's algorithm, a conventional phase-based displacement estimation algorithm; the rms error was [Formula: see text] for the CNN and 0.73 [Formula: see text] for Loupas. Similarly, in the phantom data, the contrast-to-noise ratio (CNR) of a stiff inclusion was 2.27 for the CNN-estimated image and 2.21 for the Loupas-estimated image. Applying the trained network to in vivo data enabled the visualization of prostate cancer and prostate anatomy. The proposed training method provided 26 000 training cases, which allowed robust network training. The CNN had a computation time that was comparable to Loupas's algorithm; further refinements to the network architecture may provide an improvement in the computation time. We conclude that deep neural network-based displacement estimation from ultrasonic data is feasible, providing comparable performance with respect to both accuracy and speed compared to current standard time-delay estimation approaches.

Transrectal ultrasound (TRUS) B-mode imaging provides insufficient sensitivity and specificity for prostate cancer (PCa) targeting when used for biopsy guidance. Shear wave elasticity imaging (SWEI) is an elasticity imaging technique that has been commercially implemented and is sensitive and specific for PCa. We have developed a SWEI system capable of 3-D data acquisition using a dense acoustic radiation force (ARF) push approach that leads to enhanced shear wave signal-to-noise ratio compared with that of the commercially available SWEI systems and facilitates screening of the entire gland before biopsy. Additionally, we imaged and assessed 36 patients undergoing radical prostatectomy using 3-D SWEI and determined a shear wave speed threshold separating PCa from healthy prostate tissue with sensitivities and specificities akin to those for multiparametric magnetic resonance imaging fusion biopsy. The approach measured the mean shear wave speed in each prostate region to be 4.8 m/s (Young's modulus E = 69.1 kPa) in the peripheral zone, 5.3 m/s (E = 84.3 kPa) in the central gland and 6.0 m/s (E = 108.0 kPa) for PCa with statistically significant (p < 0.0001) differences among all regions. Three-dimensional SWEI receiver operating characteristic analyses identified a threshold of 5.6 m/s (E = 94.1 kPa) to separate PCa from healthy tissue with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of 81%, 82%, 69%, 89% and 0.84, respectively. Additionally, a shear wave speed ratio was assessed to normalize for tissue compression and patient variability, which yielded a threshold of 1.11 to separate PCa from healthy prostate tissue and was accompanied by a substantial increase in specificity, PPV and AUC, where the sensitivity, specificity, PPV, NPV and AUC were 75%, 90%, 79%, 88% and 0.90, respectively. This work illustrates the feasibility of using 3-D SWEI data to detect and localize PCa and demonstrates the benefits of normalizing for applied compression during data acquisition for use in biopsy targeting studies., Competing Interests: Conflict of interest disclosure K.R.N. and M.L.P. have intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung and MicroElastic Ultrasound Systems., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Correctly calculating skin stiffness with ultrasound shear wave elastography techniques requires an accurate measurement of skin thickness. We developed and compared two algorithms, a thresholding method and a deep learning method, to measure skin thickness on ultrasound images. Here, we also present a framework for weakly annotating an unlabeled dataset in a time-effective manner to train the deep neural network. Segmentation labels for training were proposed using the thresholding method and validated with visual inspection by a human expert reader. We reduced decision ambiguity by only inspecting segmentations at the center A-line. This weak annotation approach facilitated validation of over 1000 segmentation labels in 2 hours. A lightweight deep neural network that segments entire 2D images was designed and trained on this weakly-labeled dataset. Averaged over six folds of cross-validation, segmentation accuracy was 57% for the thresholding method and 78% for the neural network. In particular, the network was better at finding the distal skin margin, which is the primary challenge for skin segmentation. Both algorithms have been made publicly available to aid future applications in skin characterization and elastography.

