Joshua R. Doherty

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.

Acoustic radiation force impulse imaging of vulnerable plaques: a finite element method parametric analysis

Plaque rupture is the most common cause of complications such as stroke and coronary heart failure. Recent histopathological evidence suggests that several plaque features, including a large lipid core and a thin fibrous cap, are associated with plaques most at risk for rupture. Acoustic Radiation Force Impulse (ARFI) imaging, a recently developed ultrasound-based elasticity imaging technique, shows promise for imaging these features noninvasively. Clinically, this could be used to distinguish vulnerable plaques, for which surgical intervention may be required, from those less prone to rupture. In this study, a parametric analysis using Finite Element Method (FEM) models was performed to simulate ARFI imaging of five different carotid artery plaques across a wide range of material properties. It was demonstrated that ARFI imaging could resolve the softer lipid pool from the surrounding, stiffer media and fibrous cap and was most dependent upon the stiffness of the lipid pool component. Stress concentrations due to an ARFI excitation were located in the media and fibrous cap components. In all cases, the maximum Von Mises stress was<1.2 kPa. In comparing these results with others investigating plaque rupture, it is concluded that while the mechanisms may be different, the Von Mises stresses imposed by ARFI imaging are orders of magnitude lower than the stresses associated with blood pressure.

Harmonic tracking of acoustic radiation force-induced displacements

Ultrasound-based elasticity imaging methods rely upon accurate estimates of tissue deformation to characterize the mechanical properties of soft tissues. These methods are corrupted by clutter, which can bias and/or increase variance in displacement estimates. Harmonic imaging methods are routinely used for clutter suppression and improved image quality in conventional B-mode ultrasound, but have not been utilized in ultrasound-based elasticity imaging methods. We introduce a novel, fully-sampled pulse-inversion harmonic method for tracking tissue displacements that corrects the loss in temporal sampling frequency associated with conventional pulse-inversion techniques. The method is implemented with acoustic radiation force impulse (ARFI) imaging to monitor the displacements induced by an impulsive acoustic radiation force excitation. Custom pulse sequences were implemented on a diagnostic ultrasound scanner to collect spatially-matched fundamental and harmonic information within a single acquisition. B-mode and ARFI images created from fundamental data collected at 4 MHz and 8 MHz are compared with 8-MHz harmonic images created using a band-pass filter approach and the fully sampled pulse-inversion method. In homogeneous, tissue-mimicking phantoms, where no visible clutter was observed, there was little difference in the axial displacements, estimated jitter, and normalized cross-correlation among the fundamental and harmonic tracking methods. The similarity of the lowerand higher-frequency methods suggests that any improvement resulting from the increased frequency of the harmonic components is negligible. The harmonic tracking methods demonstrated a marked improvement in B-mode and ARFI image quality of in vivo carotid arteries. Improved feature detection and decreased variance in estimated displacements were observed in the arterial walls of harmonic ARFI images, especially in the pulse-inversion harmonic ARFI images. Within the lumen, the harmonic tracking methods improved the discrimination of the blood-vessel interface, making it easier to visualize plaque boundaries. Improvements in harmonic ARFI images in vivo were consistent with suppressed clutter supported by improved contrast and contrast-to-noise ratio (CNR) in the matched harmonic B-mode images compared with the fundamental B-mode images. These results suggest that harmonic tracking methods can improve the clinical utility and diagnostic accuracy of ultrasound-based elasticity imaging methods.

Comparison of Acoustic Radiation Force Impulse Imaging Derived Carotid Plaque Stiffness With Spatially Registered MRI Determined Composition

