Assessment of the uncertainty of shear wave speed measurements in ultrasound elastography.

We have fabricated a cylindrical intravascular ultrasound (IVUS) transducer array prototype capable of generating an acoustic radiation force impulse (ARFI) for shear wave elasticity imaging (SWEI). The prototype array was a 4-mm long, 2.5-mm diameter, 4 MHz PZT-8 tube, axially segmented into 12 elements on a 334 µm pitch. This transducer array was used in custom vessel phantoms and in ex vivo porcine artery experiments to investigate the potential for IVUS SWEI to distinguish soft lipid cores from stiffer surrounding tissues. By using this array transducer to generate a radially-directed ARFI “push”, and a Verasonics linear array probe to track displacements in planes parallel to the “push”, SWEI images of a vessel phantom with hard vessel walls and a soft inclusion were obtained. In tissue-mimicking phantoms, focusing the transducer array to a range of 5 mm generated ARFI displacements up to 1.36 and 1.76 times greater than unfocused excitations in the soft and stiff regions, respectively. The measured shear wave speed in the soft inclusion and stiff vessel wall was 0.97±0.59 m/s and 1.66±0.91 m/s, respectively, and was close to the calibrated measurements of 1.21±0.05 m/s and 1.56±0.05 m/s, respectively. A SWEI image of an ex vivo porcine renal artery was obtained using the prototype transducer and external tracking array, and showed an average shear wave speed of 3.97±1.12 m/s. These results demonstrate the potential of this IVUS array to enable SWEI, to quantifiably assess vulnerable vascular plaques.

To assess the performance of conventional high frequency ultrasound (US) and US elastography in diagnosis of complex cystic and solid breast lesions. Ninety three lesions in 93 patients underwent conventional US and US elastography, including strain elastography, acoustic radiation force impulse (ARFI) imaging, and point shear wave speed (SWS) measurement. Pathological examination revealed 31 (33.3%) of the 93 lesions were malignant and the remaining 62 (66.7%) were benign. Multivariate analysis showed that elder patient (OR: 25.301), internal vascularity (OR: 4.518), and not circumscribed margin (OR: 3.813) were independent predictors for malignancy, while predominately cystic lesions (OR: 0.178) was a predictor for benign lesions (all p < 0.05). Invalid SWS measurement was occurred in 19 of 31 (61.3%) malignant lesions and 16 of 62 (25.8%) benign lesions, respectively (p < 0.05). The mean SWS value for malignant lesions was significantly lower than that for benign ones, being 1.60±0.63 m/s (range, 0.68-2.70 m/s) versus 2.33±0.77 m/s (range, 0.67-3.97 m/s) (p < 0.05). Areas under the ROC curve (Azs) for Breast Imaging Reporting and Data System (BI-RADS) assessment, strain elasticity score, ARFI imaging and valid point SWS measurement were 0.844, 0.734, 0.763 and 0.778,respectively. US BI-RADS category, strain elastography score, ARFI imaging patterns and point SWS measurement are useful for malignancy prediction of complex cystic and solid breast lesions. The result that SWS for malignant lesions is lower than benign one should be carefully interpreted since invalid SWS measurement is excluded for analysis. The true stiffness of malignant cystic and solid lesions should be further evaluated with a new generation of two-dimensional SWS imaging.

Sclerotic skin diseases are associated with inflammation and fibrosis in the dermis, and these changes in collagen content with disease progression make this pathology amenable to being characterized with Acoustic Radiation Force Impulse (ARFI) and Shear Wave Elasticity Imaging (SWEI) methods. We characterized skin stiffness in healthy individuals at repeated three month intervals and compared sclerotic to healthy skin stiffness. ARFI and SWEI were implemented using a Siemens 14L5 linear array on an ACUSON S2000™ scanner. A single dermatologist performed all imaging in twenty-two patients. Normal and sclerotic skin stiffnesses were characterized by (1) mean ARFI displacement magnitude, and (2) group shear wave speed estimated using a Radon sum of shear wave velocity data. Imaging was performed at different anatomic sites, including the upper and lower back, arm, forearm, abdomen, thigh and calf. Five repeat data acquisitions were performed in each anatomic location. ARFI displacement and SWEI shear wave speeds were reconstructed in 96% of all acquisitions when the region of interest was exclusively contained in the dermis. Overall, ARFI and SWEI metrics showed no significant difference between contralateral imaging locations across different anatomic sites in healthy skin (p 200% greater in sclerotic lesions than in contralateral healthy skin in patients with graft-versus-host disease (GVHD) (p < 0.01), and 25% greater in patients with morphea. ARFI displacements exhibited greater variability than shear wave speed in characterizing sclerotic skin, showing a 61% decrease compared to healthy skin in GVHD patients (p < 0.05) and a 19% decrease in morphea patients (p < 0.05). ARFI and SWEI are able differentiate sclerotic skin lesions from healthy skin, and studies are underway to evaluate their utility in longitudinally-monitoring disease progression and response to therapy. Additional study details, data and conclusions can be found in the full-length manuscript describing this work [1].

