Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and Kalman filter

A method using pulse echo ultrasound and the Kalman filter is developed for detecting submicron harmonic motion induced by ultrasonic radiation force. The method estimates the amplitude and phase of the motion at desired locations within a tissue region with high sensitivity. The harmonic motion generated by the ultrasound radiation force is expressed as extremely small oscillatory Doppler frequency shifts in the fast time (A-line) of ultrasound echoes, which are difficult to estimate. In slow time (repetitive ultrasound echoes) of the echoes, the motion also is presented as oscillatory phase shifts, from which the amplitude and phase of the harmonic motion can be estimated with the least mean squared error by Kalman filter. This technique can be used to estimate the traveling speed of a harmonic shear wave by tracking its phase changes during propagation. The shear wave propagation speed can be used to solve for the elasticity and viscosity of tissue as reported in our earlier study. Validation and in vitro experiments indicate that the method provides excellent estimations for very small (submicron) harmonic vibrations and has potential for noninvasive and quantitative stiffness measurements of tissues such as artery.     

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.     

Propagation of spontaneously actuated pulsive vibration in human heart wall and in vivo viscoelasticity estimation

Though myocardial viscoelasticity is essential in the evaluation of heart diastolic properties, it has never been noninvasively measured in vivo. By the ultrasonic measurement of the myocardial motion, we have already found that some pulsive waves are spontaneously excited by aortic-valve closure (AVC) at end-systole (T0). These waves may serve as an ideal source of the intrinsic heart sound caused by AVC. In this study, using a sparse sector scan, in which the beam directions are restricted to about 16, the pulsive waves were measured almost simultaneously at about 160 points set along the heart wall at a sufficiently high frame rate. The consecutive spatial phase distributions, obtained by the Fourier transform of the measured waves, clearly revealed wave propagation along the heart wall for the first time. The propagation time of the wave along the heart wall is very small (namely, several milliseconds) and cannot be measured by conventional equipment. Based on this phenomenon, we developed a means to measure the myocardial viscoelasticity in vivo. In this measurement, the phase velocity of the wave is determined for each frequency component. By comparing the dispersion of the phase velocity with the theoretical one of the Lamb wave (the plate flexural wave), which propagates along the viscoelastic plate (heart wall) immersed in blood, the instantaneous viscoelasticity is determined noninvasively. This is the first report of such noninvasive determination. In in vivo experiments applied to five healthy subjects, propagation of the pulsive wave was clearly visible in all subjects. For the 60-Hz component, the typical propagation speed rapidly decreased from 5 m/s just before the time of AVC (t = T0 - 8 ms) to 3 m/s at t = T0 + 10 ms. In the experiments, it was possible to determine the viscosity more precisely than the elasticity. The typical value of elasticity was about 24-30 kPa and did not change around the time of AVC. The typical transient values of viscosity decreased rapidly from 400 Pa x s at t = T0 - 8 ms to 70 Pa x s at t = T0 + 10 ms. The measured shear elasticity and viscosity in this study are comparable to those obtained for the human tissues using audio frequency in in vitro experiments reported in the literature.     

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.     

Shear elasticity probe for soft tissues with 1-D transient elastography

Important tissue parameters such as elasticity can be deduced from the study of the propagation of low frequency shear waves. A new method for measuring the shear velocity in soft tissues is presented in this paper. Unlike conventional transient elastography in which the ultrasonic transducer and the low frequency vibrator are two separated parts, the new method relies on a probe that associates the vibrator and the transducer, which is built on the axis of the vibrator. This setup is easy to use. The low frequency shear wave is driven by the transducer itself that acts as a piston while it is used in pulse echo mode to acquire ultrasonic lines. The results obtained with the new method are in good agreement with those obtained with the conventional one.     