In this study, 3-D non-linear ultrasound simulations and experimental measurements were used to estimate the range of in situ pressures that can occur during transcutaneous abdominal imaging and to identify the sources of error when estimating in situ peak rarefaction pressures (PRPs) using linear derating, as specified by the mechanical index (MI) guideline. Using simulations, it was found that, for a large transmit aperture (F/1.5), MI consistently over-estimated in situ PRP by 20%-48% primarily owing to phase aberration. For a medium transmit aperture (F/3), the MI accurately estimated the in situ PRP to within 8%. For a small transmit aperture (F/5), MI consistently underestimated the in situ PRP by 32%-50%, with peak locations occurring 1-2 cm before the focal depth, often within the body wall itself. The large variability across body wall samples and focal configurations demonstrates the limitations of the simplified linear derating scheme. The results suggest that patient-specific in situ PRP estimation would allow for increases in transmit pressures, particularly for tightly focused beams, to improve diagnostic image quality while ensuring patient safety., Competing Interests: Conflict of Interest Author K. Nightingale has intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms., Methods: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz., Results: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source., Conclusions: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms., (© 2021 American Institute of Ultrasound in Medicine.)

Diagnosing prostate cancer through standard transrectal ultrasound (TRUS)-guided biopsy is challenging because of the sensitivity and specificity limitations of B-mode imaging. We used a linear support vector machine (SVM) to combine standard TRUS imaging data with acoustic radiation force impulse (ARFI) imaging data, shear wave elasticity imaging (SWEI) data and quantitative ultrasound (QUS) midband fit data to enhance lesion contrast into a synthesized multiparametric ultrasound volume. This SVM was trained and validated using a subset of 20 patients and tested on a second subset of 10 patients. Multiparametric US led to a statistically significant improvements in contrast, contrast-to-noise ratio (CNR) and generalized CNR (gCNR) when compared with standard TRUS B-mode and SWEI; in contrast and CNR when compared with MF; and in CNR when compared with ARFI. ARFI, MF and SWEI also outperformed TRUS B-mode in contrast, with MF outperforming B-mode in CNR and gCNR as well. ARFI, although only yielding statistically significant differences in contrast compared with TRUS B-mode, captured critical qualitative features for lesion identification. Multiparametric US enhanced lesion visibility metrics and is a promising technique for targeted TRUS-guided prostate biopsy in the future., Competing Interests: Conflict of interest disclosure K.R.N. and M.L.P. have intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung and MicroElastic Ultrasound Systems., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Tissue nonlinearity is conventionally measured in shear wave elastography by studying the change in wave speed caused by the tissue deformation, generally known as the acoustoelastic effect. However, these measurements have mainly focused on the excitation and detection of one specific shear mode, while it is theoretically known that the analysis of multiple wave modes offers more information about tissue material properties that can potentially be used to refine disease diagnosis. This work demonstrated proof of concept using experiments and finite element simulations in a uniaxially stretched phantom by tilting the acoustic radiation force excitation axis with respect to the material's symmetry axis. Using this unique set-up, we were able to visualize two propagating shear wave modes across the stretch direction for stretches larger than 140%. Complementary simulations were performed using material parameters determined from mechanical testing, which enabled us to convert the observed shear wave behavior into a correct representative constitutive law for the phantom material, i.e. the Isihara model. This demonstrates the potential of measuring shear wave propagation in combination with shear wave modeling in complex materials as a non-invasive alternative for mechanical testing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Some of the authors have intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This work discusses challenges we have encountered in acquiring reproducible measurements of shear wave speed (SWS) in the median nerve and suggests methods for improving reproducibility. First, procedural acquisition challenges are described, including nerve echogenicity, transducer pressure and transmit focal depth. Second, we present an iterative, radon sum-based algorithm that was developed specifically for measuring the SWS in median nerves. SWSs were measured using single track location shear wave elasticity imaging (SWEI) in the median nerves of six healthy volunteers and six patients diagnosed with carpal tunnel syndrome. Unsuccessful measurements were associated with several challenges including reverberation artifacts, low signal-to-noise ratio and temporal window limitations for tracking the velocity wave. To address these challenges, an iterative convergence algorithm was implemented to identify an appropriate temporal processing window that removed the reverberation artifacts while preserving shear wave signals. Algorithmically, it was important to consider the lateral regression kernel size and position and the temporal window. Procedurally, both nerve echogenicity and transducer compression were determined to impact the measured SWS. Shear waves were successfully measured in the median nerve proximal to the carpal tunnel, but SWEI measurements were significantly compromised within the carpal tunnel itself. The velocity-based SWSs were statistically significantly higher than the displacement SWSs (p < 0.0001), demonstrating for the first time dispersion in the median nerve in vivo using SWEI., Competing Interests: Conflict of interest disclosure The authors have no conflict of interest to disclose., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

