Kathryn R. Nightingale

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.

On the feasibility of remote palpation using acoustic radiation force.

A method of acoustic remote palpation, capable of imaging local variations in the mechanical properties of tissue, is under investigation. In this method, focused ultrasound is used to apply localized (on the order of 2 mm3) radiation force within tissue. 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. In this paper, the feasibility of remote palpation is demonstrated experimentally using breast tissue phantoms with spherical lesion inclusions, and in vitro liver samples. A single diagnostic transducer and modified ultrasonic imaging system are used to perform remote palpation. The displacement images are directly correlated to local variations in tissue stiffness with higher contrast than the corresponding B-mode images. Relationships between acoustic beam parameters, lesion characteristics and radiation force induced tissue displacement patterns are investigated and discussed. The results show promise for the clinical implementation of remote palpation.

Quantifying Hepatic Shear Modulus In Vivo Using Acoustic Radiation Force

The speed at which shear waves propagate in tissue can be used to quantify the shear modulus of the tissue. As many groups have shown, shear waves can be generated within tissues using focused, impulsive, acoustic radiation force excitations, and the resulting displacement response can be ultrasonically tracked through time. The goals of the work herein are twofold: (i) to develop and validate an algorithm to quantify shear wave speed from radiation force-induced, ultrasonically-detected displacement data that is robust in the presence of poor displacement signal-to-noise ratio and (ii) to apply this algorithm to in vivo datasets acquired in human volunteers to demonstrate the clinical feasibility of using this method to quantify the shear modulus of liver tissue in longitudinal studies. The ultimate clinical application of this work is noninvasive quantification of liver stiffness in the setting of fibrosis and steatosis. In the proposed algorithm, time-to-peak displacement data in response to impulsive acoustic radiation force outside the region of excitation are used to characterize the shear wave speed of a material, which is used to reconstruct the materials shear modulus. The algorithm is developed and validated using finite element method simulations. By using this algorithm on simulated displacement fields, reconstructions for materials with shear moduli (mu) ranging from 1.3-5 kPa are accurate to within 0.3 kPa, whereas stiffer shear moduli ranging from 10-16 kPa are accurate to within 1.0 kPa. Ultrasonically tracking the displacement data, which introduces jitter in the displacement estimates, does not impede the use of this algorithm to reconstruct accurate shear moduli. By using in vivo data acquired intercostally in 20 volunteers with body mass indices ranging from normal to obese, liver shear moduli have been reconstructed between 0.9 and 3.0 kPa, with an average precision of +/-0.4 kPa. These reconstructed liver moduli are consistent with those reported in the literature (mu = 0.75-2.5 kPa) with a similar precision (+/-0.3 kPa). Repeated intercostal liver shear modulus reconstructions were performed on nine different days in two volunteers over a 105-day period, yielding an average shear modulus of 1.9 +/- 0.50 kPa (1.3-2.5 kPa) in the first volunteer and 1.8 +/- 0.4 kPa (1.1-3.0 kPa) in the second volunteer. The simulation and in vivo data to date demonstrate that this method is capable of generating accurate and repeatable liver stiffness measurements and appears promising as a clinical tool for quantifying liver stiffness.

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening. METHODS Acoustic Radiation Force Impulse (ARFI) shear wave imaging, a noninvasive method of assessing tissue stiffness, was used to evaluate liver fibrosis in 172 patients diagnosed with NAFLD. Liver shear stiffness measures in three different imaging locations were reconstructed and compared to the histologic features of NAFLD and AST-to-platelet ratio indices (APRI). RESULTS Reconstructed shear stiffnesses were not associated with ballooned hepatocytes (p=0.11), inflammation (p=0.69), nor imaging location (p=0.11). Using a predictive shear stiffness threshold of 4.24kPa, shear stiffness distinguished low (fibrosis stage 0-2) from high (fibrosis stage 3-4) fibrosis stages with a sensitivity of 90% and a specificity of 90% (AUC of 0.90). Shear stiffness had a mild correlation with APRI (R(2)=0.22). BMI>40kg/m(2) was not a limiting factor for ARFI imaging, and no correlation was noted between BMI and shear stiffness (R(2)=0.05). CONCLUSIONS ARFI imaging is a promising imaging modality for assessing the presence or absence of advanced fibrosis in patients with obesity-related liver disease.

