Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility

The clinical viability of a method of acoustic remote palpation, capable of imaging local variations in the mechanical properties of soft tissue using acoustic radiation force impulse (ARFI) imaging, is investigated in vivo. In this method, focused ultrasound (US) is used to apply localized radiation force to small volumes of tissue (2 mm(3)) for short durations (less than 1 ms) and the resulting tissue displacements are mapped using ultrasonic correlation-based methods. The tissue displacements are inversely proportional to the stiffness of the tissue and, thus, a stiffer region of tissue exhibits smaller displacements than a more compliant region. Due to the short duration of the force application, this method provides information about the mechanical impulse response of the tissue, which reflects variations in tissue viscoelastic characteristics. In this paper, experimental results are presented demonstrating that displacements on the order of 10 microm can be generated and detected in soft tissues in vivo using a single transducer on a modified diagnostic US scanner. Differences in the magnitude of displacement and the transient response of tissue are correlated with tissue structures in matched B-mode images. The results comprise the first in vivo ARFI images, and support the clinical feasibility of a radiation force-based remote palpation imaging system.     

Analysis of contrast in images generated with transient acoustic radiation force

Several mechanical imaging methods are under investigation that use focused ultrasound (US) as a source of mechanical excitation. Images are then generated of the tissue response to this localized excitation. One such method, acoustic radiation force impulse (ARFI) imaging, utilizes a single US transducer on a commercial US system to transmit brief, high-energy, focused acoustic pulses to generate radiation force in tissue and correlation-based US methods to detect the resulting tissue displacements. Local displacements reflect relative mechanical properties of tissue. The resolution of these images is comparable with that of conventional B-mode imaging. The response of tissue to focused radiation force excitation is complex and depends upon tissue geometry, forcing function geometry (i.e., region of excitation, or ROE) and tissue mechanical and acoustic properties. Finite element method (FEM) simulations using an experimentally validated model and phantom experiments have been performed using varying systems, system configurations and tissue-mimicking phantoms to determine their impact on image quality. Image quality is assessed by lesion contrast. Due to the dynamic nature of ARFI excitation, lesion contrast is temporally-dependent. Contrast of spherical inclusions is highest immediately after force cessation, decreases with time postforce and then reverses, due to shear wave interaction with internal boundaries, differences in shear modulus between lesions and background and inertial effects. In images generated immediately after force cessation, contrast does not vary with applied force, increases with lesion stiffness and increases as the ROE size decreases relative to the size of the structure being imaged. These studies indicate that improved contrast in radiation force-generated images will be achieved as ROE size decreases; however, frame rate and thermal considerations present trade-offs with small ROE size.     

Thermal Safety Simulations of Transient Temperature Rise during Acoustic Radiation Force-Based Ultrasound Elastography

Ultrasound transient elastography is a new diagnostic imaging technique that uses acoustic radiation force to produce motion in solid tissue via a high-intensity, long-duration “push” beam. In our previous work, we developed analytical models for calculating transient temperature rise, both in soft tissue and at a bone/soft tissue interface, during a single acoustic radiation force impulse (ARFI) imaging frame. The present study expands on these temperature rise calculations, providing applicable range assessment and error analysis for a single ARFI frame. Furthermore, a “virtual source” approach is described for temperature and thermal dose calculation under multiple ARFI frames. By use of this method, the effect of inter-frame cooling duration on temperature prediction is analyzed, and a thermal buildup phenomenon is revealed. Thermal safety assessment indicates that the thermal dose values, especially at the absorptive bone/soft tissue interface, could approach recommended dose thresholds if the cooling interval of multiple-frame ARFI elastography is too short.     

Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract

The evaluation of lesions in the gastrointestinal (GI) tract using ultrasound can suffer from poor contrast between healthy and diseased tissue. Acoustic Radiation Force Impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force and ultrasonic correlation-based methods to track the resulting tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) investigate the potential for ARFI imaging to provide improvements over conventional B-mode imaging of GI lesions and (2) demonstrate that ARFI imaging can be performed with an endocavity probe. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction, status-post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue layers (i.e., mucosal, muscularis and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of ex vivo colon and small bowel tumors portray interesting contrast and structure that are not as well defined in B-mode images. An endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 4 microm. These findings support the clinical feasibility of endocavity ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.     