Measurements of plaque stiffness may provide important prognostic and diagnostic information to help clinicians distinguish vulnerable plaques containing soft lipid pools from more stable, stiffer plaques. In this preliminary study, we compare in vivo ultrasonic Acoustic Radiation Force Impulse (ARFI) imaging derived measures of carotid plaque stiffness with composition determined by spatially registered Magnetic Resonance Imaging (MRI) in five human subjects with stenosis >50%. Ultrasound imaging was implemented on a commercial diagnostic scanner with custom pulse sequences to collect spatially registered 2D longitudinal B-mode and ARFI images. A standardized, multi-contrast weighted MRI sequence was used to obtain 3D Time of Flight (TOF), T1 weighted (T1W), T2 weighted (T2W), and Proton Density Weighted (PDW) transverse image stacks of volumetric data. The MRI data was segmented to identify lipid, calcium, and normal loose matrix components using commercially available software. 3D MRI segmented plaque models were rendered and spatially registered with 2D B-mode images to create fused ultrasound and MRI volumetric images for each subject. ARFI imaging displacements in regions of interest (ROIs) derived from MRI segmented contours of varying composition were compared. Regions of calcium and normal loose matrix components identified by MRI presented as homogeneously stiff regions of similarly low (typically ≈ 1 μm) displacement in ARFI imaging. MRI identified lipid pools > 2 mm2, found in three out of five subjects, presented as softer regions of increased displacement that were on average 1.8 times greater than the displacements in adjacent regions of loose matrix components in spatially registered ARFI images. This work provides early evidence supporting the use of ARFI imaging to noninvasively identify lipid regions in carotid artery plaques in vivo that are believed to increase the propensity of a plaque to rupture. Additionally, the results provide early training data for future studies and aid in the interpretation and possible clinical utility of ARFI imaging for identifying the elusive vulnerable plaque.

Noninvasive Assessment of Wall-Shear Rate and Vascular Elasticity Using Combined ARFI/SWEI/Spectral Doppler Imaging System

The progression of atherosclerotic disease is a complex process believed to be a function of the localized mechanical properties and hemodynamic loading associated with the arterial wall. It is hypothesized that measurements of cardiovascular stiffness and wall-shear rate (WSR) may provide important information regarding vascular remodeling, endothelial function and the growth of soft lipid-filled plaques that could help a clinician better predict the occurrence of clinical events such as stroke. Two novel ARFI based imaging techniques, combined on-axis/off-axis ARFI/Spectral Doppler Imaging (SAD-SWEI) and Gated 2D ARFI/Spectral Doppler Imaging (SAD-Gated), were developed to form co-registered depictions of B-mode echogenicity, ARFI displacements, ARF-excited transverse wave velocity estimates and estimates of wall-shear rate throughout the cardiac cycle. Implemented on a commercial ultrasound scanner, the developed techniques were evaluated in tissue-mimicking and steady-state flow phantoms and compared with conventional techniques, other published study results and theoretical values. Initial in vivo feasibility of the method is demonstrated with results obtained from scanning the carotid arteries of five healthy volunteers. Cyclic variations over the cardiac cycle were observed in on-axis displacements, off-axis transverse-wave velocities and wall-shear rates.

Preliminary Results on the Feasibility of Using ARFI/SWEI to Assess Cutaneous Sclerotic Diseases.

In this study, acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) were applied to the skin to investigate the feasibility of their use in assessing sclerotic skin diseases. Our motivation was to develop a non-invasive imaging technology with real-time feedback of sclerotic skin disease diagnosis. This paper shows representative results from an ongoing study, recruiting patients with and without sclerosis. The stiffness of the imaged site was evaluated using two metrics: mean ARFI displacement magnitude and bulk shear wave speed inside the region of interest (ROI). In a subject with localized graft versus host disease (GVHD), the mean ARFI displacement inside sclerotic skin was 61% lower (p < 0.01) and shear wave speed 128% higher (p < 0.005) compared to those in normal skin-indicating stiffer mechanical properties in the sclerotic skin. This trend persisted through disease types. We conclude ARFI and SWEI can successfully differentiate sclerotic lesions from normal dermis.

