Estimation of polyvinyl alcohol cryogel mechanical properties with four ultrasound elastography methods and comparison with gold standard testings

Tissue-mimicking phantoms are very useful in the field of tissue characterization and essential in elastography for the purpose of validating motion estimators. This study is dedicated to the characterization of polyvinyl alcohol cryogel (PVA-C) for these types of applications. A strict fabrication procedure was defined to optimize the reproducibility of phantoms having a similar elasticity. Following mechanical stretching tests, the phantoms were used to compare the accuracy of four different elastography methods. The four methods were based on a one-dimensional (1-D) scaling factor estimation, on two different implementations of a 2-D Lagrangian speckle model estimator (quasistatic elastography methods), and on a 1-D shear wave transient elastography technique (dynamic method). Young's modulus was investigated as a function of the number of freeze-thaw cycles of PVA-C, and of the concentration of acoustic scatterers. Other mechanical and acoustic parameters-such as the speed of sound, shear wave velocity, mass density, and Poisson's ratio-also were assessed. The Poisson's ratio was estimated with good precision at 0.499 for all samples, and the Young's moduli varied in a range of 20 kPa for one freeze-thaw cycle to 600 kPa for 10 cycles. Nevertheless, above six freeze-thaw cycles, the results were less reliable because of sample geometry artifacts. However, for the samples that underwent less than seven freeze-thaw cycles, the Young's moduli estimated with the four elastography methods showed good matching with the mechanical tensile tests with a regression coefficient varying from 0.97 to 1.07, and correlations R2 varying from 0.93 to 0.99, depending on the method.     

Assessment of elastic parameters of human skin using dynamic elastography

Sonoelastography and transient elastography are two ultrasound-based techniques that facilitate noninvasive characterization of the viscoelastic properties of soft tissues by investigating their response to shear mechanical excitation. Young's modulus is the principle assessment parameter. Because it defines local tissue stiffness, it is of major interest for the medical imaging and cosmetic industries as it could replace subjective palpation by yielding local, quantitative information. In this paper, we describe a new high-resolution device capable of measuring local Young's modulus in very thin layers (1-5 mm) and devoted to the in vivo evaluation of the elastic properties of human skin. It uses an ultrasonic probe (50 MHz) for tracking the displacements induced by a 300 Hz shear wave generated by a ring surrounding the transducer. The displacements are measured using a conventional cross-correlation technique between successive ultrasonic back-scattered echoes. First, this noninvasive technique has been experimentally proven to be accurate for investigating elasticity in different skin-mimicking phantoms. Second, data were acquired in vivo on human forearms. As expected, Young's modulus was found to be higher in the dermis than in the hypodermis and other soft tissues.     

Monitored steady-state excitation and recovery (MSSER) radiation force imaging using viscoelastic models

Acoustic radiation force imaging methods distinguish tissue structure and composition by monitoring tissue responses to applied radiation force excitations. Although these responses are a complex, multidimensional function of the geometric and viscoelastic nature of tissue, simplified discrete biomechanical models offer meaningful insight to the physical phenomena that govern induced tissue motion. Applying Voigt and standard linear viscoelastic tissue models, we present a new radiation force technique - monitored steady-state excitation and recovery (MSSER) imaging - that tracks both steady-state displacement during prolonged force application and transient response following force cessation to estimate tissue mechanical properties such as elasticity and viscosity. In concert with shear wave elasticity imaging (SWEI) estimates for Young's modulus, MSSER methods are useful for estimating tissue mechanical properties independent of the applied force magnitude. We test our methods in gelatin phantoms and excised pig muscle, with confirmation through mechanical property measurement. Our results measured 10.6 kPa, 14.7 kPa, and 17.1 kPa (gelatin) and 122.4 kPa (pig muscle) with less than 10% error. This work demonstrates the feasibility of MSSER imaging and merits further efforts to incorporate relevant mechanical tissue models into the development of novel radiation force imaging techniques.     

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.     

