Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

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.

Shear Wave Imaging of Passive Diastolic Myocardial Stiffness: Stunned Versus Infarcted Myocardium.

OBJECTIVES: The aim of this study was to investigate the potential of shear wave imaging (SWI), a novel ultrasound-based technique, to noninvasively quantify passive diastolic myocardial stiffness in an ovine model of ischemic cardiomyopathy. BACKGROUND: Evaluation of diastolic left ventricular function is critical for evaluation of heart failure and ischemic cardiomyopathy. Myocardial stiffness is known to be an important property for the evaluation of the diastolic myocardial function, but this parameter cannot be measured noninvasively by existing techniques. METHODS: SWI was performed in vivo in open-chest procedures in 10 sheep. Ligation of a diagonal of the left anterior descending coronary artery was performed for 15 min (stunned group, n = 5) and 2 h (infarcted group, n = 5). Each procedure was followed by a 40-min reperfusion period. Diastolic myocardial stiffness was measured at rest, during ischemia, and after reperfusion by using noninvasive shear wave imaging. Simultaneously, end-diastolic left ventricular pressure and segmental strain were measured with a pressure catheter and sonomicrometers during transient vena caval occlusions to obtain gold standard evaluation of myocardial stiffness using end-diastolic strain-stress relationship (EDSSR). RESULTS: In both groups, the end-systolic circumferential strain was drastically reduced during ischemia (from 14.2 ± 1.2% to 1.3 ± 1.6% in the infarcted group and from 13.5 ± 3.0% to 1.9 ± 1.8% in the stunned group; p <0.01). SWI diastolic stiffness increased after 2 h of ischemia from 1.7 ± 0.4 to 6.2 ± 2.2 kPa (p < 0.05) and even more after reperfusion (12.1 ± 4.2 kPa; p < 0.01). Diastolic myocardial stiffening was confirmed by the exponential constant coefficient of the EDSSR, which increased from 8.8 ± 2.3 to 25.7 ± 9.5 (p < 0.01). In contrast, SWI diastolic stiffness was unchanged in the stunned group (2.3 ± 0.4 kPa vs 1.8 ± 0.3 kPa, p = NS) which was confirmed also by the exponential constant of EDSSR (9.7 ± 3.1 vs 10.2 ± 2.3, p = NS). CONCLUSIONS: Noninvasive SWI evaluation of diastolic myocardial stiffness can differentiate between stiff, noncompliant infarcted wall and softer wall containing stunned myocardium.

In Vivo Quantification of the Nonlinear Shear Modulus in Breast Lesions: Feasibility Study.

Breast cancer detection in the early stages is of great importance since the prognosis, and the treatment depends more on this. Multiple techniques relying on the mechanical properties of soft tissues have been developed to help in early detection. In this study, we implemented a technique that measures the nonlinear shear modulus (NLSM) (µ(NL)) in vivo and showed its utility to detect breast lesions from healthy tissue. The technique relies on the acoustoelasticity theory in quasi-incompressible media. In order to recover µ(NL), static elastography and supersonic shear imaging are combined to subsequently register strain maps and shear modulus maps while the medium is compressed. Then, µ(NL) can be recovered from the relationship between the stress, deduced from strain maps, and the shear modulus. For this study, a series of five nonlinear phantoms were built using biological tissue (pork liver) inclusions immersed in an agar-gelatin gel. Furthermore, 11 in vivo acquisitions were performed to characterize the NLSM of breast tissue. The phantom results showed a very good differentiation of the liver inclusions when measuring µ(NL) with a mean value of -114.1 kPa compared to -34.7 kPa for the gelatin. Meanwhile, values for the shear modulus for the liver and the gelatin were very similar, 3.7 and 3.4 kPa, respectively. In vivo NLSM mean value for the healthy breast tissue was of -95 kPa, while mean values of the benign and the malignant lesions were -619 and -806 kPa with a strong v ariability, respectively. This study shows the potential of the acoustoelasticity theory in quasi-incompressible medium to bring a new parameter for breast cancer diagnosis.

Carotid stiffness change over the cardiac cycle by ultrafast ultrasound imaging in healthy volunteers and vascular Ehlers-Danlos syndrome.

