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.     

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.     

Supersonic shear imaging: a new technique for soft tissue elasticity mapping

Supersonic shear imaging (SSI) is a new ultrasound-based technique for real-time visualization of soft tissue viscoelastic properties. Using ultrasonic focused beams, it is possible to remotely generate mechanical vibration sources radiating low-frequency, shear waves inside tissues. Relying on this concept, SSI proposes to create such a source and make it move at a supersonic speed. In analogy with the "sonic boom" created by a supersonic aircraft, the resulting shear waves will interfere constructively along a Mach cone, creating two intense plane shear waves. These waves propagate through the medium and are progressively distorted by tissue heterogeneities. An ultrafast scanner prototype is able to both generate this supersonic source and image (5000 frames/s) the propagation of the resulting shear waves. Using inversion algorithms, the shear elasticity of medium can be mapped quantitatively from this propagation movie. The SSI enables tissue elasticity mapping in less than 20 ms, even in strongly viscous medium like breast. Modalities such as shear compounding are implementable by tilting shear waves in different directions and improving the elasticity estimation. Results validating SSI in heterogeneous phantoms are presented. The first in vivo investigations made on healthy volunteers emphasize the potential clinical applicability of SSI for breast cancer detection.     

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.     

Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT

In the last decade, high intensity focused ultrasound (HIFU) has gained popularity as a minimally invasive and noninvasive therapeutic tool for treatment of cancers, arrhythmias, and other medical conditions. HIFU therapy is often guided by magnetic resonance imaging (MRI), which provides anatomical images for therapeutic device placement, temperature maps for treatment guidance, and postoperative evaluation of the region of interest. While piezoelectric transducers are dominantly used for MR-guided HIFU, capacitive micromachined ultrasonic transducers (CMUTs) show competitive advantages, such as ease of fabrication, integration with electronics, improved efficiency, and reduction of self-heating. In this paper, we will show our first results of an unfocused CMUT transducer monitored by MR-temperature maps. This 2.51 mm by 2.32 mm, unfocused CMUT heated a HIFU phantom by 14 degrees C in 2.5 min. This temperature rise was successfully monitored by MR thermometry in a 3.0 T General Electric scanner.     

Assessment of shear modulus of tissue using ultrasound radiation force acting on a spherical acoustic inhomogeneity

An ultrasound-based method to locally assess the shear modulus of a medium is reported. The proposed approach is based on the application of an impulse acoustic radiation force to an inhomogeneity in the medium and subsequent monitoring of the spatio-temporal response. In our experimental studies, a short pulse produced by a 1.5-MHz highly focused ultrasound transducer was used to initiate the motion of a rigid sphere embedded into an elastic medium. Another 25 MHz focused ultrasound transducer operating in pulse-echo mode was used to track the displacement of the sphere. The experiments were performed in gel phantoms with varying shear modulus to demonstrate the relationship between the displacement of the sphere and shear modulus of the surrounding medium. Because the magnitude of acoustic force applied to sphere depends on the acoustic material properties and, therefore, cannot be used to assess the absolute value of shear modulus, the temporal behavior of the displacement of the sphere was analyzed. The results of this study indicate that there is a strong correlation between the shear modulus of a medium and spatio-temporal characteristics of the motion of the rigid sphere embedded in this medium.     

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.     

Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity

Characterization of tissue elasticity (stiffness) and viscosity has important medical applications because these properties are closely related to pathological changes. Quantitative measurement is more suitable than qualitative measurement (i.e., mapping with a relative scale) of tissue viscoelasticity for diagnosis of diffuse diseases where abnormality is not confined to a local region and there is no normal background tissue to provide contrast. Shearwave dispersion ultrasound vibrometry (SDUV) uses shear wave propagation speed measured in tissue at multiple frequencies (typically in the range of hundreds of Hertz) to solve quantitatively for both tissue elasticity and viscosity. A shear wave is stimulated within the tissue by an ultrasound push beam and monitored by a separate ultrasound detect beam. The phase difference of the shear wave between 2 locations along its propagation path is used to calculate shear wave speed within the tissue. In vitro SDUV measurements along and across bovine striated muscle fibers show results of tissue elasticity and viscosity close to literature values. An intermittent pulse sequence is developed to allow one array transducer for both push and detect function. Feasibility of this pulse sequence is demonstrated by in vivo SDUV measurements in swine liver using a dual transducer prototype simulating the operation of a single array transducer.     

The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force

Several ultrasound-based techniques for the estimation of soft tissue elasticity are currently being investigated. Most of them study the medium response to dynamic excitations. Such responses are usually modeled in a purely elastic medium using a Green's function solution of the motion equation. However, elasticity by itself is not necessarily a discriminant parameter for malignancy diagnosis. Modeling viscous properties of tissues could also be of great interest for tumor characterization. We report in this paper an explicit derivation of the Green's function in a viscous and elastic medium taking into account shear, bulk, and coupling waves. From this theoretical calculation, 3D simulations of mechanical waves in viscoelastic soft tissues are presented. The relevance of the viscoelastic Green's function is validated by comparing simulations with experimental data. The experiments were conducted using the supersonic shear imaging (SSI) technique which dynamically and remotely excites tissues using acoustic radiation force. We show that transient shear waves generated with SSI are modeled very precisely by the Green's function formalism. The combined influences of out-of-plane diffraction, beam shape, and shear viscosity on the shape of transient waves are carefully studied as they represent a major issue in ultrasound-based viscoelasticity 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.     