Pulse wave imaging of the human carotid artery: an in vivo feasibility study

Noninvasive quantification of regional arterial stiffness, such as measurement of the pulse wave velocity (PWV), has been shown to be of high clinical importance. Pulse wave imaging (PWI) has been previously developed by our group to visualize the propagation of the pulse wave along the aorta and to estimate the regional PWV. The objective of this paper is to determine the feasibility of PWI in the human carotid artery in vivo. The left common carotid arteries of eight (n = 8) healthy volunteers (male, age 27 + 4 years old) were scanned in a long-axis view, with a 10-MHz linear-array transducer. The beam density of the scan was reduced to 16 beams within an imaging width of 38 mm. The frame rate of ultrasound imaging was therefore increased to 1127 Hz at an image depth of 25 mm. The RF ultrasound signals were then acquired at a sampling rate of 40 MHz and used to estimate the velocity of the arterial wall using a 1-D cross-correlationbased speckle tracking method. The sequence of the wall velocity images at different times depicts the propagation of the pulse wave in the carotid artery from the proximal to distal sides. The regional PWV was estimated from the spatiotemporal variation of the wall velocities and ranged from 4.0 to 5.2 m/s in eight (n = 8) normal subjects, in agreement with findings reported in the literature. PWI was thus proven feasible in the human carotid artery, and may be proven useful for detecting vascular disease through mapping the pulse wave and estimating the regional PWV in the carotid artery.     

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.     

Computer simulation of forward wave propagation in soft tissue

A method for simulating forward wavefront propagation in heterogeneous tissue is discussed. The intended application of this method is for the study of aberration produced when performing ultrasound imaging through a layer of soft tissue. A one-way wave equation that permits smooth variation in all acoustically important variables is derived. This equation also describes tissue exhibiting nonlinear elasticity and arbitrary frequency-dependent relaxation. A numerical solution to this equation is found by means of operator splitting and propagation along the spatial depth coordinate. The numerical solution is accurate when compared to analytical solutions for special cases, and when compared to numerical solutions of the full wave equation by other methods. The presented implementation provides a fast numerical method for studying the impact of aberration in medical ultrasound imaging through soft tissue--both on the transmitted beam and the nonlinearly generated harmonic beam.     

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.     

Imaging feedback of histotripsy treatments using ultrasound shear wave elastography

Histotripsy is a cavitation-based ultrasound therapy that mechanically fractionates soft solid tissues into fluid-like homogenates. This paper investigates the feasibility of imaging the tissue elasticity change during the histotripsy process as a tool to provide feedback for the treatments. The treatments were performed on agar tissue phantoms and ex vivo kidneys using 3-cycle ultrasound pulses delivered by a 750-kHz therapeutic array at peak negative/positive pressure of 17/108 MPa and a repetition rate of 50 Hz. Lesions with different degrees of damage were created with increasing numbers of therapy pulses from 0 to 2000 pulses per treatment location. The elasticity of the lesions was measured with ultrasound shear wave elastography, in which a quasi-planar shear wave was induced by acoustic radiation force generated by the therapeutic array, and tracked with ultrasound imaging at 3000 frames per second. Based on the shear wave velocity calculated from the sequentially captured frames, the Young's modulus was reconstructed. Results showed that the lesions were more easily identified on the shear wave velocity images than on B-mode images. As the number of therapy pulses increased from 0 to 2000 pulses/location, the Young's modulus decreased exponentially from 22.1 ± 2.7 to 2.1 ± 1.1 kPa in the tissue phantoms (R2 = 0.99, N = 9 each), and from 33.0 ± 7.1 to 4.0 ± 2.5 kPa in the ex vivo kidneys (R2 = 0.99, N = 8 each). Correspondingly, the tissues transformed from completely intact to completely fractionated as examined via histology. A good correlation existed between the lesions' Young's modulus and the degree of tissue fractionation as examined with the percentage of remaining structurally intact cell nuclei (R2 = 0.91, N = 8 each). These results indicate that lesions produced by histotripsy can be detected with high sensitivity using shear wave elastography. Because the decrease in the tissue elasticity corresponded well with the morphological and histological change, this study provides a basis for predicting the local treatment outcomes from tissue elasticity change.     

Nonlinear propagation of ultrasound through microbubble contrast agents and implications for imaging

Microbubble contrast agents produce nonlinear echoes under ultrasound insonation, and current imaging techniques detect these nonlinear echoes to generate contrast agent images accordingly. For these techniques, there is a potential problem in that bubbles along the ultrasound transmission path between transducer and target can alter the ultrasound transmission nonlinearly and contribute to the nonlinear echoes. This can lead to imaging artefacts, especially in regions at depth. In this paper we provide insight, through both simulation and experimental measurement, into the nonlinear propagation caused by microbubbles and the implications for current imaging techniques. A series of investigations at frequencies below, at, and above the resonance frequency of microbubbles were performed. Three specific effects on the pulse propagation (i.e., amplitude attenuation, phase changes, and harmonic generation) were studied. It was found that all these effects are dependent on the initial pulse amplitude, and their dependence on the initial phase of the pulse is shown to be insignificant. Two types of imaging errors are shown to result from this nonlinear propagation: first, that tissue can be misclassified as microbubbles; second, the concentration of microbubbles in the image can be misrepresented. It is found that these imaging errors are significant for all three pulse frequencies when the pulses transmit through a microbubble suspension of 6 cm in path length. It also is found that the first type of error is larger at the bubble resonance frequency.     