While ultrasound shear wave elastography originally focused on tissue stiffness under the assumption of elasticity, recent work has investigated the higher order, viscoelastic properties of the tissue. This article presents a method to use group shear wave speeds (gSWSs) at a series of derivative orders to characterize viscoelastic materials. This method uses a least squares fitting algorithm to match the experimental data to the calculated gSWS data, using an assumed material model and excitation geometry matched to the experimental imaging configuration. Building on a previous study that used particle displacement, velocity, and acceleration signals, this study extends the analysis to a continuous range of fractional derivative orders between 0 and 2. The method can be applied to any material model. Herein, material characterization was performed for three different two-parameter models and three different three-parameter models. This group speed-based method was applied to both shear wave simulations with ultrasonic tracking and experimental acquisitions in viscoelastic phantoms [similar to the Phase II Quantitative Imaging Biomarkers Alliance (QIBA) phantoms]. In both the cases, the group speed method produced more repeatable characterization overall than fitting the phase velocity results from the peak of the 2-D Fourier transform. Results suggest that the linear attenuation model is a better fit than the Voigt model for the viscoelastic QIBA phantoms.

Assessing material properties from observations of shear wave propagation following an acoustic radiation force impulse (ARFI) excitation is difficult in anisotropic materials because of the complex relations among the propagation direction, shear wave polarizations, and material symmetries. In this paper, we describe a method to calculate shear wave signals using Green's tensor methods in an incompressible, transversely isotropic (TI) material characterized by three material parameters. The Green's tensor is written as the sum of an analytic expression for the SH propagation mode, and an integral expression for the SV propagation mode that can be evaluated by interpolation within precomputed integral functions with an efficiency comparable to the evaluation of a closed-form expression. By using parametrized integral functions, the number of required numerical integrations is reduced by a factor of 10 2 -10 9 depending on the specific problem under consideration. Results are presented for the case of a point source positioned at the origin and a tall Gaussian source similar to an ARFI excitation. For an experimental configuration with a tilted material symmetry axis, results show that shear wave signals exhibit structures that are sufficiently complex to allow measurement of all three material parameters that characterize an incompressible, TI material.

Recent investigations of viscoelastic properties of materials have been performed by observing shear wave propagation following localized, impulsive excitations, and Fourier decomposing the shear wave signal to parameterize the frequency-dependent phase velocity using a material model. This paper describes a new method to characterize viscoelastic materials using group shear wave speeds , , and determined from the shear wave displacement, velocity, and acceleration signals, respectively. Materials are modeled using a two-parameter linear attenuation model with phase velocity and dispersion slope at a reference frequency of 200 Hz. Analytically calculated lookup tables are used to determine the two material parameters from pairs of measured group shear wave speeds. Green's function calculations are used to validate the analytic model. Results are reported for measurements in viscoelastic and approximately elastic phantoms and demonstrate good agreement with phase velocities measured using Fourier analysis of the measured shear wave signals. The calculated lookup tables are relatively insensitive to the excitation configuration. While many commercial shear wave elasticity imaging systems report group shear wave speeds as the measures of material stiffness, this paper demonstrates that differences , , and of group speeds are first-order measures of the viscous properties of materials.