The acoustic radiation force impulse (ARFI) has been widely used in transient shear wave elasticity imaging (SWEI). For SWEI based on focused ARFI, the highest image quality exists inside the focal zone due to the limitation of the depth of focus and diffraction. Consequently, the areas outside the focal zone and in the near field present poor image quality. To address the limitations of the focused beam, we introduce Bessel apodized ARFI that enhances image quality and improves the depth of focus. The objective of this study is to evaluate the feasibility of SWEI based on Bessel ARF in simulation and experiment. We report measurements of elastogram image quality and depth of field in tissue-mimicking phantoms and ex vivo liver tissue. Our results demonstrate improved depth of field, image quality, and shear wave speed (SWS) estimation accuracy using Bessel push beams. As a result, Bessel ARF enlarges the field of view of elastograms. The signal-to-noise ratio (SNR) of Bessel SWEI is improved 26% compared with focused SWEI in homogeneous phantom. The estimated SWS by Bessel SWEI is closer to the measured SWS from a clinical scanner with an error of 0.3% compared to 2.4% with a focused beam. In heterogeneous phantoms, the contrast-to-noise ratios (CNRs) of shallow and deep inclusions are improved by 8.79 and 3.33 dB, respectively, under Bessel ARF. We also compare the results between Bessel SWEI and supersonic shear imaging (SSI), and the SNR of Bessel SWEI is improved by 8.1%. Compared with SSI, Bessel SWEI shows more accurate SWS estimates in high stiffness inclusions. Finally, Bessel SWEI can generate higher quality elastograms with less energy than conventional SSI.

A pilot study of ultrasound elastography as a non-invasive method to monitor liver disease in children with short bowel syndrome

This work discusses eight sources of uncertainty and bias arising from system dependent parameters in ultrasound shear wave speed (SWS) measurement. Each of the eight error sources of error we have identified is discussed in the context of a linear, isotropic, elastic, homogeneous medium, combining previously reported analyses with Field II simulations, full-wave 2D 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, master clock jitter, and phase aberration cause uncertainties (variance) in SWS measurements, while pulse repetition frequency and beamforming errors, as well as coupling medium sound speed mismatch cause biases in SWS measurements (accuracy errors). Calibration of these sources of error is an important step in the development of shear wave imaging systems. In a well-calibrated system, where the sources of biases are minimized, and averaging over an ROI is employed to reduce the sources of uncertainty, a SWS error < 3% can be expected.

Shear Wave Elasticity Imaging (SWEI) is commonly used to characterize tissue elasticity, but conventional, multiple-track-location SWEI (MTL-SWEI) techniques are resolution-limited by speckle. MTL-SWEI techniques use plane wave ultrasound to monitor an induced shear wave as it propagates across a set of tracking beams within a region of interest. The scattering process creates a random, yet stationary, spatial sensitivity pattern for each beamformed location, called speckle bias, which causes errors in MTL-SWEI shear wave speed estimates that cannot be improved through averaging. Single Track Location SWEI (STL-SWEI) overcomes speckle bias by using a single track beam, subsequently exciting and tracking different push locations, and comparing the timing of the recorded shear wave signals from different push locations to estimate shear wave speed. Two and three-dimensional STL-SWEI imaging techniques are presented and compared to MTL-SWEI and Acoustic Radiation Force Impulse (ARFI) imaging in phantoms and in vivo experiments. Tradeoffs and techniques for sequencing, beamforming, shear wave speed estimation, and image formation are discussed. For applications where tissue heating and motion are not limiting factors, STL-SWEI provides superior imaging in terms of lateral resolution and contrast-to-noise ratio compared to MTL-SWEI and ARFI. [This work was supported by NIHR37HL096023 and NIHR01EB01248.]