On the effects of reflected waves in transient shear wave elastography

In recent years, novel quantitative techniques have been developed to provide noninvasive and quantitative stiffness images based on shear wave propagation. Using radiation force and ultrafast ultrasound imaging, the supersonic shear imaging technique allows one to remotely generate and follow a transient plane shear wave propagating in vivo in real time. The tissue shear modulus, i.e., its stiffness, can then be estimated from the shear wave local velocity. However, because the local shear wave velocity is estimated using a time-of- flight approach, reflected shear waves can cause artifacts in the estimated shear velocity because the incident and reflected waves propagate in opposite directions. Such effects have been reported in the literature as a potential drawback of elastography techniques based on shear wave speed, particularly in the case of high stiffness contrasts, such as in atherosclerotic plaque or stiff lesions. In this letter, we present our implementation of a simple directional filter, previously used for magnetic resonance elastography, which separates the forward- and backward-propagating waves to solve this problem. Such a directional filter could be applied to many elastography techniques based on the local estimation of shear wave speed propagation, such as acoustic radiation force imaging (ARFI), shearwave dispersion ultrasound vibrometry (SDUV), needle-based elastography, harmonic motion imaging, or crawling waves when the local propagation direction is known and high-resolution spatial and temporal data are acquired.     

Lesion generation through ribs using histotripsy therapy without aberration correction

This study investigates the feasibility of using high-intensity pulsed therapeutic ultrasound, or histotripsy, to non-invasively generate lesions through the ribs. Histotripsy therapy mechanically ablates tissue through the generation of a cavitation bubble cloud, which occurs when the focal pressure exceeds a certain threshold. We hypothesize that histotripsy can generate precise lesions through the ribs without aberration correction if the main lobe retains its shape and exceeds the cavitation initiation threshold and the secondary lobes remain below the threshold. To test this hypothesis, a 750-kHz focused transducer was used to generate lesions in tissue-mimicking phantoms with and without the presence of rib aberrators. In all cases, 8000 pulses with 16 to 18 MPa peak rarefactional pressure at a repetition frequency of 100 Hz were applied without aberration correction. Despite the high secondary lobes introduced by the aberrators, high-speed imaging showed that bubble clouds were generated exclusively at the focus, resulting in well-confined lesions with comparable dimensions. Collateral damage from secondary lobes was negligible, caused by single bubbles that failed to form a cloud. These results support our hypothesis, suggesting that histotripsy has a high tolerance for aberrated fields and can generate confined focal lesions through rib obstacles without aberration correction.     

Ultrafast compound imaging for 2-D motion vector estimation: application to transient elastography

This paper describes a new technique for two-dimensional (2-D) imaging of the motion vector at a very high frame rate with ultrasound. Its potential is experimentally demonstrated for transient elastography. But, beyond this application, it also could be promising for color flow and reflectivity imaging. To date, only axial displacements induced in human tissues by low-frequency vibrators were measured during transient elastography. The proposed technique allows us to follow both axial and lateral displacements during the shear wave propagation and thus should improve Young's modulus image reconstruction. The process is a combination of several ideas well-known in ultrasonic imaging: ultra-fast imaging, multisynthetic aperture beamforming, 1-D speckle tracking, and compound imaging. Classical beamforming in the transmit mode is replaced here by a single plane wave insonification increasing the frame rate by at least a factor of 128. The beamforming is achieved only in the receive mode on two independent subapertures. Comparison of successive frames by a classical 1-D speckle tracking algorithm allows estimation of displacements along two different directions linked to the subapertures beams. The variance of the estimates is finally improved by tilting the emitting plane wave at each insonification, thus allowing reception of successive decorrelated speckle patterns.     

Bubble-based acoustic radiation force elasticity imaging

Acoustic radiation force is applied to bubbles generated by laser-induced optical breakdown (LIOB) to study viscoelastic properties of the surrounding medium. In this investigation, femtosecond laser pulses are focused in the volume of gelatin phantoms of different concentrations to form bubbles. A two-element confocal ultrasonic transducer generates acoustic radiation force on individual bubbles while monitoring their displacement within a viscoelastic medium. Tone burst pushes of varying duration have been applied by the outer element at 1.5 MHz. The inner element receives pulse-echo recordings at 7.44 MHz before, during, and after the excitation bursts, and crosscorrelation processing is performed offline to monitor bubble position. Maximum bubble displacements are inversely related to the Young's moduli for different gel phantoms, with a maximum bubble displacement of over 200 microm in a gel phantom with a Young's modulus of 1.7 kPa. Bubble displacements scale with the applied acoustic radiation force and displacements can be normalized to correct for differences in bubble size. Exponential time constants for bubble displacement curves are independent of bubble radius and follow a decreasing trend with the Young's modulus of the surrounding medium. These results demonstrate the potential for bubble-based acoustic radiation force methods to measure tissue viscoelastic properties.     

