Viscoelastic and Anisotropic Mechanical Properties of in vivo Muscle Tissue Assessed by Supersonic Shear Imaging

The in vivo assessment of the biomechanical properties of the skeletal muscle is a complex issue because the muscle is an anisotropic, viscoelastic and dynamic medium. In this article, these mechanical properties are characterized for the brachialis muscle in vivo using a noninvasive ultrasound-based technique. This supersonic shear imaging technique combines an ultra-fast ultrasonic system and the remote generation of transient mechanical forces into tissue via the radiation force of focused ultrasonic beams. Such an ultrasonic radiation force is induced deep within the muscle by a conventional ultrasonic probe and the resulting shear waves are then imaged with the same probe (5 MHz) at an ultra-fast framerate (up to 5000 frames/s). Local tissue velocity maps are obtained with a conventional speckle tracking technique and provide a full movie of the shear wave propagation through the entire muscle. Shear wave group velocities are then estimated using a time of flight algorithm. This approach provides a complete set of quantitative and in vivo parameters describing the muscle’s mechanical properties as a function of active voluntary contraction as well as passive extension of healthy volunteers. Anisotropic properties are also estimated by tilting the probe head with respects to the main muscular fibers direction. Finally, the dispersion of the shear waves is studied for these different configurations and shear modulus and shear viscosity are quantitatively assessed assuming the viscoelastic Voigt’s model. (E-mail: jl.gennisson@espci.fr)     

Completely computer-focused ultrasound imaging. First clinical imaging results

Completely computer-focused ultrasound imaging has been achieved using the UHB (ultrasound holographic B) method. This is a synthetic aperture method that combines ultrasonic holography and the conventional B-scan method. A wide-angle ultrasound burst (4 MHz) is transmitted into the object and the reflected echoes are measured as a function of the propagation time, but both the amplitude and phase angle are recorded, giving multiple one-dimensional holograms in a cross-sectional plane. This UHB data is rearranged to obtain one-dimensional wave fields, which represent the wave fronts reflected from each depth. The image is then reconstructed by propagating these wave fields backward to their original positions on the image using Fourier transform, a spectrum shift theorem, and inverse Fourier transform. The whole UHB image is obtained by calculating the intensity lines from these wave fields and by scanning these lines one by on the cathode ray tube (CRT) monitor. Following extensive laboratory testing with single and multielement transducers, special 32- and 64-element linear array transducers were fabricated, as was computer software capable of producing a UHB image in 40 seconds. Tissue imaging tests followed by clinical imaging of 30 patients showed that images obtained with this prototype compared favorably with those obtained by state-of-the-art conventional ultrasound scanners. The potential advantages of the new method are enhanced lateral resolution and the incorporation of phase information in tissue characterization. This would be important in diagnostic and intraoperative, especially neurosurgical, imaging.     

Feasibility of optical coherence elastography measurements of shear wave propagation in homogeneous tissue equivalent phantoms

In this work, we explored the potential of measuring shear wave propagation using optical coherence elastography (OCE) based on a swept-source optical coherence tomography (OCT) system. Shear waves were generated using a 20 MHz piezoelectric transducer (circular element 8.5 mm diameter) transmitting sine-wave bursts of 400 μs, synchronized with the OCT swept source wavelength sweep. The acoustic radiation force (ARF) was applied to two gelatin phantoms (differing in gelatin concentration by weight, 8% vs. 14%). Differential OCT phase maps, measured with and without the ARF, demonstrate microscopic displacement generated by shear wave propagation in these phantoms of different stiffness. We present preliminary results of OCT derived shear wave propagation velocity and modulus, and compare these results to rheometer measurements. The results demonstrate the feasibility of shear wave OCE (SW-OCE) for high-resolution microscopic homogeneous tissue mechanical property characterization.     