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.

Shear wave speed measurements are used in elasticity imaging to find the shear elasticity and viscosity of tissue. A technique called shear wave dispersion ultrasound vibrometry (SDUV) has been introduced to use the dispersive nature of shear wave speed to locally estimate the material properties of tissue. Shear waves are created using a multifrequency ultrasound radiation force, and the propagating shear waves are measured a few millimeters away from the excitation point. The shear wave speed is measured using a repetitive pulse-echo method and Kalman filtering to find the phase of the harmonic shear wave at two different locations. Using the following relationship, c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> = omega <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> Deltar/Deltaphi where omega <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> is the shear wave frequency, Deltar is the distance between measurement points, Deltaphi is the phase difference, the shear wave speed, c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> , can be estimated. A viscoelastic Voigt model and the shear wave speed measurements at different frequencies are used to find the shear elasticity (mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> ) and viscosity (mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) of the tissue. The purpose of this paper is to assess the accuracy of the SDUV method over a range of different values of mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> and mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . A motion detection model of a vibrating scattering medium was used to analyze measurement errors of vibration phase in a scattering medium. To assess the accuracy of the SDUV method, we modeled the propagation of phase errors into errors in the shear wave speed and material property estimates while varying parameters such as shear stiffness and viscosity, shear wave amplitude, Deltar, signal-to-noise ratio (SNR) of the ultrasound pulse-echo method, and the frequency range of the measurements. We performed an experiment in a section of porcine muscle to evaluate variation of the aforementioned parameters on the shear wave speed and material property measurements and to validate the computer model. The model showed that errors in the shear wave speed and material property estimates were minimized by maximizing shear wave amplitude, pulse-echo SNR, Deltar, and the frequency range used. The experimental model showed optimum performance could be obtained for Deltar = 3-6 mm, SNR ges 20 dB, with a frequency range is 100-600 Hz, and with a shear wave amplitude on the order of a few microns down to 0.5 mum. We present a computational model and experimental approach to analyze errors in measurements of shear wave speed and material properties. The model provides a basis to explore different parameters related to implementation of the SDUV method. The experiment confirmed conclusions made by the model, and the results can be used for optimization of SDUV.

Ultrasound Elastography to Quantify Liver Disease Severity in Autosomal Recessive Polycystic Kidney Disease

Detection of Changes in Cervical Softness Using Shear Wave Speed in Early versus Late Pregnancy: An in Vivo Cross-Sectional Study

Little published research has shown the relationship between noninvasive US shear wave speed (SWS) measurements and degree of liver fibrosis as established by percutaneous biopsy in children. To assess the relationship between liver US shear wave speed (SWS) measurements and parenchymal fibrosis in children. Sixty-two children (0-18 years old) with known or suspected liver disease underwent same-day US shear wave elastography (SWE) and clinically ordered percutaneous core needle biopsy. SWE was performed just before the liver biopsy in the area targeted for sampling, using an Acuson S3000 US system with a 9L4 transducer; six SWS measurements were acquired using Virtual Touch Quantification (VTQ) and Virtual Touch IQ (VTIQ) modes. Biopsy specimens were scored for histological fibrosis and inflammation. Bivariate relationships were assessed using Pearson correlation, while multiple linear regression analysis was used to establish the relationship between SWS and predictor variables. Receiver operating characteristic (ROC) curves were created to assess the abilities of VTQ and VTIQ to discern low vs. high liver fibrosis (histological fibrosis scores 0-2 vs. 3-6). There were significant positive correlations between liver histological fibrosis score and VTQ (n = 49) and VTIQ (n = 48) mean shear wave speed measurements (r = 0.68 and r = 0.73; P-values <0.0001). There also were significant positive correlations between liver histological inflammation score and VTQ and VTIQ mean shear wave speed measurements (r = 0.47 and r = 0.44, and P = 0.0006 and P = 0.0016, respectively). For VTQ, both histological fibrosis (P < 0.0001) and inflammation (P = 0.04) scores were significant predictors of shear wave speed (model adjusted R (2) = 0.49). For VTIQ, only histological fibrosis score (P < 0.0001) was a significant predictor of shear wave speed (model adjusted R (2) = 0.56). ROC areas under the curve were 0.84 and 0.86 for VTQ and VTIQ, respectively. Liver US shear wave speed measurements increase with increasing parenchymal fibrosis in children.