Frame rate considerations for real-time abdominal acoustic radiation force impulse imaging

With the advent of real-time Acoustic Radiation Force Impulse (ARFI) imaging, elevated frame rates are both desirable and relevant from a clinical perspective. However, fundamental limitations on frame rates are imposed by thermal safety concerns related to incident radiation force pulses. Abdominal ARFI imaging utilizes a curvilinear scanning geometry that results in markedly different tissue heating patterns than those previously studied for linear arrays or mechanically-translated concave transducers. Finite Element Method (FEM) models were used to simulate these tissue heating patterns and to analyze the impact of tissue heating on frame rates available for abdominal ARFI imaging. A perfusion model was implemented to account for cooling effects due to blood flow and frame rate limitations were evaluated in the presence of normal, reduced and negligible tissue perfusions. Conventional ARFI acquisition techniques were also compared to ARFI imaging with parallel receive tracking in terms of thermal efficiency. Additionally, thermocouple measurements of transducer face temperature increases were acquired to assess the frame rate limitations imposed by cumulative heating of the imaging array. Frame rates sufficient for many abdominal imaging applications were found to be safely achievable utilizing available ARFI imaging techniques.     

磁共振声辐射力成像技术研究进展

磁共振声辐射力成像（MR-ARFI）将声辐射力与MRI技术相结合,作为一种新兴的高强度聚焦超声（HIFU）治疗监控技术,能够通过探测组织内的微小位移而间接反映组织弹性,具有安全、简便、无需其他激励装置等优点。本文对MR-ARFI的原理、相关序列及其在生物医学方面的应用进展进行综述。     

ARFI imaging for noninvasive material characterization of atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death in the United States, with 70% of CVD mortalities the result of sequelae of atherosclerosis. An urgent need for enhanced delineation of vulnerable plaques has catalyzed the development of novel atherosclerosis imaging strategies that use X-ray computed tomography, magnetic resonance and ultrasound modalities. As suggested by the pathophysiology of plaque development and progression to vulnerability, insight to the focal material, i.e., mechanical, properties of arterial walls and plaques may enhance atherosclerosis characterization. We present acoustic radiation force impulse (ARFI) ultrasound in application to mechanically characterizing a raised focal atherosclerotic plaque in an iliac artery extracted from a relevant pig model. ARFI results are correlated to matched immunohistochemistry, indicating elastin and collagen composition. In regions of degraded elastin, slower recovery rates from peak ARFI-induced displacements were observed. In regions of collagen deposition, lower ARFI-induced displacements were achieved. This work demonstrates ARFI for characterizing the material nature of an atherosclerotic plaque.     

Acoustic Radiation Force Impulse Imaging for Noninvasive Characterization of Carotid Artery Atherosclerotic Plaques: A Feasibility Study

Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A stiff cap was observed covering the large soft tissue region, with the cap thickness ranging from 0.7–1.3 mm. (E-mail: jeremy.dahl@duke.edu)     

Observations of tissue response to acoustic radiation force: opportunities for imaging

Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing local variations in tissue mechanical properties. In this method, a single ultrasonic transducer array is used to both apply temporally short localized radiation forces within tissue and to track the resulting displacements through time. In an ongoing study of the response of tissue to temporally short radiation force excitation, ARFI datasets have been obtained of ex vivo tissues under various focal configurations. The goal of this paper is to report observations of the response of tissue to radiation force and discuss the implications of these results in the construction of clinical imaging devices.     