超声编码激励在瞬时弹性成像检测中的应用

瞬时弹性(Transient Elastography,TE)成像广泛应用于肝硬化研究。然而,在临床应用中,对于肥胖病人,该方法很难实现对深度位置的瞬时剪切波进行检测。研究了将超声编码激励应用于瞬时弹性成像剪切波检测的可行性,选用7位巴克码进行编码检测研究。通过剪切波信噪比和检测穿透力两个指标对编码检测与传统短脉冲检测结果进行量化和对比。弹性仿体实验表明,编码检测可以提供比传统短脉冲检测更高的剪切波信噪比和检测深度。离体猪肝实验表明将编码激励应用于组织检测时同样可以实现高信噪比剪切波检测。这些结果表明编码检测应用于瞬时弹性成像检测是可行的,可以增加其检测深度。     

Application of 1-D transient elastography for the shear modulus assessment of thin-layered soft tissue: comparison with supersonic shear imaging technique

Elasticity estimation of thin-layered soft tissues has gained increasing interest propelled by medical applications like skin, corneal, or arterial wall shear modulus assessment. In this work, the authors propose one-dimensional transient elastography (1DTE) for the shear modulus assessment of thin-layered soft tissue. Experiments on three phantoms with different elasticities and plate thicknesses were performed. First, using 1DTE, the shear wave speed dispersion curve inside the plate was obtained and validated with finite difference simulation. No dispersive effects were observed and the shear wave speed was directly retrieved from time-of-flight measurements. Second, the supersonic shear imaging (SSI) technique (considered to be a gold standard) was performed. For the SSI technique, the propagating wave inside the plate is guided as a Lamb wave. Experimental SSI dispersion curves were compared with finite difference simulation and fitted using a generalized Lamb model to retrieve the plate bulk shear wave speed. Although they are based on totally different mechanical sources and induce completely different diffraction patterns for the shear wave propagation, the 1DTE and SSI techniques resulted in similar shear wave speed estimations. The main advantage of the 1DTE technique is that bulk shear wave speed can be directly retrieved without requiring a dispersion model.     

High speed imaging of bubble clouds generated in pulsed ultrasound cavitational therapy--histotripsy

Our recent studies have demonstrated that mechanical fractionation of tissue structure with sharply demarcated boundaries can be achieved using short (< 20 micros), high intensity ultrasound pulses delivered at low duty cycles. We have called this technique histotripsy. Histotripsy has potential clinical applications where noninvasive tissue fractionation and/or tissue removal are desired. The primary mechanism of histotripsy is thought to be acoustic cavitation, which is supported by a temporally changing acoustic backscatter observed during the histotripsy process. In this paper, a fast-gated digital camera was used to image the hypothesized cavitating bubble cloud generated by histotripsy pulses. The bubble cloud was produced at a tissue-water interface and inside an optically transparent gelatin phantom which mimics bulk tissue. The imaging shows the following: (1) Initiation of a temporally changing acoustic backscatter was due to the formation of a bubble cloud; (2) The pressure threshold to generate a bubble cloud was lower at a tissue-fluid interface than inside bulk tissue; and (3) at higher pulse pressure, the bubble cloud lasted longer and grew larger. The results add further support to the hypothesis that the histotripsy process is due to a cavitating bubble cloud and may provide insight into the sharp boundaries of histotripsy lesions.     

Visualizing the radial and circumferential strain distribution within vessel phantoms using synthetic-aperture ultrasound elastography

Noninvasive elastography (NIVE) produces elastograms that are difficult to interpret because NIVE visualizes strain in the transducer coordinate system. In this paper, we hypothesized that transforming normal and shear strain elastograms to the vessel coordinate system will produce better strain elastograms. To corroborate this hypothesis, we acquired synthetic-aperture (SA) ultrasound data from simulated and physical vessel phantoms. In both studies, SA echo frames were reconstructed from data acquired with a sparse transducer array. The simulation study was performed with homogeneous and heterogenous phantoms, but in the experimental study we used a modified ultrasound scanner to acquire SA data from homogeneous (n = 1) and heterogeneous (n = 3) vessel phantoms. Axial and lateral displacements were estimated by performing two-dimensional cross-correlation analysis on the beamformed RF echo frames. We generated radial and circumferential strain elastograms by transforming normal and shear strain elastograms to the vessel coordinate system. The results revealed: 1) radial and circumferential strain elastograms acquired from simulated data had a relative root mean squared error on the order of 0.1%; 2) experimentally acquired radial and circumferential strain elastograms had elastographic contrast-to-noise ratio (CNRe) between 10 and 40 dB, and elastographic signal-to-noise ratio (SNRe) between 10 and 35 dB, depending on the number of active transmission elements employed during imaging; 3) radial and circumferential strain elastograms produced with fewer than 8 active transmission elements were inferior to those computed with a greater number of active elements; and 4) plaques were evident in the strain elastograms, except in those obtained with the sparsest transducer array. This study demonstrated that a syntheticaperture ultrasound system could visualize radial and circumferential strain noninvasively.     