Shear Wave Speed Estimation Using Reverberant Shear Wave Fields: Implementation and Feasibility Studies

Elastography is a modality that estimates tissue stiffness and, thus, provides useful information for clinical diagnosis. Attention has focused on the measurement of shear wave propagation; however, many methods assume shear wave propagation is unidirectional and aligned with the lateral imaging direction. Any deviations from the assumed propagation result in biased estimates of shear wave speed. To address these challenges, directional filters have been applied to isolate shear waves with different propagation directions. Recently, a new method was proposed for tissue stiffness estimation involving creation of a reverberant shear wave field propagating in all directions within the medium. These reverberant conditions lead to simple solutions, facile implementation and rapid viscoelasticity estimation of local tissue. In this work, this new approach based on reverberant shear waves was evaluated and compared with another well-known elastography technique using two calibrated elastic and viscoelastic phantoms. Additionally, the clinical feasibility of this technique was analyzed by assessing shear wave speed in human liver and breast tissues, in vivo. The results indicate that it is possible to estimate the viscoelastic properties in each scanned medium. Moreover, a better approach to estimation of shear wave speed was obtained when only the phase information was taken from the reverberant waves, which is equivalent to setting all magnitudes within the bandpass equal to unity: an idealization of a perfectly isotropic reverberant shear wave field.     

Shear Wave Elastography Quantification of Blood Elasticity During Clotting

Deep venous thrombosis (DVT) affects millions of people worldwide. A fatal complication occurs when the thrombi detach and create a pulmonary embolism. The diagnosis and treatment of DVT depends on clot's age. The elasticity of thrombi is closely related to its age. Blood was collected from pigs and anticoagulated using ethylenediaminetetraacetic acid (EDTA). Coagulation was initiated using calcium ions. Supersonic shear wave imaging was used to generate shear waves using 100 μs tone bursts of 8 MHz. Tracking of the shear waves was done by ultrafast imaging. Postprocessing of the data was done using Matlab^®. Two-dimensional (2-D) maps of elasticity were obtained by calculating the speed of shear wave propagation. Elasticity varied with time from around 50 Pa at coagulation to 1600 Pa at 120 min after which the elasticity showed a natural decreased (17%) because of thrombolytic action of plasmin. Ejection of the serum from the clot showed a significant decrease in the elasticity of the clot next to the liquid pool (65% decrease), corresponding to the detachment of the clot from the beaker wall. The use of a thrombolytic agent (Urokinase) on the coagulated blood decreased the shear elasticity close to the point of injection, which varied with time and distance. Supersonic imaging proved to be useful mapping the 2-D clot's elasticity. It allowed the visualization of the heterogeneity of mechanical properties of thrombi and has potential use in predicting thrombi breakage as well as in monitoring thrombolytic therapy.     

Analysis of Transient Shear Wave in Lossy Media

The propagation of shear waves from impulsive forces is an important topic in elastography. Observations of shear wave propagation can be obtained with numerous clinical imaging systems. Parameter estimations of the shear wave speed in tissues, and more generally the viscoelastic parameters of tissues, are based on some underlying models of shear wave propagation. The models typically include specific choices of the spatial and temporal shape of the impulsive force and the elastic or viscoelastic properties of the medium. In this work, we extend the analytical treatment of 2-D shear wave propagation in a biomaterial. The approach applies integral theorems relevant to the solution of the generalized Helmholtz equation, and does not depend on a specific rheological model of the tissue's viscoelastic properties. Estimators of attenuation and shear wave speed are derived from the analytical solutions, and these are applied to an elastic phantom, a viscoelastic phantom and in vivo liver using a clinical ultrasound scanner. In these samples, estimated shear wave group velocities ranged from 1.7?m/s in the liver to 2.5?m/s in the viscoelastic phantom, and these are lower-bounded by independent measurements of phase velocity.     

Monitoring thermally-induced lesions with supersonic shear imaging

Thermally-induced lesions are generally stiffer than surrounding tissues. We propose here to use the supersonic shear imaging technique (SSI) for monitoring high-intensity focused ultrasound (HIFU) therapy. This new elasticity imaging technique is based on remotely creating shear sources using an acoustic radiation force at different locations in the medium. In these experiments, an HIFU probe is used to generate lesions in fresh tissue samples. A diagnostic transducer, controlled by our ultrafast scanner, is located in the therapeutic probe focal plane. It is used for both generating the shear waves and imaging the resulting propagation at frame rates reaching 5,000 images/s. Movies of the shear wave propagation can be computed off-line. The therapeutic and imaging sequences are interleaved and a set of wave propagation movies is performed during the heating process. From each movie, elasticity estimations have been performed using an inversion algorithm. It demonstrates the feasibility of detecting and quantifying the hardness of HIFU-induced lesions using SSI.     