Characterizing stiffness of human prostates using acoustic radiation force

Acoustic Radiation Force Impulse (ARFI) imaging has been previously reported to portray normal anatomic structures and pathologies in ex vivo human prostates with good contrast and resolution. These findings were based on comparison with histological slides and McNeal's zonal anatomy. In ARFI images, the central zone (CZ) appears darker (smaller displacement) than other anatomic zones and prostate cancer (PCa) is darker than normal tissue in the peripheral zone (PZ). Since displacement amplitudes in ARFI images are determined by both the underlying tissue stiffness and the amplitude of acoustic radiation force that varies with acoustic attenuation, one question that arises is how the relative displacements in prostate ARFI images are related to the underlying prostatic tissue stiffness. In linear, isotropic elastic materials and in tissues that are relatively uniform in acoustic attenuation (e.g., liver), relative displacement in ARFI images has been shown to be correlated with underlying tissue stiffness. However, the prostate is known to be heterogeneous. Variations in acoustic attenuation of prostatic structures could confound the interpretation of ARFI images due to the associated variations in the applied acoustic radiation force. Therefore, in this study, co-registered three-dimensional (3D) ARFI datasets and quantitative shear wave elasticity imaging (SWEI) datasets were acquired in freshly-excised human prostates to investigate the relationship between displacement amplitudes in ARFI prostate images and the matched reconstructed shear moduli. The lateral time-to-peak (LTTP) algorithm was applied to the SWEI data to compute the shear-wave speed and reconstruct the shear moduli. Five types of prostatic tissue (PZ, CZ, transition zone (TZ) and benign prostatic hyperplasia (BPH), PCa and atrophy) were identified, whose shear moduli were quantified to be 4.1 +/- 0.8 kPa, 9.9 +/- 0.9 kPa, 4.8 +/- 0.6 kPa, 10.0 +/- 1.0 kPa and 8.0 kPa, respectively. Linear regression was performed to compare ARFI displacement amplitudes and the inverse of the corresponding reconstructed shear moduli at multiple depths. The results indicate an inverse relation between ARFI displacement amplitude and reconstructed shear modulus at all depths. These findings support the conclusion that ARFI prostate images portray underlying tissue stiffness variations.     

In vivo assessment of myocardial stiffness with acoustic radiation force impulse imaging

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing variations in local stiffness within soft tissue. Recent advances in ARFI beam sequencing and parallel imaging have shortened acquisition times and lessened transducer heating to a point where ARFI acquisitions can be executed at high frame rates on commercially available diagnostic scanners. In vivo ARFI images were acquired with a linear array placed on an exposed canine heart. The electrocardiogram (ECG) was also recorded. When coregistered with the ECG, ARFI displacement images of the heart reflect the expected myocardial stiffness changes during the cardiac cycle. A radio-frequency ablation was performed on the epicardial surface of the left ventricular free wall, creating a small lesion that did not vary in stiffness during a heartbeat, though continued to move with the rest of the heart. ARFI images showed a hemispherical, stiffer region at the ablation site whose displacement magnitude and temporal variation through the cardiac cycle were less than the surrounding untreated myocardium. Sequences with radiation force pulse amplitudes set to zero were acquired to measure potential cardiac motion artifacts within the ARFI images. The results show promise for real-time cardiac ARFI imaging.     

An integrated indenter-ARFI imaging system for tissue stiffness quantification

The goal of this work is to develop and characterize an integrated indenter-ARFI (acoustic radiation force impulse) imaging system. This system is capable of acquiring matched datasets of ARFI images and stiffness profiles from ex vivo tissue samples, which will facilitate correlation of ARFI images of tissue samples with independently-characterized material properties. For large and homogeneous samples, the indenter can be used to measure the Young's moduli by using Boussinesq's solution for a load on the surface ofa semi-infinite isotropic elastic medium. Experiments and finite element method (FEM) models were designed to determine the maximum indentation depth and minimum sample size for accurate modulus reconstruction using this solution. Applying these findings, indentation measurements were performed on three calibrated commercial tissue-mimicking phantoms and the results were in good agreement with the calibrated stiffness. For heterogeneous tissue samples, indentation can be used independently to characterize relative stiffness variation across the sample surface, which can then be used to validate the stiffness variation in registered ARFI images. Tests were performed on heterogeneous phantoms and freshly-excised colon cancer specimens to detect the relative stiffness and lesion sizes using the combined system. Normalized displacement curves across the lesion surface were calculated and compared. Good agreement ofthe lesion profiles was observed between indentation and ARFI imaging.     

ARFI Imaging for Noninvasive Material Characterization of Atherosclerosis Part II: Toward In Vivo Characterization

