Search

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.)

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.)

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.)

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].

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.)

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.)

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.)

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.)

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.

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.

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.)

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.)

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.

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.)

A noninvasive method of characterizing myocardial stiffness could have significant implications in diagnosing cardiac disease. Acoustic radiation force (ARF)-driven techniques have demonstrated their ability to discern elastic properties of soft tissue. For the purpose of myocardial elasticity imaging, a novel ARF-based imaging technique, the displacement ratio rate (DRR) method, was developed to rank the relative stiffnesses of dynamically varying tissue. The basis and performance of this technique was demonstrated through numerical and phantom imaging results. This new method requires a relatively small temporal (<1 ms) and spatial (tenths of mm(2)) sampling window and appears to be independent of applied ARF magnitude. The DRR method was implemented in two in vivo canine studies, during which data were acquired through the full cardiac cycle by imaging directly on the exposed epicardium. These data were then compared with results obtained by acoustic radiation force impulse (ARFI) imaging and shear wave velocimetry, with the latter being used as the gold standard. Through the cardiac cycle, velocimetry results portray a range of shear wave velocities from 0.76-1.97 m/s, with the highest velocities observed during systole and the lowest observed during diastole. If a basic shear wave elasticity model is assumed, such a velocity result would suggest a period of increased stiffness during systole (when compared with diastole). Despite drawbacks of the DRR method (i.e., sensitivity to noise and limited stiffness range), its results predicted a similar cyclic stiffness variation to that offered by velocimetry while being insensitive to variations in applied radiation force., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Elasticity-based imaging modalities are becoming popular diagnostic tools in clinical practice. Gelatin-based, tissue mimicking phantoms that contain graphite as the acoustic scattering material are commonly used in testing and validating elasticity-imaging methods to quantify tissue stiffness. The gelatin bloom strength and concentration are used to control phantom stiffness. While it is known that graphite concentration can be modulated to control acoustic attenuation, the impact of graphite concentration on phantom elasticity has not been characterized in these gelatin phantoms. This work investigates the impact of graphite concentration on phantom shear stiffness as characterized by shear-wave speed measurements using impulsive acoustic-radiation-force excitations. Phantom shear-wave speed increased by 0.83 (m/s)/(dB/(cm MHz)) when increasing the attenuation coefficient slope of the phantom material through increasing graphite concentration. Therefore, gelatin-phantom stiffness can be affected by the conventional ways that attenuation is modulated through graphite concentration in these phantoms.

Time-of-flight methods allow quantitative measurement of shear wave speed (SWS) from ultrasonically tracked displacements following impulsive excitation in tissue. However, application of these methods to in vivo data are challenging because of the presence of gross outlier data resulting from sources such as physiological motion or spatial inhomogeneities. This paper describes a new method for estimating SWS by considering a solution space of trajectories and evaluating each trajectory using a metric that characterizes wave motion along the entire trajectory. The metric used here is found by summing displacement data along the trajectory as in the calculation of projection data in the Radon transformation. The algorithm is evaluated using data acquired in calibrated phantoms and in vivo human liver. Results are compared with SWS estimates using a random sample consensus (RANSAC) algorithm described by Wang et al. Good agreement is found between the Radon sum and RANSAC SWS estimates with a correlation coefficient of greater than 0.99 for phantom data and 0.91 for in vivo liver data. The Radon sum transformation is suitable for use in situations requiring real-time feedback and is comparably robust to the RANSAC algorithm with respect to outlier data.