Cardiac Shear Wave Velocity Detection in the Porcine Heart

Cardiac muscle stiffness can potentially be estimated non-invasively with shear wave elastography. Shear waves are present on the septal wall after mitral and aortic valve closure, thus providing an opportunity to assess stiffness in early systole and early diastole. We report on the shear wave recordings of 22 minipigs with high-frame-rate echocardiography. The waves were captured with 4000 frames/s using a programmable commercial ultrasound machine. The wave pattern was extracted from the data through a local tissue velocity estimator based on one-lag autocorrelation. The wave propagation velocity was determined with a normalized Radon transform, resulting in median wave propagation velocities of 2.2 m/s after mitral valve closure and 4.2 m/s after aortic valve closure. Overall the velocities ranged between 0.8 and 6.3 m/s in a 95% confidence interval. By dispersion analysis we found that the propagation velocity only mildly increased with shear wave frequency.     

Quantitative Viscoelasticity Mapping of Human Liver Using Supersonic Shear Imaging: Preliminary In Vivo Feasability Study

This paper demonstrates the feasibility of in vivo quantitative mapping of liver viscoelasticity using the concept of supersonic shear wave imaging. This technique is based on the combination of a radiation force induced in tissues by focused ultrasonic beams and a very high frame rate ultrasound imaging sequence capable of catching in real time the transient propagation of resulting shear waves. The local shear wave velocity is recovered using a dedicated time-of-flight estimation technique and enables the 2-D quantitative mapping of shear elasticity. This imaging modality is performed using a conventional ultrasound probe during a standard intercostal ultrasonographic examination. Three supersonic shear imaging (SSI) sequences are applied successively in the left, middle and right parts of the 2-D ultrasonographic image. Resulting shear elasticity images in the three regions are concatenated to provide the final image covering the entire region-of-interest. The ability of the SSI technique to provide a quantitative and local estimation of liver shear modulus with a millimetric resolution is proven in vivo on 15 healthy volunteers. Liver moduli extracted from in vivo data from healthy volunteers are consistent with those reported in the literature (Young's modulus ranging from 4 to 7.5 kPa). Moreover, liver stiffness estimation using the SSI mode is shown to be fast (less than one second), repeatable (5.7% standard deviation) and reproducible (6.7% standard deviation). This technique, used as a complementary tool for B-mode ultrasound, could complement morphologic information both for fibrosis staging and hepatic lesions imaging (E-mail: jl.gennisson@espci.fr).     

Ultrasonic Propagation in a Dental Implant

Ultrasound techniques can be used to characterize and stimulate dental implant osseointegration. However, the interaction between an ultrasonic wave and the implant-bone interface (IBI) remains unclear. This study—combining experimental and numerical approaches—investigates the propagation of an ultrasonic wave in a dental implant by assessing the amplitude of the displacements along the implant axis. An ultrasonic transducer was excited in a transient regime at 10 MHz. Laser interferometric techniques were employed to measure the amplitude of the displacements, which varied 3.2–8.9 nm along the implant axis. The results demonstrated the propagation of a guided wave mode along the implant axis. The velocity of the first arriving signal was equal to 2110 m.s^–1, with frequency components lower than 1 MHz, in agreement with numerical results. Investigating guided wave propagation in dental implants should contribute to improved methods for the characterization and stimulation of the IBI.     

Role of Multiparametric Ultrasound in Evaluating Hepatic Acute Graft-versus-Host Disease: An Animal Study

ObjectiveHepatic acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is one of the leading causes of early non-recurrent death. The current diagnosis is based mainly based on clinical diagnosis, and there is a lack of non-invasive quantitative diagnosis methods. We propose a multiparametric ultrasound (MPUS) imaging method and explore its effectiveness in evaluating hepatic aGVHD.MethodsIn this study, 48 female Wistar rats were used as receptors and 12 male Fischer 344 rats were used as donors for allo-HSCT to establish aGVHD models. After transplantation, 8 rats were randomly selected for ultrasonic examination weekly, including color Doppler ultrasound, contrast-enhanced ultrasound (CEUS) and shear wave dispersion (SWD) imaging. The values of nine ultrasonic parameters were obtained. Hepatic aGVHD was subsequently diagnosed by histopathological analysis. A classification model for predicting hepatic aGVHD was established using principal component analysis and support vector machines.ResultsAccording to the pathological results, the transplanted rats were categorized into the hepatic aGVHD and non-GVHD (nGVHD) groups. All parameters obtained by MPUS differed statistically between the two groups. The first three contributing percentages of principal component analysis results were resistivity index, peak intensity and shear wave dispersion slope, respectively. The accuracy of classifying aGVHD and nGVHD using support vector machines reached 100%. The accuracy of the multiparameter classifier was significantly higher than that of the single parameter.ConclusionThe MPUS imaging method has proven to be useful in detecting hepatic aGVHD.     