OBJECTIVES: Arterial stiffness is related to age and collagen properties of the arterial wall and can be indirectly evaluated by the pulse wave velocity (PWV). Ultrafast ultrasound imaging, a unique ultrahigh frame rate technique (>10, 000 images/s), recently emerged enabling direct measurement of carotid PWV and its variation over the cardiac cycle. Our goal was to characterize the carotid diastolic-systolic arterial stiffening using ultrafast ultrasound imaging in healthy individuals and in vascular Ehlers-Danlos syndrome (vEDS), in which collagen type III is defectuous. METHODS: Ultrafast ultrasound imaging was performed on common carotids of 102 healthy individuals and 37 consecutive patients with vEDS. Results are mean ±â€Šstandard deviation. RESULTS: Carotid ultrafast ultrasound imaging PWV in healthy individuals was 5.6 ±â€Š1.2 in early systole and 7.3 ±â€Š2.0  m/s in end systole, and correlated with age (r = 0.48; P < 0.0001 and r = 0.68; P < 0.0001, respectively). Difference between early and end-systole PWV increased with age independently of blood pressure (r = 0.54; P < 0.0001). In patients with vEDS, ultrafast ultrasound imaging PWV was 6.0 ±â€Š1.5 in early systole and 6.7 ±â€Š1.5  m/s in end systole. Carotid stiffness change over the cardiac cycle was lower than in healthy people (0.021 vs. 0.057  m/s per mmHg; P = 0.0035). CONCLUSION: Ultrafast ultrasound imaging can evaluate carotid PWV and its variation over the cardiac cycle. This allowed to demonstrate the age-induced increase of the arterial diastolic-systolic stiffening in healthy people and a lower stiffening in vEDS, both characterized by arterial complications. We believe that this easy-to-use technique could offer the opportunity to go beyond the diastolic PWV to better characterize arterial stiffness change with age or other collagen alterations.

Muscle shear elastic modulus is linearly related to muscle torque over the entire range of isometric contraction intensity.

Muscle shear elastic modulus is linearly related to muscle torque during low-level contractions (<60% of Maximal Voluntary Contraction, MVC). This measurement can therefore be used to estimate changes in individual muscle force. However, it is not known if this relationship remains valid for higher intensities. The aim of this study was to determine: (i) the relationship between muscle shear elastic modulus and muscle torque over the entire range of isometric contraction and (ii) the influence of the size of the region of interest (ROI) used to average the shear modulus value. Ten healthy males performed two incremental isometric little finger abductions. The joint torque produced by Abductor Digiti Minimi was considered as an index of muscle torque and elastic modulus. A high coefficient of determination (R(2)) (range: 0.86-0.98) indicated that the relationship between elastic modulus and torque can be accurately modeled by a linear regression over the entire range (0% to 100% of MVC). The changes in shear elastic modulus as a function of torque were highly repeatable. Lower R(2) values (0.89±0.13 for 1/16 of ROI) and significantly increased absolute errors were observed when the shear elastic modulus was averaged over smaller ROI, half, 1/4 and 1/16 of the full ROI) than the full ROI (mean size: 1.18±0.24cm(2)). It suggests that the ROI should be as large as possible for accurate measurement of muscle shear modulus.

High-contrast ultrafast imaging of the heart.

Noninvasive ultrafast imaging of intrinsic waves such as electromechanical waves or remotely induced shear waves in elastography imaging techniques for human cardiac applications remains challenging. In this paper, we propose ultrafast imaging of the heart with adapted sector size by coherently compounding diverging waves emitted from a standard transthoracic cardiac phased-array probe. As in ultrafast imaging with plane wave coherent compounding, diverging waves can be summed coherently to obtain high-quality images of the entire heart at high frame rate in a full field of view. To image the propagation of shear waves with a large SNR, the field of view can be adapted by changing the angular aperture of the transmitted wave. Backscattered echoes from successive circular wave acquisitions are coherently summed at every location in the image to improve the image quality while maintaining very high frame rates. The transmitted diverging waves, angular apertures, and subaperture sizes were tested in simulation, and ultrafast coherent compounding was implemented in a commercial scanner. The improvement of the imaging quality was quantified in phantoms and in one human heart, in vivo. Imaging shear wave propagation at 2500 frames/s using 5 diverging waves provided a large increase of the SNR of the tissue velocity estimates while maintaining a high frame rate. Finally, ultrafast imaging with 1 to 5 diverging waves was used to image the human heart at a frame rate of 4500 to 900 frames/s over an entire cardiac cycle. Spatial coherent compounding provided a strong improvement of the imaging quality, even with a small number of transmitted diverging waves and a high frame rate, which allows imaging of the propagation of electromechanical and shear waves with good image quality.