Shear wave elasticity imaging (SWEI) characterizes the mechanical properties of human tissues to differentiate healthy from diseased tissue. Commercial scanners tend to reconstruct shear wave speeds for a region of interest using time-of-flight methods reporting a single shear wave speed (or elastic modulus) to the end user under the assumptions that tissue is elastic and shear wave speeds are not dependent on the frequency content of the shear waves. Human tissues, however, are known to be viscoelastic, resulting in dispersion and attenuation. Shear wave spectroscopy and spectral methods have been previously reported in the literature to quantify shear wave dispersion and attenuation, commonly making an assumption that the acoustic radiation force excitation acts as a cylindrical source with a known geometric shear wave amplitude decay. This work quantifies the bias in shear dispersion and attenuation estimates associated with making this cylindrical wave assumption when applied to shear wave sources with finite depth extents, as commonly occurs with realistic focal geometries, in elastic and viscoelastic media. Bias is quantified using analytically derived shear wave data and shear wave data generated using finite-element method models. Shear wave dispersion and attenuation bias (up to 15% for dispersion and 41% for attenuation) is greater for more tightly focused acoustic radiation force sources with smaller depths of field relative to their lateral extent (height-to-width ratios <16). Dispersion and attenuation errors associated with assuming a cylindrical geometric shear wave decay in SWEI can be appreciable and should be considered when analyzing the viscoelastic properties of tissues with acoustic radiation force source distributions with limited depths of field., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Harmonic imaging techniques have been applied in ultrasonic elasticity imaging to obtain higher-quality tissue motion tracking data. However, harmonic tracking can be signal-to-noise ratio and penetration depth limited during clinical imaging, resulting in decreased yield of successful shear wave speed measurements. A logical approach is to increase the source pressure, but the in situ pressures used in diagnostic ultrasound have been subject to a de facto upper limit based on the Food and Drug Administration guideline for the mechanical index (MI <1.9). A recent American Institute of Ultrasound in Medicine report concluded that an in situ MI up to 4.0 could be warranted without concern for increased risk of cavitation in non-fetal tissues without gas bodies if there were a concurrent clinical benefit. This work evaluates the impact of using an elevated MI in harmonic motion tracking for hepatic shear wave elasticity imaging. The studies indicate that high-MI harmonic tracking increased shear wave speed estimation yield by 27% at a focal depth of 5 cm, with larger yield increase in more difficult-to-image patients. High-MI tracking improved harmonic tracking data quality by increasing the signal-to-noise ratio and decreasing jitter in the tissue motion data. We conclude that there is clinical benefit to use of elevated acoustic output in shear wave tracking, particularly in difficult-to-image patients., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Tissue harmonic imaging has been widely used in abdominal imaging because of its significant reduction in acoustic noise compared with fundamental imaging. However, tissue harmonic imaging can be limited by both signal-to-noise ratio and penetration depth during clinical imaging, resulting in decreased diagnostic utility. A logical approach would be to increase the source pressure, but the in situ pressures used in diagnostic ultrasound are subject to a de facto upper limit based on the U.S. Food and Drug Administration guideline for the mechanical index (<1.9). A recent American Institute of Ultrasound in Medicine report concluded that an effective mechanical index ≤4.0 could be warranted without concern for increased risk of cavitation in non-fetal tissues without gas bodies, but would only be justified if there were a concurrent improvement in image quality and diagnostic utility. This work evaluates image quality differences between normal and elevated acoustic output hepatic harmonic imaging using a transmit frequency of 1.8 MHz. The results indicate that harmonic imaging using elevated acoustic output leads to modest improvements (3%-7%) in contrast-to-noise ratio of hypo-echoic hepatic vessels and increases in imaging penetration depth on the order of 4 mm per mechanical index increase of 0.1 for a given focal depth. Difficult-to-image patients who suffer from poor ultrasound image quality exhibited larger improvements than easy-to-image study participants., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Recent measurements of shear wave propagation in viscoelastic materials have been analyzed by constructing the 2-D Fourier transform (2DFT) of the shear wave signal and measuring the phase velocity c(ω) and attenuation α(ω) from the peak location and full width at half-maximum (FWHM) of the 2DFT signal at discrete frequencies. However, when the shear wave is observed over a finite spatial range, the 2DFT signal is a convolution of the true signal and the observation window, and measurements using the FWHM can yield biased results. In this study, we describe a method to account for the size of the spatial observation window using a model of the 2DFT signal and a non-linear, least-squares fitting procedure to determine c(ω) and α(ω). Results from the analysis of finite-element simulation data agree with c(ω) and α(ω) calculated from the material parameters used in the simulation. Results obtained in a viscoelastic phantom indicate that the measured attenuation is independent of the observation window and agree with measurements of c(ω) and α(ω) obtained using the previously described progressive phase and exponential decay analysis., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasound elasticity imaging has been developed over the last decade to estimate tissue stiffness. Shear wave elasticity imaging (SWEI) quantifies tissue stiffness by measuring the speed of propagating shear waves following acoustic radiation force excitation. This paper presents the sequencing and data processing protocols of SWEI using a Verasonics system. The selection of the sequence parameters in a Verasonics programming script is discussed in detail. The data processing pipeline to calculate group shear wave speed (SWS), including tissue motion estimation, data filtering, and SWS estimation, is demonstrated. In addition, the procedures for calibration of beam position, scanner timing, and transducer face heating are provided to avoid SWS measurement bias and transducer damage.