A finite-element method model of soft tissue response to impulsive acoustic radiation force

Several groups are studying acoustic radiation force and its ability to image the mechanical properties of tissue. Acoustic radiation force impulse (ARFI) imaging is one modality using standard diagnostic ultrasound scanners to generate localized, impulsive, acoustic radiation forces in tissue. The dynamic response of tissue is measured via conventional ultrasonic speckle-tracking methods and provides information about the mechanical properties of tissue. A finite-element method (FEM) model has been developed that simulates the dynamic response of tissues, with and without spherical inclusions, to an impulsive acoustic radiation force excitation from a linear array transducer. These FEM models were validated with calibrated phantoms. Shear wave speed, and therefore elasticity, dictates tissue relaxation following ARFI excitation, but Poissons ratio and density do not significantly alter tissue relaxation rates. Increased acoustic attenuation in tissue increases the relative amount of tissue displacement in the near field compared with the focal depth, but relaxation rates are not altered. Applications of this model include improving image quality, and distilling material and structural information from tissues dynamic response to ARFI excitation. Future work on these models includes incorporation of viscous material properties and modeling the ultrasonic tracking of displaced scatterers.

WFUMB Guidelines and Recommendations for Clinical Use of Ultrasound Elastography: Part 2: Breast

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced these guidelines for the use of elastography techniques in liver disease. For each available technique, the reproducibility, results, and limitations are analyzed, and recommendations are given. Finally, recommendations based on the international literature and the findings of the WFUMB expert group are established as answers to common questions. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.

A preliminary evaluation of the effects of primary and secondary radiation forces on acoustic contrast agents

Primary and secondary radiation forces result from pressure gradients in the incident and scattered ultrasonic fields. These forces and their dependence on experimental parameters are described, and the theory for primary radiation force is extended to consider a pulsed traveling wave. Both primary and secondary radiation forces are shown to have a significant effect on the flow of microbubbles through a small vessel during insonation. The primary radiation force produces displacement of microspheres across a 100 micron vessel radius for a small transmitted acoustic pressure. The displacement produced by primary radiation force is shown to display the expected linear dependence on the pulse repetition frequency and a nonlinear dependence on transmitted pressure. The secondary radiation force produces a reversible attraction and aggregation of microspheres with a significant attraction over a distance of approximately 100 microns. The magnitude of the secondary radiation force is proportional to the inverse of the squared separation distance, and thus two aggregates accelerate as they approach one another. We show that this force is sufficient to produce aggregates that remain intact for a physiologically appropriate shear rate. Brief interruption of acoustic transmission allows an immediate disruption of the aggregate.

Acoustic radiation force elasticity imaging in diagnostic ultrasound

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo; elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed noninvasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods.

Ultrasonic tracking of acoustic radiation force-induced displacements in homogeneous media

The use of ultrasonic methods to track the tissue deformation generated by acoustic radiation force is subject to jitter and displacement underestimation errors, with displacement underestimation being primarily caused by lateral and elevation shearing within the point spread function (PSF) of the ultrasonic beam. Models have been developed using finite element methods and Field II, a linear acoustic field simulation package, to study the impact of focal configuration, tracking frequency, and material properties on the accuracy of ultrasonically tracking the tissue deformation generated by acoustic radiation force excitations. These models demonstrate that lateral and elevation shearing underneath the PSF of the tracking beam leads to displacement underestimation in the focal zone. Displacement underestimation can be reduced by using tracking beams that are narrower than the spatial extent of the displacement fields. Displacement underestimation and jitter decrease with time after excitation as shear wave propagation away from the region of excitation reduces shearing in the lateral and elevation dimensions. The use of higher tracking frequencies in broadband transducers, along with 2D focusing in the elevation dimension, will reduce jitter and improve displacement tracking accuracy. Relative displacement underestimation remains constant as a function of applied force, whereas jitter increases with applied force. Underdeveloped speckle (SNR < 1.91) leads to greater levels of jitter and peak displacement underestimation. Axial shearing is minimal over the tracking kernel lengths used in acoustic radiation force impulse imaging and thus does not impact displacement tracking.

A parallel tracking method for acoustic radiation force impulse imaging

Radiation force-based techniques have been developed by several groups for imaging the mechanical properties of tissue. Acoustic radiation force impulse (ARFI) imaging is one such method that uses commercially available scanners to generate localized radiation forces in tissue. The response of the tissue to the radiation force is determined using conventional B-mode imaging pulses to track micron-scale displacements in tissue. Current research in ARFI imaging is focused on producing real-time images of tissue displacements arid related mechanical properties. Obstacles to producing a real-time ARFl imaging modality include data acquisition, processing power, data transfer rates, heating of the transducer, and patient safety concerns. We propose a parallel receive beamforming technique to reduce transducer heating and patient acoustic exposure, and to facilitate data acquisition for real-time ARFI imaging. Custom beam sequencing was used with a commercially available scanner to track tissue displacements with parallel-receive beamforming in tissue-mimicking phantoms. Using simulations, the effects of material properties on parallel tracking are observed. Transducer and tissue heating for parallel tracking are compared to standard ARFI beam sequencing. The effects of tracking beam position and size of the tracked region are also discussed in relation to the size and temporal response of the region of applied force, and the impact on ARFI image contrast arid signal-to-noise ratio are quantified