Mapping myocardial fiber orientation using echocardiography-based shear wave imaging.

The assessment of disrupted myocardial fiber arrangement may help to understand and diagnose hypertrophic or ischemic cardiomyopathy. We hereby proposed and developed shear wave imaging (SWI), which is an echocardiography-based, noninvasive, real-time, and easy-to-use technique, to map myofiber orientation. Five in vitro porcine and three in vivo open-chest ovine hearts were studied. Known in physics, shear wave propagates faster along than across the fiber direction. SWI is a technique that can generate shear waves travelling in different directions with respect to each myocardial layer. SWI further analyzed the shear wave velocity across the entire left-ventricular (LV) myocardial thickness, ranging between 10 (diastole) and 25 mm (systole), with a resolution of 0.2 mm in the middle segment of the LV anterior wall region. The fiber angle at each myocardial layer was thus estimated by finding the maximum shear wave speed. In the in vitro porcine myocardium (n=5) , the SWI-estimated fiber angles gradually changed from +80° ± 7° (endocardium) to +30° ± 13° (midwall) and -40° ± 10° (epicardium) with 0° aligning with the circumference of the heart. This transmural fiber orientation was well correlated with histology findings. SWI further succeeded in mapping the transmural fiber orientation in three beating ovine hearts in vivo. At midsystole, the average fiber orientation exhibited 71° ± 13° (endocardium), 27° ± 8° (midwall), and -26° ± 30° (epicardium). We demonstrated the capability of SWI in mapping myocardial fiber orientation in vitro and in vivo. SWI may serve as a new tool for the noninvasive characterization of myocardial fiber structure.

Assessment of viscous and elastic properties of sub-wavelength layered soft tissues using shear wave spectroscopy: theoretical framework and in vitro experimental validation.

In elastography, quantitative imaging of soft tissue elastic properties is provided by local shear wave speed estimation. Shear wave imaging in a homogeneous medium thicker than the shear wavelength is eased by a simple relationship between shear wave speed and local shear modulus. In thin layered organs, the shear wave is guided and thus undergoes dispersive effects. This case is encountered in medical applications such as elastography of skin layers, corneas, or arterial walls. In this work, we proposed and validated shear wave spectroscopy as a method for elastic modulus quantification in such layered tissues. Shear wave dispersion curves in thin layers were obtained by finite-difference simulations and numerical solving of the boundary conditions. In addition, an analytical approximation of the dispersion equation was derived from the leaky Lamb wave theory. In vitro dispersion curves obtained from phantoms were consistent with numerical studies (deviation <1.4%). The least-mean-squares fitting of the dispersion curves enables a quantitative and accurate (error < 5% of the transverse speed) assessment of the elasticity. Dispersion curves were also found to be poorly influenced by shear viscosity. This phenomenon allows independent recovery of the shear modulus and the viscosity, using, respectively, the dispersion curve and the attenuation estimation along the propagation axis.

Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients.

Supersonic shear imaging (SSI) has recently been demonstrated to be a repeatable and reproducible transient bidimensional elastography technique. We report a prospective clinical evaluation of the performances of SSI for liver fibrosis evaluation in 113 patients with hepatitis C virus (HCV) and a comparison with FibroScan (FS). Liver elasticity values using SSI and FS ranged from 4.50 kPa to 33.96 kPa and from 2.60 kPa to 46.50 kPa, respectively. Analysis of variance (ANOVA) shows a good agreement between fibrosis staging and elasticity assessment using SSI and FS (p < 10(-5)). The areas under receiver operating characteristic (ROC) curves for elasticity values assessed from SSI were 0.948, 0.962 and 0.968 for patients with predicted fibrosis levels F ≥ 2, F ≥ 3 and F = 4, respectively. These values are compared with FS area under the receiver operating characteristic curve (AUROC) of 0.846, 0.857 and 0.940, respectively. This comparison between ROC curves is particularly significant for mild and intermediate fibrosis levels. SSI appears to be a fast, simple and reliable method for noninvasive liver fibrosis evaluation.