Position and time-delay calibration of transducer elements in a sparse array for underwater ultrasound imaging

This paper describes a novel method for the calibration of the position and time delay of transducer elements in a large, sparse array used for underwater, high-resolution ultrasound imaging. This method is based on the principles used in the global positioning system (GPS). However, unlike GPS, in which the wave propagation speed is generally assumed known, the sound propagation speed in the water usually is unknown and it is calibrated simultaneously in this method to achieve high calibration accuracy. In this method, a high-precision positioning system is used to scan a single hydrophone (used for transmission) in the imaging field of the array. The hydrophone transmits pulses at selected positions, and the transducer elements in the sparse array receive the transmitted signals. Time of flight (TOF) values between transducer elements and hydrophone positions then are measured. From a series of measured TOF values, the position and time delay values for each transducer element as well as the propagation speed can be calibrated. The performances of the calibration algorithm are theoretically analyzed and evaluated with numerical calculations and simulation studies. It is found that this method is capable of calibrating the positions and time delays of transducer elements with high accuracy.     

The role of numerical simulation for the development of an advanced HIFU system

High-intensity focused ultrasound (HIFU) has been used clinically and is under clinical trials to treat various diseases. An advanced HIFU system employs ultrasound techniques for guidance during HIFU treatment instead of magnetic resonance imaging in current HIFU systems. A HIFU beam imaging for monitoring the HIFU beam and a localized motion imaging for treatment validation of tissue are introduced briefly as the real-time ultrasound monitoring techniques. Numerical simulations have a great impact on the development of real-time ultrasound monitoring as well as the improvement of the safety and efficacy of treatment in advanced HIFU systems. A HIFU simulator was developed to reproduce ultrasound propagation through the body in consideration of the elasticity of tissue, and was validated by comparison with in vitro experiments in which the ultrasound emitted from the phased-array transducer propagates through the acrylic plate acting as a bone phantom. As the result, the defocus and distortion of the ultrasound propagating through the acrylic plate in the simulation quantitatively agree with that in the experimental results. Therefore, the HIFU simulator accurately reproduces the ultrasound propagation through the medium whose shape and physical properties are well known. In addition, it is experimentally confirmed that simulation-assisted focus control of the phased-array transducer enables efficient assignment of the focus to the target. Simulation-assisted focus control can contribute to design of transducers and treatment planning.     

Design of a multilayer transducer for acoustic bladder volume assessment

Catheterization remains the "gold standard" for bladder volume assessment, but it is invasive and introduces the risk of infections and traumas. Therefore, noninvasive bladder volume measurement methods have gained interest. In a preceding study a new technique to measure the bladder volume on the basis of nonlinear ultrasound wave propagation was validated. This paper describes a first prototype of a dedicated multilayer transducer to implement this approach. It is composed of a PZT transducer for transmission and a PVDF layer for reception. Acoustical measurements in a water tank and phantom measurements showed that there is a relation between bladder volume and the harmonic contents of the echo obtained from a region of interest behind the bladder. Simulations with an equivalent transducer model on the basis of KLM-circuit modeling closely matched with the results from the acoustical measurements. The results demonstrated the feasibility of the multilayer transducer design for bladder volume assessment on the basis of nonlinear wave propagation.     