Shear waves propagating through interfaces where there is a change in stiffness cause reflected waves that can lead to artifacts in shear wave speed (SWS) reconstructions. Two-dimensional (2-D) directional filters are commonly used to reduce in-plane reflected waves; however, SWS artifacts arise from both in- and out-of-imaging-plane reflected waves. Herein, we introduce 3-D shear wave reconstruction methods as an extension of the previous 2-D estimation methods and quantify the reduction in image artifacts through the use of volumetric SWS monitoring and 4-D-directional filters. A Gaussian acoustic radiation force impulse excitation was simulated in phantoms with Young's modulus ( E ) of 3 kPa and a 5-mm spherical lesion with E = 6, 12, or 18.75 kPa. The 2-D-, 3-D-, and 4-D-directional filters were applied to the displacement profiles to reduce in-and out-of-plane reflected wave artifacts. Contrast-to-noise ratio and SWS bias within the lesion were calculated for each reconstructed SWS image to evaluate the image quality. For 2-D SWS image reconstructions, the 3-D-directional filters showed greater improvements in image quality than the 2-D filters, and the 4-D-directional filters showed marginal improvement over the 3-D filters. Although 4-D-directional filters can further reduce the impact of large magnitude out-of-plane reflection artifacts in SWS images, computational overhead and transducer costs to acquire 3-D data may outweigh the modest improvements in image quality. The 4-D-directional filters have the largest impact in reducing reflection artifacts in 3-D SWS volumes.

Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Ultrasonic quantitative shear-wave imaging methods have been developed over the last decade to estimate tissue elasticity by measuring the speed of propagating shear waves following acoustic radiation force excitation. This work discusses eight sources of uncertainty and bias arising from ultrasound system-dependent parameters in ultrasound shear-wave speed (SWS) measurements. Each of the eight sources of error is discussed in the context of a linear, isotropic, elastic, homogeneous medium, combining previously reported analyses with Field II simulations, full-wave 2-D acoustic propagation simulations, and experimental studies. Errors arising from both spatial and temporal sources lead to errors in SWS measurements. Arrival time estimation noise, speckle bias, hardware fluctuations, and phase aberration cause uncertainties (variance) in SWS measurements, while pulse repetition frequency (PRF) and beamforming errors, as well as coupling medium sound speed mismatch, cause biases in SWS measurements (accuracy errors). Calibration of the sources of bias is an important step in the development of shear-wave imaging systems. In a well-calibrated system, where the sources of bias are minimized, and averaging over a region of interest (ROI) is employed to reduce the sources of uncertainty, an SWS error can be expected.