The stiffness of tissue can be quantified by measuring the shear wave speed (SWS) within the medium. Ultrasound is a real-time imaging modality capable of tracking the propagation of shear waves in soft tissue. Time-of-flight (TOF) methods have previously been shown to be effective for quantifying SWS from ultrasonically tracked displacements. However, the application of these methods to in vivo data is challenging due to the presence of additional sources of error, such as physiologic motion or spatial inhomogeneities in tissue. This article introduces the use of random sample consensus (RANSAC), a model fitting paradigm robust to the presence of gross outlier data, for estimating the SWS from ultrasonically tracked tissue displacements in vivo. SWS reconstruction is posed as a parameter estimation problem and the RANSAC solution to this problem is described. Simulations using synthetic TOF data show that RANSAC is capable of good stiffness reconstruction accuracy (mean error 0.5 kPa) and precision (standard deviation 0.6 kPa) over a range of shear stiffness (0.6-10 kPa) and proportion of inlier data (50%-95%). As with all TOF SWS estimation methods, the accuracy and precision of the RANSAC reconstructed shear modulus decreases with increasing tissue stiffness. The RANSAC SWS estimator was applied to radiation force induced shear wave data from 123 human patient livers acquired with a modified SONOLINE Antares ultrasound system (Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA) in a clinical setting before liver biopsy was performed. Stiffness measurements were not possible in 19 patients due to the absence of shear wave propagation inside the liver. The mean liver stiffness for the remaining 104 patients ranged from 1.3 to 24.2 kPa and the proportion of inliers for the successful reconstructions ranged between 42% to 99%. Using RANSAC for SWS estimation improved the diagnostic accuracy of liver stiffness for delineating fibrosis stage compared with ordinary least squares (OLS) without outlier removal (AUROC = 0.94 for F >or= 3 and AUROC = 0.98 for F = 4). These results show that RANSAC is a suitable method for estimating the SWS from noisy in vivo shear wave displacements tracked by ultrasound., (Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Novel methods need to be developed to detect electrical instability in children. The dynamical properties of action potential restitution play an important role in the development of instability leading to arrhythmias. A new method, the Restitution Portrait (RP), was developed to visualize and quantify these properties at the action potential level. Here, we apply the RP method using the activation-recovery interval (ARI) from the ECG to detect, in vitro, repolarization abnormalities in neonatal and preadolescent rabbit myocardium with drug-induced Long QT Syndrome (LQTS Type 1 or Type 2). The ECG was recorded during programmed endocardial pacing to record the RP. The ECG RP demonstrated significant changes in dynamical restitution components during drug-induced LQTS compared to baseline. This study shows that the ECG RP may be an important noninvasive diagnostic tool for detecting electrical instability in the young.

We quantitatively compare filtered backprojection (FBP), expectation-maximization (EM), and Bayesian reconstruction algorithms as applied to the IndyPET scanner--a dedicated research scanner which has been developed for small and intermediate field of view imaging applications. In contrast to previous approaches that rely on Monte Carlo simulations, a key feature of our investigation is the use of an empirical system kernel determined from scans of line source phantoms. This kernel is incorporated into the forward model of the EM and Bayesian algorithms to achieve resolution recovery. Three data sets are used, data collected on the IndyPET scanner using a bar phantom and a Hoffman three-dimensional brain phantom, and simulated data containing a hot lesion added to a uniform background. Reconstruction quality is analyzed quantitatively in terms of bias-variance measures (bar phantom) and mean square error (lesion phantom). We observe that without use of the empirical system kernel, the FBP, EM, and Bayesian algorithms give similar performance. However, with the inclusion of the empirical kernel, the iterative algorithms provide superior reconstructions compared with FBP, both in terms of visual quality and quantitative measures. Furthermore, Bayesian methods outperform EM. We conclude that significant improvements in reconstruction quality can be realized by combining accurate models of the system response with Bayesian reconstruction algorithms.

Optical methods were used to study the Ca2+ dependence of vesicle cycling in bipolar cells isolated from goldfish retinas. Uniformly raising the Ca2+ concentration to between 0.8 and 20 microM produced a continuous vesicle cycle of balanced exocytosis and endocytosis with a maximum rate equivalent to the turnover of the entire surface membrane of a terminal every 2 min (or approximately 900 vesicles sec-1). Increasing the Ca2+ concentration above 20 microM inhibited continuous vesicle cycling. In contrast, influx of Ca2+ through voltage-gated channels produced a transient burst of exocytosis that increased the surface area of a terminal by a maximum of 12% (equivalent to the addition of 13,000 vesicles). Endocytosis was delayed until after Ca2+ influx stopped and the average Ca2+ concentration in the terminal declined. Hence, a single terminal has mechanisms for both continuous and transient vesicle cycling.