Real-time assessment of myocardial contractility using shear wave imaging.

OBJECTIVES: The goal of this study was to assess whether myocardial stiffness could be measured by shear wave imaging (SWI) and whether myocardial stiffness accurately quantified myocardial function. BACKGROUND: SWI is a novel ultrasound-based technique for quantitative, local, and noninvasive mapping of soft tissue elastic properties. METHODS: SWI was performed in Langendorff perfused isolated rat hearts (n = 6). Shear wave was generated and imaged in the left ventricular myocardium using a conventional ultrasonic probe connected to an ultrafast scanner (12,000 frames/s). The local myocardial stiffness was derived from shear wave velocity every 7.5 ms during 1 single cardiac cycle. RESULTS: The average myocardial stiffness was 8.6 ± 0.7 kPa in systole and 1.7 ± 0.8 kPa in diastole. Myocardial stiffness was compared with isovolumic systolic pressure at rest and during administration of isoproterenol (10(-9), 10(-8), and 10(-7) mol/l, 5 min each). Systolic myocardial stiffness increased strongly up to 23.4 ± 3.4 kPa. Myocardial stiffness correlated strongly with isovolumic systolic pressure (r(2) = [0.94; 0.98], p < 0.0001). CONCLUSIONS: Myocardial stiffness can be measured in real time over the cardiac cycle using SWI, which allows quantification of stiffness variation between systole and diastole. Systolic myocardial stiffness provides a noninvasive index of myocardial contractility.

In vivo quantitative mapping of myocardial stiffening and transmural anisotropy during the cardiac cycle.

Shear wave imaging was evaluated for the in vivo assessment of myocardial biomechanical properties on ten open chest sheep. The use of dedicated ultrasonic sequences implemented on a very high frame rate ultrasonic scanner ( > 5000 frames per second) enables the estimation of the quantitative shear modulus of myocardium several times during one cardiac cycle. A 128 element probe remotely generates a shear wave thanks to the radiation force induced by a focused ultrasonic burst. The resulting shear wave propagation is tracked using the same probe by cross-correlating successive ultrasonic images acquired at a very high frame rate. The shear wave speed estimated at each location in the ultrasonic image gives access to the local myocardial stiffness (shear modulus µ). The technique was found to be reproducible (standard deviation ) and able to estimate both systolic and diastolic stiffness on each sheep (respectively µ(dias) ≈ 2 kPa and µ(syst) ≈ 30 kPa). Moreover, the ability of the proposed method to polarize the shear wave generation and propagation along a chosen axis permits the study the local elastic anisotropy of myocardial muscle. As expected, myocardial elastic anisotropy is found to vary with muscle depth. The real time capabilities and potential of Shear Wave Imaging using ultrafast scanners for cardiac applications is finally illustrated by studying the dynamics of this fractional anisotropy during the cardiac cycle.

Quantitative assessment of arterial wall biomechanical properties using shear wave imaging.

A new ultrasound-based technique is proposed to assess the arterial stiffness: the radiation force of an ultrasonic beam focused on the arterial wall induces a transient shear wave (∼10 ms) whose propagation is tracked by ultrafast imaging. The large and high-frequency content (100 to 1500 Hz) of the induced wave enables studying the wave dispersion, which is shown experimentally in vitro and numerically to be linked to arterial wall stiffness and geometry. The proposed method is applied in vivo. By repeating the acquisition up to 10 times per second (theoretical maximal frame rate is ∼100 Hz), it is possible to assess in vivo the arterial wall elasticity dynamics: shear modulus of a healthy volunteer carotid wall is shown to vary strongly during the cardiac cycle and measured to be 130 ± 15 kPa in systole and 80 ± 10 kPa in diastole.