Seventy percent of cardiovascular disease (CVD) deaths are attributed to atherosclerosis. Despite their clinical significance, nonstenotic atherosclerotic plaques are not effectively detected by conventional atherosclerosis imaging methods. Moreover, conventional imaging methods are insufficient for describing plaque composition, which is relevant to cardiovascular risk assessment. Atherosclerosis imaging technologies capable of improving plaque detection and stratifying cardiovascular risk are needed. Acoustic radiation force impulse (ARFI) ultrasound, a novel imaging method for noninvasively differentiating the mechanical properties of tissue, is demonstrated for in vivo detection of nonstenotic plaques and plaque material assessment in this pilot investigation. In vivo ARFI imaging was performed on four iliac arteries: (1) of a normocholesterolemic pig with no atherosclerosis as a control, (2) of a familial hypercholesterolemic pig with diffuse atherosclerosis, (3) of a normocholesterolemic pig fed a high-fat diet with early atherosclerotic plaques and (4) of a familial hypercholesterolemic pig with diffuse atherosclerosis and a small, minimally occlusive plaque. ARFI results were compared with spatially matched immunohistochemistry, showing correlations between elastin and collagen content and ARFI-derived peak displacement and recovery time parameters. Faster recoveries from ARFI-induced peak displacements and smaller peak displacements were observed in areas of higher elastin and collagen content. Importantly, spatial correlations between tissue content and ARFI results were consistent and observable in large and highly evolved as well as small plaques. ARFI imaging successfully distinguished nonstenotic plaques, while conventional B-mode ultrasound did not. This work validates the potential relevance of ARFI imaging as a noninvasive imaging technology for in vivo detection and material assessment of atherosclerotic plaques. (E-mail: russbehler@unc.edu)     

Acoustic Radiation Force Impulse Imaging of Human Prostates Ex Vivo

It has been challenging for clinicians using current imaging modalities to visualize internal structures and detect lesions inside human prostates. Lack of contrast among prostatic tissues and high false positive or negative detection rates of prostate lesions have limited the use of current imaging modalities in the diagnosis of prostate cancer. In this study, acoustic radiation force impulse (ARFI) imaging is introduced to visualize the anatomical and abnormal structures in freshly excised human prostates. A modified Siemens Antares ultrasound scanner (Siemens Medical Solutions USA Inc., Malvern, PA) and a Siemens VF10-5 linear array were used to acquire ARFI images. The transducer was attached to a three-dimensional (3-D) translation stage, which was programmed to automate volumetric data acquisition. A depth dependent gain (DDG) method was developed and applied to 3-D ARFI datasets to compensate for the displacement gradients associated with spatially varying radiation force magnitudes as a function of depth. Nine human prostate specimens were collected and imaged immediately after surgical excision. Prostate anatomical structures such as seminal vesicles, ejaculatory ducts, peripheral zone, central zone, transition zone and verumontanum were visualized with high spatial resolution and in good agreement with McNeal's zonal anatomy. The characteristic appearance of prostate pathologies, such as prostate cancerous lesions, benign prostatic hyperplasia, calcified tissues and atrophy were identified in ARFI images based upon correlation with the corresponding histologic slides. This study demonstrates that ARFI imaging can be used to visualize internal structures and detecting suspicious lesions in the prostate and appears promising for image guidance of prostate biopsy. (E-mail:liang.zhai@duke.edu)     

Elastography for breast cancer diagnosis using radiation force: system development and performance evaluation

The use of impulsive acoustic radiation force for strain imaging was investigated. A focused ultrasound transducer was used to apply localized radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions, and was seen to vary approximately linearly with Young's modulus of the material. The highly localized and transient strain that is produced may permit the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography because of greater independence from boundary conditions. For example, the characteristic, bi-directional, high strain artefacts attributable to stress concentration, often seen with static elastography at tissue-inclusion interfaces, do not appear using the transient radiation force strain imaging technique.     

Imaging of Thermal Effects during High-Intensity Ultrasound Treatment in Liver by Passive Elastography: A Preliminary Feasibility in Vitro Study

High-intensity focused ultrasound is a non-invasive modality for thermal ablation of tissues through locally increased temperature. Thermal lesions can be monitored by elastography, following the changes in the elastic properties of the tissue as reflected by the shear-wave velocity. Most studies on ultrasound elastography use shear waves created by acoustic radiation force. However, in the human body, the natural noise resulting from cardiac activity or arterial pulsatility can be used to characterize elasticity through noise-correlation techniques, in the method known as passive elastography. The objective of this study was to investigate the feasibility of monitoring high-intensity ultrasound treatments of liver tissue using passive elastography. Bovine livers were heated to 80°C using a high-intensity planar transducer and imaged with a high-frame-rate ultrasound imaging device. The dynamics of lesion formation are captured through tissue stiffening and lesion expansion.     