Phantom materials for elastography

Acoustic and mechanical properties are reported for gelatin materials used to construct tissue-like phantoms for elasticity imaging (elastography). A device and procedure for measuring elastic properties are described. The measured compression forces were comparable to results obtained from finite element analysis when linear elastic media are assumed. Also measured were the stress relaxation, temporal stability, and melting point of the materials. Aldehyde concentration was used to increase the stiffness of the gelatin by controlling the amount of collagen cross-linking. A broad range of tissue-like elastic properties was achieved with these materials, although gels continued to stiffen for several weeks. The precision for elastic modulus measurements ranged from less than 0.1% for 100 kPa samples to 8.9% for soft (<10 kPa), sticky samples     

Shear modulus imaging with 2-D transient elastography

In previous work, we have shown that time-resolved 2-D transient elastography is a promising technique for characterizing the elasticity of soft tissues. It involves the measurement of the displacements induced by the propagation of low frequency (LF) pulsed shear waves in biological tissues. In this paper, we present a novel apparatus that contains a LF vibrating device surrounding a linear array of 128 ultrasonic transducers that performs ultrafast ultrasonic imaging (up to 10,000 frames/s) and that is able to follow in real time the propagation of a LF shear wave in the human body. The vibrating device is made of two rods, fixed to electromagnetic vibrators, that produce in the ultrasonic image area a large amplitude shear wave. The geometry has been chosen both to enhance the sensitivity and to create a quasi linear shear wave front in the imaging plane. An inversion algorithm is used to recover the shear modulus map from the spatio-temporal data, and the first experimental results obtained from tissue-equivalent materials are presented.     

Active focal zone sharpening for high-precision treatment using histotripsy

The goal of this study is to develop a focal zone sharpening strategy that produces more precise lesions for pulsed cavitational ultrasound therapy, or histotripsy. Precise and well-confined lesions were produced by locally suppressing cavitation in the periphery of the treatment focus without affecting cavitation in the center. The local suppression of cavitation was achieved using cavitation nuclei preconditioning pulses to actively control cavitation in the periphery of the focus. A 1-MHz 513-element therapeutic array was used to generate both the therapy and the nuclei preconditioning pulses. For therapy, 10-cycle bursts at 100-Hz pulse repetition frequency with P-/P+ pressure of 21/76 MPa were delivered to the geometric focus of the therapeutic array. For nuclei preconditioning, a different pulse was delivered to an annular region immediately surrounding the focus before each therapy pulse. A parametric study on the effective pressure, pulse duration, and delivery time of the preconditioning pulse was conducted in red blood cell-gel phantoms, where cavitational damage was indicated by the color change resulting from local cell lysis. Results showed that a short-duration (20 μs) preconditioning pulse at a medium pressure (P-/P+ pressure of 7.2/13.6 MPa) delivered shortly before (30 μs) the therapy pulse substantially suppressed the peripheral damage by 77 ± 13% while complete fractionation in the focal center was maintained. High-speed imaging of the bubble cloud showed a substantial decrease in the maximum width of the bubble cloud by 48 ± 24% using focal zone sharpening. Experiments in ex vivo livers confirmed that highly confined lesions were produced in real tissues as well as in the phantoms. This study demonstrated the feasibility of active focal zone sharpening using cavitation nuclei preconditioning, allowing for increased treatment precision compared with the natural focal width of the therapy transducer.     

Monitoring of thermal therapy based on shear modulus changes: I. shear wave thermometry

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is today hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to the 2-D mapping of temperature changes during HIFU treatments. This new concept of shear wave thermometry is experimentally implemented here using conventional ultrasonic imaging probes. HIFU treatment and monitoring were, respectively, performed using a confocal setup consisting of a 2.5-MHz single-element transducer focused at 30 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Thermocouple measurements and ultrasound-based thermometry were used as a gold standard technique and were combined with SWI on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created using 100-μs pushing beams at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Elasticity and temperature mapping was achieved every 3 s, leading to realtime monitoring of the treatment. Tissue stiffness was found to decrease in the focal zone for temperatures up to 43°C. Ultrasound-based temperature estimation was highly correlated to stiffness variation maps (r2 = 0.91 to 0.97). A reversible calibration phase of the changes of elasticity with temperature can be made locally using sighting shots. This calibration process allows for the derivation of temperature maps from shear wave imaging. Compared with conventional ultrasound-based approaches, shear wave thermometry is found to be much more robust to motion artifacts.     