Recent measurements of shear wave propagation in viscoelastic materials have been analyzed by constructing the two-dimensional Fourier transform (2D-FT) of the spatial-temporal shear wave signal and using an analysis procedure derived under the assumption the wave is described as a plane wave, or as the asymptotic form of a wave expanding radially from a cylindrically symmetric source. This study presents an exact, analytic expression for the 2D-FT description of shear wave propagation in viscoelastic materials following asymmetric Gaussian excitations and uses this expression to evaluate the bias in 2D-FT measurements obtained using the plane or cylindrical wave assumptions. A wide range of biases are observed depending on specific values of frequency, aspect ratio R of the source asymmetry, and material properties. These biases can be reduced significantly by weighting the shear wave signal in the spatial domain to correct for the geometric spreading of the shear wavefront using a factor of x(p). The optimal weighting power p is found to be near the theoretical value of 0.5 for the case of a cylindrical source with R = 1, and decreases for asymmetric sources with R > 1.

The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues., (© 2015 by the American Institute of Ultrasound in Medicine.)

Shear wave elasticity imaging (SWEI) has found success in liver fibrosis staging. This work evaluates hepatic SWEI measurement success as a function of push pulse energy using two mechanical index (MI) values (1.6 and 2.2) over a range of pulse durations. Shear wave speed (SWS) was measured in the livers of 26 study subjects with known or potential chronic liver diseases. Each measurement consisted of eight SWEI sequences, each with different push energy configurations. The rate of successful SWS estimation was linearly proportional to the push energy. SWEI measurements with higher push energy were successful in patients for whom standard push energy levels failed. The findings also suggest that liver capsule depth could be used prospectively to identify patients who would benefit from elevated output. We conclude that there is clinical benefit to using elevated acoustic output for hepatic SWS measurement in patients with deeper livers., (Published by Elsevier Inc.)

The breast section of these Guidelines and Recommendations for Elastography produced under the auspices of the World Federation of Ultrasound in Medicine and Biology (WFUMB) assesses the clinically used applications of all forms of elastography used in breast imaging. The literature on various breast elastography techniques is reviewed, and recommendations are made on evidence-based results. Practical advice is given on how to perform and interpret breast elastography for optimal results, with emphasis placed on avoiding pitfalls. Artifacts are reviewed, and the clinical utility of some artifacts is discussed. Both strain and shear wave techniques have been shown to be highly accurate in characterizing breast lesions as benign or malignant. The relationship between the various techniques is discussed, and recommended interpretation based on a BI-RADS-like malignancy probability scale is provided. This document is intended to be used as a reference and to guide clinical users in a practical way., (Copyright © 2015. Published by Elsevier Inc.)

Conventional diagnostic ultrasound images of the anatomy (as opposed to blood flow) reveal differences in the acoustic properties of soft tissues (mainly echogenicity but also, to some extent, attenuation), whereas ultrasound-based elasticity images are able to reveal the differences in the elastic properties of soft tissues (e.g., elasticity and viscosity). The benefit of elasticity imaging lies in the fact that many soft tissues can share similar ultrasonic echogenicities but may have different mechanical properties that can be used to clearly visualize normal anatomy and delineate pathologic lesions. Typically, all elasticity measurement and imaging methods introduce a mechanical excitation and monitor the resulting tissue response. Some of the most widely available commercial elasticity imaging methods are 'quasi-static' and use external tissue compression to generate images of the resulting tissue strain (or deformation). In addition, many manufacturers now provide shear wave imaging and measurement methods, which deliver stiffness images based upon the shear wave propagation speed. The goal of this review is to describe the fundamental physics and the associated terminology underlying these technologies. We have included a questions and answers section, an extensive appendix, and a glossary of terms in this manuscript. We have also endeavored to ensure that the terminology and descriptions, although not identical, are broadly compatible across the WFUMB and EFSUMB sets of guidelines on elastography (Bamber et al. 2013; Cosgrove et al. 2013)., (Copyright © 2015. Published by Elsevier Inc.)

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced these guidelines for the use of elastography techniques in liver disease. For each available technique, the reproducibility, results, and limitations are analyzed, and recommendations are given. Finally, recommendations based on the international literature and the findings of the WFUMB expert group are established as answers to common questions. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases., (Copyright © 2015. Published by Elsevier Inc.)