Dual-mode ultrasound transducer for image-guided interstitial thermal therapy

Deep-seated tumors can be treated by minimally invasive interstitial ultrasound thermal therapy. A miniature transducer emitting high-intensity acoustic waves is placed in contact with the targeted area to induce local thermal necrosis. Accurate positioning of the probe and treatment monitoring must be achieved for the technique to be effective. A piezocomposite technology was used for obtaining both high-quality imaging and effective treatment with the same transducer. Prototypes were designed and built to be compatible with an endoscopic approach for treating cholangiocarcinomas in the biliary ducts. The transducer had dimensions of 2.5 x 7.5 mm(2), it was cylindrically focused at 10 mm and it was operated at a center frequency of 11 MHz. Transducer efficiency was measured at 71%, and the impulse response corresponded to an axial resolution of 0.2 mm. In-vitro tests were conducted on samples of pig liver in which lesions up to 10 mm in depth were induced. B-mode images were obtained by mechanically rotating the transducer. Treatments were monitored in three ways: (i) classical M-mode images, (ii) images of local deformation of ultrasound lines during heating and (iii) comparison of the displacements induced in the tissue by radiation force, before and after treatments. The successful use of piezocomposite materials to manufacture dual-mode transducers opens new perspectives for interstitial ultrasound thermal therapy.     

Acoustic radiation force impulse imaging of the abdomen: demonstration of feasibility and utility

The feasibility of utilizing acoustic radiation force impulse (ARFI) imaging to assess the mechanical properties of abdominal tissues was investigated. The thermal safety of the technique was also evaluated through the use of finite element method models. ARFI imaging was shown to be capable of imaging abdominal tissues at clinically realistic depths. Correspondence between anatomical structures in B-mode and ARFI images was observed. ARFI images showed similar tumor contrast when compared with B-mode images of ex vivo abdominal cancers. Finite element method models and in vitro measurements confirmed the thermal safety of ARFI imaging at depth. ARFI imaging is inexpensive, safe and convenient and is a promising modality for use in abdominal imaging.     

Shear-wave generation using acoustic radiation force: in vivo and ex vivo results

Acoustic radiation force impulse (ARFI) imaging involves the mechanical excitation of tissue using localized, impulsive radiation force. This results in shear-wave propagation away from the region of excitation. Using a single diagnostic transducer on a modified commercial ultrasound (US) scanner with conventional beam-forming architecture, repeated excitations with multiple look directions facilitate imaging shear-wave propagation. Direct inversion methods are then applied to estimate the associated Young's modulus. Shear-wave images are generated in tissue-mimicking phantoms, ex vivo human breast tissue and in vivo in the human abdomen. Mean Young's modulus values of between 3.8 and 5.6 kPa, 11.7 kPa and 14.0 kPa were estimated for fat, fibroadenoma and skin, respectively. Reasonable agreement is demonstrated between structures in matched B-mode and reconstructed modulus images. Although the relatively small magnitude of the displacement data presents some challenges, the reconstructions suggest the clinical feasibility of radiation force induced shear-wave imaging. (E-mail: kathy.nightingale@duke.edu)     

Acoustic radiation force impulse imaging of in vivo vastus medialis muscle under varying isometric load

Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing local variations in tissue mechanical properties. In this method, a single ultrasonic transducer array is used to both apply temporally short localized radiation forces within tissue and to track the resulting displacements through time. Images of tissue displacement immediately after force cessation, maximum tissue displacement, the time it takes for the tissue to reach its maximum displacement, and the recovery time constant of the tissue are generated from the ARFI data sets. The information in each of these images demonstrates good agreement with matched B-mode images. The study presented here was designed to evaluate the relationship between changes in these ARFI parameters with known tissue mechanical properties in vivo. Utilizing a modified Siemens Elegra scanner with a 75L40 transducer array, ARFI images of vastus medialis muscle were generated in three of the authors under four levels of activation (0, 5.7, 14.5, and 23.3 N-m). Four ARFI datasets were acquired for each loading condition. The observed trends were that displacement magnitude, the time it took for the tissue to reach its maximum displacement, and recovery time constant decreased with increasing load (i.e., increasing muscle stiffness). Significant differences were observed between load levels and subjects for all parameters (p<0.01). The results indicate that ARFI imaging may be capable of quantifying tissue stiffness in real-time measurements, although further investigation is required.