Quantitative assessment of breast lesion viscoelasticity: initial clinical results using supersonic shear imaging

Abtract This paper presents an initial clinical evaluation of in vivo elastography for breast lesion imaging using the concept of supersonic shear imaging. This technique is based on the combination of a radiation force induced in tissue by an ultrasonic beam and an ultrafast imaging sequence capable of catching in real time the propagation of the resulting shear waves. The local shear wave velocity is recovered using a time-offlight technique and enables the 2-D mapping of shear elasticity. This imaging modality is implemented on a conventional linear probe driven by a dedicated ultrafast echographic device. Consequently, it can be performed during a standard echographic examination. The clinical investigation was performed on 15 patients, which corresponded to 15 lesions (4 cases BI-RADS 3, 7 cases BI-RADS 4 and 4 cases BI-RADS 5). The ability of the supersonic shear imaging technique to provide a quantitative and local estimation of the shear modulus of abnormalities with a millimetric resolution is illustrated on several malignant (invasive ductal and lobular carcinoma) and benign cases (fibrocystic changes and viscous cysts). In the investigated cases, malignant lesions were found to be significantly different from benign solid lesions with respect to their elasticity values. Cystic lesions have shown no shear wave propagate at all in the lesion (because shear waves do not propage in liquid). These preliminary clinical results directly demonstrate the clinical feasibility of this new elastography technique in providing quantitative assessment of relative stiffness of breast tissues. This technique of evaluating tissue elasticity gives valuable information that is complementary to the B-mode morphologic information. More extensive studies are necessary to validate the assumption that this new mode potentially helps the physician in both false-positive and false-negative rejection. (E-mail: Mickael.tanter@espci.fr).     

A Method for Characterization of Tissue Elastic Properties Combining Ultrasonic Computed Tomography With Elastography

Objective. The correlation between various diseases and the change in the local mechanical properties of soft tissues has been long known. Over the past 20 years, there have been increasing research efforts to characterize mechanical properties of biological tissues using ultrasonic elastography. However, most of these works were based on characterization of only 1 type of waves (longitudinal or shear). The goal of this work was to devise a comprehensive ultrasound‐based imaging method capable of measuring elastic parameters by combining both backscattered elastography and through‐transmitted ultrasonic computed tomography. Methods. Our suggested technique provides measurements of both longitudinal and shear wave velocities. This enables the noninvasive computation of several tissue elasticity parameters such as Young's and shear moduli, Poisson's ratio, and, more importantly, the bulk modulus, the determination of which requires both wave velocities. Four different phantom types were examined: agar‐gelatin–based phantoms and porcine fat tissue, turkey breast tissue, and bovine liver tissue in vitro specimens. The values of Young's modulus, the shear modulus, and Poisson's ratio were estimated and were consistent with values published in the literature. Results. The average bulk modulus values of the phantoms ± SD were 2.83 ± 0.001, 2.25 ± 0.01, 2.48 ± 0.01, and 2.53 ± 0.02 GPa, respectively. A statistically significant difference (P < .001) in the values of the bulk modulus of the different phantoms was found. Conclusions. The bulk modulus is suitable for differentiation between different tissue types. The obtained results show the feasibility of using a comprehensive ultrasonic imaging technique for noninvasive quantitative tissue characterization.     

Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics

Shear wave elasticity imaging (SWEI) is a new approach to imaging and characterizing tissue structures based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. SWEI provides the physician with a virtual “finger” to probe the elasticity of the internal regions of the body. In SWEI, compared to other approaches in elasticity imaging, the induced strain in the tissue can be highly localized, because the remotely induced shear waves are attenuated fully within a very limited area of tissue in the vicinity of the focal point of a focused ultrasound beam. SWEI may add a new quality to conventional ultrasonic imaging or magnetic resonance imaging. Adding shear elasticity data (“palpation information”) by superimposing color-coded elasticity data over ultrasonic or magnetic resonance images may enable better differentiation of tissues and further enhance diagnosis. This article presents a physical and mathematical basis of SWEI with some experimental results of pilot studies proving feasibility of this new ultrasonic technology. A theoretical model of shear oscillations in soft biological tissue remotely induced by the radiation force of focused ultrasound is described. Experimental studies based on optical and magnetic resonance imaging detection of these shear waves are presented. Recorded spatial and temporal profiles of propagating shear waves fully confirm the results of mathematical modeling. Finally, the safety of the SWEI method is discussed, and it is shown that typical ultrasonic exposure of SWEI is significantly below the threshold of damaging effects of focused ultrasound.     

High-Resolution Elastography for Thin-Layer Mechanical Characterization: Toward Skin Investigation

Interest in elasticity estimation for thin layers is increasing because of the various potential applications, including dermatology and cosmetology. In this context, we propose a dedicated elastographic system using 1-D high-frequency transient elastography (HF-TE) to estimate the 1-D Young's modulus through the dermis and hypodermis, which are the two human skin layers of interest in this study. An experimental validation of the HF-TE method was first carried out on two homogeneous tissue-mimicking hard and soft phantoms. The Young's modulus values obtained in these phantoms were compared with those obtained by two complementary shear wave propagation techniques: shear wave-induced resonance elastography (SWIRE) and supersonic shear imaging (SSI). A third two-layer thin phantom, with mechanical properties similar to those of skin, was used to validate the ability of HF-TE to distinguish layers and measure elasticity. Finally, preliminary in vivo experiments conducted on forearm and cheek skin revealed the promising performance of HF-TE in measuring elasticity in the dermis and hypodermis.     

Longitudinal and shear mode ultrasound propagation in human skull bone

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.     

Acoustic Waves in Medical Imaging and Diagnostics

Up until about two decades ago acoustic imaging and ultrasound imaging were synonymous. The term ultrasonography, or its abbreviated version sonography, meant an imaging modality based on the use of ultrasonic compressional bulk waves. Beginning in the 1990s, there started to emerge numerous acoustic imaging modalities based on the use of a different mode of acoustic wave: shear waves. Imaging with these waves was shown to provide very useful and very different information about the biological tissue being examined. We discuss the physical basis for the differences between these two basic modes of acoustic waves used in medical imaging and analyze the advantages associated with shear acoustic imaging. A comprehensive analysis of the range of acoustic wavelengths, velocities and frequencies that have been used in different imaging applications is presented. We discuss the potential for future shear wave imaging applications.     

High-frequency backscatter and attenuation measurements of selected bovine tissues between 10 and 30 MHz

There are now diagnostic ultrasonic imaging devices that operate at very high frequencies (VHF) of 20 MHz and beyond for clinical applications in ophthalmology, dermatology, vascular surgery, endoluminal imaging and small animal imaging. To be able to better interpret these images and to further the development of these devices, knowledge of ultrasonic attenuation and scattering of biological tissues in this frequency range is crucial. Attenuation and backscatter coefficients (BSCs) of bovine tissues in the frequency range of 10 to 30 MHz were measured, respectively, using a standard substitution method for attenuation measurements and a modified narrow-band substitution method for scattering measurements. A modified substitution method for scattering measurements has to be used at high frequencies because unfocused transducers due to their decreased sensitivity cannot be used in the simple substitution method. In the modified method, the flat reflector is substituted by a particulate reference medium whose BSC is well-known and documented; in this case, a red cell suspension. In this paper, experimental results on BSC and attenuation coefficient measured between 10 and 30 MHz are reported. The frequency dependence of backscatter of the selected bovine tissues ranges from 2.4 to 3.5, whereas attenuation is observed to be still approximately linearly proportional to frequency. The BSC measured with the modified method is in good agreement with those obtained with the standard method between 10 and 20 MHz.     

超高速超声成像的研究进展

近年来发展迅速的超高速超声成像可获得高达数千至上万帧/秒的帧频,具有绝佳的时间分辨力,可以实现传统超声的帧频无法获得的成像结果。本文对超高速成像的基本原理及其目前在剪切波弹性成像、多普勒成像、心血管成像、造影成像等领域的应用进展进行综述。     

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. (E-mail: mathieu.couade@gmail.com)