Acoustic Radiation Force Impulse Imaging (ARFI) on an IVUS Circular Array

Our long-term goal is the detection and characterization of vulnerable plaque in the coronary arteries of the heart using intravascular ultrasound (IVUS) catheters. Vulnerable plaque, characterized by a thin fibrous cap and a soft, lipid-rich necrotic core is a precursor to heart attack and stroke. Early detection of such plaques may potentially alter the course of treatment of the patient to prevent ischemic events. We have previously described the characterization of carotid plaques using external linear arrays operating at 9 MHz. In addition, we previously modified circular array IVUS catheters by short-circuiting several neighboring elements to produce fixed beamwidths for intravascular hyperthermia applications. In this paper, we modified Volcano Visions 8.2 French, 9 MHz catheters and Volcano Platinum 3.5 French, 20 MHz catheters by short-circuiting portions of the array for acoustic radiation force impulse imaging (ARFI) applications. The catheters had an effective transmit aperture size of 2 mm and 1.5 mm, respectively. The catheters were connected to a Verasonics scanner and driven with pushing pulses of 180 V p-p to acquire ARFI data from a soft gel phantom with a Young’s modulus of 2.9 kPa. The dynamic response of the tissue-mimicking material demonstrates a typical ARFI motion of 1 to 2 microns as the gel phantom displaces away and recovers back to its normal position. The hardware modifications applied to our IVUS catheters mimic potential beamforming modifications that could be implemented on IVUS scanners. Our results demonstrate that the generation of radiation force from IVUS catheters and the development of intravascular ARFI may be feasible.

A harmonic tracking method for Acoustic Radiation Force Impulse (ARFI) imaging

Ultrasound-based elasticity imaging methods, such as Acoustic Radiation Force Impulse (ARFI) imaging, rely upon the accurate estimation of displacements to characterize the mechanical response of soft tissues. Sources of clutter, such as off-axis scattering and reverberation, can corrupt displacement estimates and result in noisy images. In this work, we investigated the use of filter-based and pulse inversion harmonic tracking methods to monitor the displacements induced by an ARFI excitation. A fully sampled method was developed that improves the temporal sampling frequency associated with the pulse inversion technique. Implemented on a conventional scanner, the harmonic tracking methods are compared with conventional ARFI imaging techniques that use the fundamental component of the received beam in phantoms and in vivo. In phantoms, where the generated harmonics are minimal, the harmonic and fundamental methods provided similar results. Decreased jitter and improved feature detection in ARFI images were obtained with harmonic tracking methods in vivo.

Development and evaluation of pulse sequences for freehand ARFI imaging

Acoustic Radiation Force Impulse (ARFI) imaging techniques can be used to non-invasively evaluate the relative stiffness of tissue; potentially aiding in the identification of stiff cancerous lesions or vulnerable soft lipid filled plaques in vasculature. In this work, we developed several pulse sequences that implement conventional B-mode interleaved with ARFI imaging for various frame rates and scan durations (ranging from 20 fps for 1 sec to 1 fps for 90 seconds). On-axis displacement estimates were calculated using a GPU processor for faster computation times. The clinical feasibility of the proposed pulse sequences was evaluated on the basis of transducer face heating, ISPTA, MI, and the observed spatial and temporal consistency of images acquired in vivo. Transducer face heating was <;2°C and FDA acoustic exposure limits were not exceeded. In phantoms, image degradation during a freehand swept scan is shown to be dependent upon the sonographer. In vivo multi-frame movie sequences showed consistent measurements of on-axis displacements across multiple frames and acquisitions. Overall data acquisition, processing, and display frame rates of 1.0 Hz were achieved, allowing for low frame rate sequences to provide feedback information during the swept scan.

Acoustic radiation force impulse imaging on an IVUS circular array

Our long-term goal is the detection and characterization of vulnerable plaque in the coronary arteries of the heart using IVUS catheters. Vulnerable plaque, characterized by a thin fibrous cap and a soft, lipid-rich, necrotic core is a pre-cursor to heart attack and stroke. Early detection of such plaques may potentially alter the course of treatment of the patient in order to prevent ischemic events. In this paper, we modified Volcano Visions 8.2 French, 9MHz catheters and Volcano Platinum 3.5 French, 20MHz catheters by short circuiting portions of the array for ARFI applications. The catheters had an effective transmit aperture size of 2mm and 1.5mm respectively. The catheters were connected to a Verasonics scanner and driven with pushing pulses of 180Vp-p to acquire ARFI data from a soft gel phantom with a Youngs modulus of 2.9 kPa. The dynamic response of the tissue-mimicking material demonstrates a typical ARFI motion of 1-2 microns as the gel phantom displaces away and recovers back to its normal position. Our results demonstrate that the generation of radiation force from IVUS catheters and the development of intravascular ARFI may be feasible.