Temperature estimation using ultrasonic spatial compound imaging

The feasibility of temperature estimation during high-intensity focused ultrasound therapy using pulse-echo diagnostic ultrasound data has been demonstrated. This method is based upon the measurement of thermally-induced modifications in backscattered RF echoes due to thermal expansion and local changes in the speed of sound. It has been shown that strong ripple artifacts due to the thermo-acoustic lens effect severely corrupt the temperature estimates behind the heated region. We propose here a new imaging technique that improves the temperature estimation behind the heated region and reduces the variance of the temperature estimates in the entire image. We replaced the conventional beamforming on transmit with multiple steered plane wave insonifications using several subapertures. A two-dimensional temperature map is estimated from axial displacement maps between consecutive RF images of identically steered plane wave insonifications. Temperature estimation is then improved by averaging the two-dimensional maps from the multiple steered plane wave insonifications. Experiments were conducted in a tissue-mimicking gelatin-based phantom and in fresh bovine liver.     

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.     

A method to synchronize high-intensity, focused ultrasound with an arbitrary ultrasound imager

Ultrasound imaging is useful for monitoring high-intensity, focused ultrasound (HIFU) therapy; however, interference on the ultrasound image, caused by HIFU excitation, must be avoided. A method to synchronize HIFU excitation with ultrasound imaging is described here. Synchronization was tested with two unmodified, commercial imagers and two tissue phantoms.     

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.     

Noninvasive thermometry assisted by a dual-function ultrasound transducer for mild hyperthermia

Mild hyperthermia is increasingly important for the activation of temperature-sensitive drug delivery vehicles. Noninvasive ultrasound thermometry based on a 2-D speckle tracking algorithm was examined in this study. Here, a commercial ultrasound scanner, a customized co-linear array transducer, and a controlling PC system were used to generate mild hyperthermia. Because the co-linear array transducer is capable of both therapy and imaging at widely separated frequencies, RF image frames were acquired during therapeutic insonation and then exported for off-line analysis. For in vivo studies in a mouse model, before temperature estimation, motion correction was applied between a reference RF frame and subsequent RF frames. Both in vitro and in vivo experiments were examined; in the in vitro and in vivo studies, the average temperature error had a standard deviation of 0.7°C and 0.8°C, respectively. The application of motion correction improved the accuracy of temperature estimation, where the error range was 1.9 to 4.5°C without correction compared with 1.1 to 1.0°C following correction. This study demonstrates the feasibility of combining therapy and monitoring using a commercial system. In the future, real-time temperature estimation will be incorporated into this system.     

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.     

Single-element ultrasound transducer for combined vessel localization and ablation

This report describes a system that utilizes a single high-intensity focused ultrasound (HIFU) transducer for both the localization and ablation of arteries with internal diameters of 0.5 and 1.3 mm. In vitro and in vivo tests were performed to demonstrate both the imaging and ablation functionalities of this system. For imaging mode, pulsed acoustic waves (3 cycles for in vitro and 10 cycles for in vivo tests, 2 MPa peak pressure) were emitted from the 2-MHz HIFU transducer, and the backscattered ultrasonic signal was collected by the same transducer to calculate Doppler shifts in the target region. The maximum signal amplitude of the Doppler shift was used to determine the location of the target vessel. The operation mode was then switched to the therapeutic mode and vessel occlusion was successfully produced by high-intensity continuous HIFU waves (12 MPa) for 60 s. The system was then switched back to imaging mode for residual flow to determine the need for a second ablation treatment. The new system might be used to target and occlude unwanted vessels such as vasculature around tumors, and to help with tumor destruction.     

Elasticity imaging using conventional and high-frame rate ultrasound imaging: experimental study

High-frame rate ultrasound imaging is necessary to track fast deformation in ultrasound elasticity imaging, but the image quality may be degraded. Previously, we investigated the performance of strain imaging using numerical models of conventional and ultrafast ultrasound imaging techniques. In this paper, we performed experimental studies to quantitatively evaluate the strain images and elasticity maps obtained using conventional and high frame rate ultrasound imaging methods. The experiments were carried out using point target and tissue mimicking phantoms. The experimental results were compared with the results of numerical simulation. Our experimental studies confirm that the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and axial/lateral resolution of the displacement and strain images acquired using high-frame rate ultrasound imaging are slightly lower but comparable with those obtained using conventional imaging. Furthermore, the quality of elasticity images also exhibits similar trends. Thus, high-frame rate ultrasound imaging can be used reliably for static elasticity imaging to capture the internal tissue motion if the frame rate is critical.     

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from Bmode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimetersized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.     

Transverse shear modulus of SILICOMB cellular structures

This work describes the transverse shear stiffness properties of a novel honeycomb with zero Poisson’s ratio. The cellular configuration is simulated using a series of finite element models representing full-scale and representative unit cells of the honeycomb topology. The models are benchmarked against experimental results from pure shear and 3-point bending ASTM tests. The benchmarked models are used to perform a parametric study of the shear moduli (G₁₃ and G₂₃) against the geometry of the unit cell and the gauge thickness of the honeycomb panels. The shear stiffness maps obtained allow comparison of the SILICOMB configuration against classical centresymmetric and rectangular honeycomb topologies.