2-D high-frame-rate dynamic elastography using delay compensated and angularly compounded motion vectors: preliminary results

This paper describes a new ultrasound-based system for high-frame-rate measurement of periodic motion in 2-D for tissue elasticity imaging. Similarly to conventional 2-D flow vector imaging, the system acquires the RF signals from the region of interest at multiple steering angles. A custom sector subdivision technique is used to increase the temporal resolution while keeping the total acquisition time within the range suitable for real-time applications. Within each sector, 1-D motion is estimated along the beam direction. The intra- and inter-sector delays are compensated using our recently introduced delay compensation algorithm. In-plane 2-D motion vectors are then reconstructed from these delay-compensated 1-D motions. We show that Young's modulus images can be reconstructed from these 2-D motion vectors using local inversion algorithms. The performance of the system is validated quantitatively using a commercial flow phantom and a commercial elasticity phantom. At the frame rate of 1667 Hz, the estimated flow velocities with the system are in agreement with the velocity measured with a pulsed-wave Doppler imaging mode of a commercial ultrasound machine with manual angle correction. At the frame rate of 1250 Hz, phantom Young's moduli of 29, 6, and 54 kPa for the background, the soft inclusion, and the hard inclusion, are estimated to be 30, 11, and 53 kPa, respectively.     

Monitoring of thermal therapy based on shear modulus changes: II. Shear wave imaging of thermal lesions

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is currently hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to a precise mapping of the lesion. HIFU treatment and monitoring were respectively performed using a confocal setup consisting of a 2.5-MHz single element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Ultrasound-based strain imaging was combined with shear wave imaging on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created with pushing beams of 100 μs at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real-time monitoring of the treatment. When thermal damage occurs, tissue stiffness was found to increase up to 4-fold and strain imaging showed strong shrinkages that blur the temperature information. We show that strain imaging elastograms are not easy to interpret for accurate lesion characterization, but SWI provides a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave thermometry (SWT) developed in the companion paper allows mapping temperature with the same method. Combined SWT and shear wave imaging can map the lesion stiffening and temperature outside the lesion, which could be used to predict the eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be robust to motion and reliable in vivo on sheep muscle.     

Quantitative imaging of nonlinear shear modulus by combining static elastography and shear wave elastography

The study of new tissue mechanical properties such as shear nonlinearity could lead to better tissue characterization and clinical diagnosis. This work proposes a method combining static elastography and shear wave elastography to derive the nonlinear shear modulus by applying the acoustoelasticity theory in quasi-incompressible soft solids. Results demonstrate that by applying a moderate static stress at the surface of the investigated medium, and by following the quantitative evolution of its shear modulus, it is possible to accurately and quantitatively recover the local Landau (A) coefficient characterizing the shear nonlinearity of soft tissues.     

Influence of density, elasticity, and structure on ultrasound transmission through trabecular bone cylinders

The aim of this in vitro study is to evaluate the potentiality of quantitative ultrasound (QUS) to separate information on density, elasticity, and structure on specimens of trabecular bone. Fifteen cylinders of spongy bone extracted from equine vertebrae were progressively demineralized and subjected to QUS, micro computed tomography (muCT), Dual energy X-ray absorptiometry (DXA) at various mineralization levels. Eventually all cylinders underwent a compression test to calculate the Young's modulus. Correlation analysis shows that speed of sound (SOS) is strictly associated to bone mineral density (BMD), Young's modulus, and all muCT parameters except for degree of anisotropy (DA). Fast wave amplitude (FWA) is directly correlated with bone surface and total volume ratio (BS/TV) and trabecular separation (Tb Sp), and inversely correlated with trabecular number (Tb N). Because muCT parameters were strictly correlated to BMD and Young's modulus data, partial correlation analysis was performed between SOS, FWA, and structural and elastic data in order to eliminate the effect of density. SOS was significantly correlated to bone volume and total volume ratio (BV/TV), BS/TV, and Young's modulus, and FWA was significantly correlated to Tb Sp only. These results show that SOS is strongly influenced by volumetric mineral bone density and elastic modulus of the specimen, and FWA is mainly affected by trabecular separation independently on density. Therefore, SOS and FWA are able to provide different and complementary information, at least on trabecular bone samples.