Acoustic radiation force impulse imaging and shear wave elasticity imaging (SWEI) use the dynamic response of tissue to impulsive mechanical stimulus to characterize local elasticity. A variant of conventional, multiple-track-location SWEI, denoted single-track-location SWEI, offers the promise of creating speckle-free shear wave images. This work compares the three imaging modalities using a high push and track beam density combined acquisition sequence to image inclusions of different sizes and contrasts. Single-track-location SWEI is found to have a significantly higher contrast-to-noise ratio than multiple-track-location SWEI, allowing for operation at higher resolution. Acoustic radiation force impulse imaging and single-track-location SWEI perform similarly in the larger inclusions, with single-track-location SWEI providing better visualization of small targets ≤ 2.5 mm in diameter. The processing of each modality introduces different trade-offs between smoothness and resolution of edges and structures; these are discussed in detail., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in the United States and the second leading cause of cancer-related death. Multi-parametric magnetic resonance imaging (mpMRI) has gained recent popularity to characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the potential to aid PCa diagnosis and management by using tissue stiffness to evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging datasets were compared with one another and with gross pathology measurements made immediately after radical prostatectomy. Images were manually segmented in 3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging modalities showed good correlation between estimated organ volume and gross pathologic weights. Ultrasound and MR total prostate volumes were well correlated (R(2) = 0.77), but B-mode images yielded prostate volumes that were larger (16.82% ± 22.45%) than MR images, due to overestimation of the lateral dimension (18.4% ± 13.9%), with less significant differences in the other dimensions (7.4% ± 17.6%, anterior-to-posterior, and -10.8% ± 13.9%, apex-to-base). ARFI and MR CG volumes were also well correlated (R(2) = 0.85). CG volume differences were attributed to ARFI underestimation of the apex-to-base axis (-28.8% ± 9.4%) and ARFI overestimation of the lateral dimension (21.5% ± 14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were well correlated with MR T2-weighted image (T2WI) estimates, with biases in the lateral dimension due to poor contrast caused by extraprostatic fat. B-mode combined with ARFI imaging is a promising low-cost, portable, real-time modality that can complement mpMRI for PCa diagnosis, treatment planning, and management., (© The Author(s) 2014.)

Commercially-available shear wave imaging systems measure group shear wave speed (SWS) and often report stiffness parameters applying purely elastic material models. Soft tissues, however, are viscoelastic, and higher-order material models are necessary to characterize the dispersion associated with broadband shear waves. In this paper, we describe a robust, model-based algorithm and use a linear dispersion model to perform shear wave dispersion analysis in traditionally difficult-to-image subjects. In a cohort of 135 non-alcoholic fatty liver disease patients, we compare the performance of group SWS with dispersion analysis-derived phase velocity c(200 Hz) and dispersion slope dc/df parameters to stage hepatic fibrosis and steatosis. Area under the ROC curve (AUROC) analysis demonstrates correlation between all parameters [group SWS, c(200 Hz), and, to a lesser extent dc/df ] and fibrosis stage, whereas no correlation was observed between steatosis stage and any of the material parameters. Interestingly, optimal AUROC threshold SWS values separating advanced liver fibrosis (≥F3) from mild-to-moderate fibrosis (≤F2) were shown to be frequency-dependent, and to increase from 1.8 to 3.3 m/s over the 0 to 400 Hz shear wave frequency range.