Narrowband shear wave generation by a Finite-Amplitude radiation force: The fundamental component

A highly localized source of low-frequency shear waves can be created by the modulated radiation force resulting from two intersecting quasi-continuous-wave ultrasound beams of slightly different frequencies. In contrast to most other radiation force-based methods, these shear waves can be narrowband. Consequently, different frequency-dependent effects will not significantly affect their spectrum as they propagate within a viscoelastic medium, thereby enabling the viscoelastic shear properties of the medium to be determined at any given modulation frequency. This can be achieved by tracking the shear wave phase delay and change in amplitude over a specific distance. In this paper we explore the properties of short duration (dynamic) low-frequency shear wave propagation and study how the shear displacement field depends on the excitation conditions. Our investigations make use of the approximate Green's functions for viscoelastic media, and the evolution of such waves is studied in the spatiotemporal domain from a theoretical perspective. Although nonlinearities are included in our confocal source model, just the properties of the fundamental shear component are examined in this paper. We examine how the shear wave propagation is affected by the shear viscosity, the coupling wave, the spatial distribution of the force, the shear speed, and the duration of the modulated wave. A method is proposed for estimating the shear viscosity of a viscoelastic medium. In addition, it is shown how the Voigt model paremeters can be extracted from the frequency-dependent speed and attenuation.     

Phase aberration correction using ultrasound radiation force and vibrometry optimization

We describe a phase aberration correction method that uses dynamic ultrasound radiation force to harmonically vibrate an object using amplitude modulated continuous wave ultrasound. The phase of each element of an annular array transducer is adjusted to maximize the radiation force and obtain optimal focus of the ultrasound beam. The maximization of the radiation force is performed by monitoring the velocity of scatterers in the focus region. We present theory that shows focal optimization with radiation force has a well-behaved cost function. Experimental validation is shown by correction of manual defocusing of an annular array as well as correcting for a lens-shaped aberrator placed near the transducer. A Doppler laser vibrometer and a pulse-echo Doppler ultrasound method were used to monitor the velocity of a sphere used as a target for the transducer. By maximizing the radiation force-induced vibration of scatterers in the focal region, the resolution of the ultrasound beam can be recovered after aberration defocusing.     

Real-time angular scatter imaging system for improved tissuecontrast in diagnostic ultrasound images

A new type of real-time ultrasound imaging system has been developed. In contrast to conventional systems, which process only echoes scattered directly back from tissue to form an image, this system images tissue by displaying energy scattered at other angles. In its present form, the system uses one 32 element, 2.4 MHz phased array transducer in transmit and a second, spatially separate 32 element, 2.4 MHz phased array transducer in receive, to detect sound which is scattered away from the transmit transducer. In order to form an image line, the transmit transducer sends into the body a steered pulse, which is tracked dynamically from the side by the receive transducer. The signal detected by the receive transducer is processed in the same manner as in a standard B-mode phased array system. The final display format is a gray scale sector originating from the transmit transducer. Real-time angular scatter images of phantom and in vivo targets have been formed and compared to standard backscatter B-mode images of the same targets     

PSpice simulation of ultrasonic systems

The usage of electrical analogies for the simulation of wave generation and propagation in ultrasound transducers is well established. In this paper a PSpice approach that includes the temperature and frequency dependency of the transducer performance is proposed. The analogy between acoustic wave propagation and wave propagation in an electric transmission line is given. Further ways to deduce temperature and frequency dependencies are discussed. The simulation approach is applied to a pulse-echo setup for the determination of speed of sound and attenuation in liquids and solids. Experiments and simulations are made for three temperatures and in the frequency range 1-12 MHz using water, glycerine, and polymers (PMMA and PEEK) as test samples. Comparison shows a good agreement between simulation and experiments. Results for glycerine indicates that the available attenuation models for high viscosity liquids is inappropriate.     

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。     

Imaging in diffuse media with pulsed-ultrasound-modulated light and the photorefractive effect

Acousto-optic imaging in diffuse media is a dual wave-sensing technique in which an acoustic field interacts with multiply scattered laser light. The acoustic field causes a phase modulation in the optical field emanating from the interaction region, and this phase-modulated optical field carries with it information about the local optomechanical properties of the media. We report on the use of a pulsed ultrasound transducer to modulate the optical field and the use of a photorefractive-crystal-based interferometry system to detect ultrasound-modulated light. The use of short pulses of focused ultrasound allows for a one-dimensional acousto-optic image to be obtained along the transducer axis from a single, time-averaged acousto-optic signal. The axial and lateral resolutions of the system are controlled by the spatial pulse length and width of the ultrasound beam, respectively. In addition, scanning the ultrasound transducer in one dimension yields two-dimensional images of optical inhomogeneities buried in turbid media.