The purpose of the study was to explore the differences of conventional ultrasound characteristics, thyroid imaging reporting and data system (TI-RADS) category and shear wave speed (SWS) measurement between follicular adenoma (FA) and follicular thyroid carcinoma (FTC). Twenty-eight FTCs and 67 FAs proven by surgery were retrospectively included for analysis. Conventional ultrasound and point-shear wave elastography (p-SWE) were performed in all of the included patients. The ultrasound features, American Thyroid Association (ATA) TI-RADS category and American College of Radiology (ACR) TI-RADS category, SWS measurement were compared between the two groups. Receiver operating characteristic (ROC) curve was performed and area under ROC curve (AUC) was obtained for significant features. There were no statistical differences in mean age (46.9±15.7years vs. 48.6±13.6years, P = 0.639), gender (9 males, 32.1% vs. 18 males, 29.0%, P = 0.766) and mean diameter (28.3±16.2 mm vs. 33.8±11.9 mm, P = 0.077) between FTCs and FAs. Hypoechogenicity, lobulated or irregular margin, macrocalcification were more common in FTCs than FAs (all P < 0.05). Mean SWS of FTCs (2.29±0.64 m/s) was slightly higher than that of FAs (1.94±0.68 m/s) (P = 0.023). The AUCs were 0.655, 0.744, and 0.744 with the cut-off SWS≥1.89 m/s, ACR TI-RADS category 4 and intermediate suspicion of ATA TI-RADS category. The sensitivity and AUC were 82.1% and 0.812 with combined ultrasound features of hypoechogenicity, lobulated or irregular margin and macrocalcification. In Conclusion, SWS measurement and TI-RADS categories were useful for the identification of FTCs from FAs.

ARFI and shear wave imaging of the prostate to delineate clinically-significant cancers

Purpose To evaluate the correlation between ultrasonographic (US) point shear-wave elastography (SWE) and magnetic resonance (MR) elastography liver shear-wave speed (SWS) measurements in a pediatric population and to determine if US data dispersion affects this relationship. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant investigation; informed consent and patient assent (as indicated) were obtained. Patients (age range, 0-21 years) undergoing clinical liver MR elastography between July 2014 and November 2015 were prospectively enrolled. Patients underwent two-dimensional gradient-recalled-echo 1.5-T MR elastography with point SWE performed immediately before or immediately after MR elastography. Spearman rank correlation coefficients were calculated to assess the relationship and agreement between point SWE and MR elastography SWS measurements. Uni- and multivariate logistic regression were performed to identify predictors of US data dispersion, with the best multivariate model selected based on Akaike information criterion. Results A total of 55 patients (24 female) were enrolled (mean age, 14.0 years ± 3.9 (standard deviation) (range, 3.5-21.4 years). There was fair correlation between point SWE and MR elastography SWS values for all patients (ρ = 0.33, P = .016). Correlation was substantial, however, when including only patients with minimal US data dispersion (n = 26, ρ = 0.61, P = .001). Mean body mass index (BMI) was significantly lower in patients with minimal US data dispersion than in those with substantial US data dispersion (25.4 kg/m2 ± 7.8 vs 32.3 kg/m2 ± 8.3, P = .003). At univariate analysis, BMI (odds ratio, 1.12; 95% confidence interval [CI]: 1.03, 1.21; P = .006) and abdominal wall thickness (odds ratio, 2.50; 95% CI: 1.32, 4.74; P = .005) were significant predictors of US data dispersion. In the best multivariate model, BMI was the only significant predictor (odds ratio, 1.11; 95% CI: 1.03, 1.20; P = .009). Conclusion Point SWE and MR elastography liver SWS measurements correlate well in patients with a BMI of less than 30 kg/m2 and minimal US data dispersion; increasing US data dispersion is directly related to a higher BMI. © RSNA, 2016.