Elastic properties of materials can be measured by observing shear wave propagation following localized, impulsive excitations and relating the propagation velocity to a model of the material. However, characterization of anisotropic materials is difficult because of the number of elasticity constants in the material model and the complex dependence of propagation velocity relative to the excitation axis, material symmetries, and propagation directions. In this study, we develop a model of wave propagation following impulsive excitation in an incompressible, transversely isotropic (TI) material such as muscle. Wave motion is described in terms of three propagation modes identified by their polarization relative to the material symmetry axis and propagation direction. Phase velocities for these propagation modes are expressed in terms of five elasticity constants needed to describe a general TI material, and also in terms of three constants after the application of two constraints that hold in the limit of an incompressible material. Group propagation velocities are derived from the phase velocities to describe the propagation of wave packets away from the excitation region following localized excitation. The theoretical model is compared to the results of finite element (FE) simulations performed using a nearly incompressible material model with the five elasticity constants chosen to preserve the essential properties of the material in the incompressible limit. Propagation velocities calculated from the FE displacement data show complex structure that agrees quantitatively with the theoretical model and demonstrates the possibility of measuring all three elasticity constants needed to characterize an incompressible, TI material., (© 2013 Elsevier Ltd. All rights reserved.)

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo; elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed noninvasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods.

Time-of-flight methods allow quantitative measurement of shear wave speed (SWS) from ultrasonically tracked displacements following impulsive acoustic radiation force excitation in tissue. In heterogeneous materials, reflections at boundaries can distort the wave shape and confound determination of the wave arrival time. The magnitude of these effects depends on the shear wavelength of the excitation, the kernel size used to calculate the SWS, and the method used to determine the wave arrival time. In this study, we perform a parametric analysis of these factors using finite element modeling of the tissue response and simulated ultrasonic tracking. Two geometries are used, a stiff vertical layer and a stiff spherical inclusion, each in a uniform background. Wave arrival times are estimated using the peak displacement, peak slope of the leading edge, and cross-correlation methods. Results are evaluated in terms of reconstruction accuracy, resolution, contrast, and contrast-to-noise ratio of reconstructed SWS images. Superior results are obtained using narrower excitation widths and arrival time estimators which identify the leading edge of the propagating wave. The optimal kernel size is determined by a tradeoff between improved accuracy for larger kernels at the expense of spatial resolution.

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents. In AIM MRI, Mn(2+) acts a calcium analog and accumulates in depolarized neurons. Because Mn(2+) shortens the T1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn(2+) clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn(2+) does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice. One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage. Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response. To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.

The goal of this work is to demonstrate the feasibility of using a diagnostic ultrasound system (Siemens Antares and CH6-2 curvilinear array) to ablate ex vivo liver with a custom M-mode sequence and monitor the resulting tissue stiffening with 2-D Acoustic Radiation Force Impulse (ARFI) imaging. Images were taken before and after ablation, as well as in 5- s intervals during the ablation sequence in order to monitor the ablation lesion formation temporally. Ablation lesions were generated at depths up to 1.5 cm from the surface of the liver and were not visible in B-mode. ARFI images showed liver stiffening with heating that corresponded to discolored regions in gross pathology. As expected, the contrast of ablation lesions in ARFI images is observed to increase with ablation lesion size. This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage and monitor the formation of the ablation lesion with ARFI imaging.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening., Methods: Acoustic Radiation Force Impulse (ARFI) shear wave imaging, a noninvasive method of assessing tissue stiffness, was used to evaluate liver fibrosis in 172 patients diagnosed with NAFLD. Liver shear stiffness measures in three different imaging locations were reconstructed and compared to the histologic features of NAFLD and AST-to-platelet ratio indices (APRI)., Results: Reconstructed shear stiffnesses were not associated with ballooned hepatocytes (p=0.11), inflammation (p=0.69), nor imaging location (p=0.11). Using a predictive shear stiffness threshold of 4.24kPa, shear stiffness distinguished low (fibrosis stage 0-2) from high (fibrosis stage 3-4) fibrosis stages with a sensitivity of 90% and a specificity of 90% (AUC of 0.90). Shear stiffness had a mild correlation with APRI (R(2)=0.22). BMI>40kg/m(2) was not a limiting factor for ARFI imaging, and no correlation was noted between BMI and shear stiffness (R(2)=0.05)., Conclusions: ARFI imaging is a promising imaging modality for assessing the presence or absence of advanced fibrosis in patients with obesity-related liver disease., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)