Viscoelastic response (VisR) imaging for assessment of viscoelasticity in voigt materials

Viscoelastic response (VisR) imaging is presented as a new acoustic radiation force (ARF)-based elastographic imaging method. Exploiting the Voigt model, VisR imaging estimates displacement in only the ARF region of excitation from one or two successive ARF impulses to estimate τσ, the relaxation time for constant stress. Double-push VisR τσ estimates were not statistically significantly different (p < 0.02) from those of shearwave dispersion ultrasound vibrometry (SDUV) or monitored steady-state excitation recovery (MSSER) ultrasound in six homogeneous viscoelastic tissue mimicking phantoms with elastic moduli ranging from 3.92 to 15.34 kPa and coefficients of viscosity ranging from 0.87 to 14.06 Pa·s. In two-dimensional imaging, double-push VisR τσ images discriminated a viscous spherical inclusion in a structured phantom with higher CNR over a larger axial range than single-push VisR or conventional acoustic radiation force impulse (ARFI) ultrasound. Finally, 2-D in vivo double-push VisR images in normal canine semitendinosus muscle were compared with spatially matched histochemistry to corroborate lower double-push VisR τσ values in highly collagenated connective tissue than in muscle, suggesting double-push VisR’s in vivo relevance to diagnostic imaging, particularly in muscle. The key advantages and disadvantages to VisR, including lack of compensation for inertial terms, are discussed

Experimental Validation of Displacement Underestimation in ARFI Ultrasound

Acoustic radiation force impulse (ARFI) imaging is an elastography technique that uses ultrasonic pulses to both displace and track tissue motion. Previous modeling studies have shown that ARFI displacements are susceptible to underestimation due to lateral and elevational shearing that occurs within the tracking resolution cell. In this study, optical tracking was utilized to experimentally measure the displacement underestimation achieved by acoustic tracking using a clinical ultrasound system. Three optically translucent phantoms of varying stiffness were created, embedded with sub-wavelength diameter microspheres, and ARFI excitation pulses with F/1.5 or F/3 lateral focal configurations were transmitted from a standard linear array to induce phantom motion. Displacements were tracked using confocal optical and acoustic methods. As predicted by earlier FEM studies, significant acoustic displacement underestimation was observed for both excitation focal configurations; the maximum underestimation error was 35% of the optically measured displacement for the F/1.5 excitation pulse in the softest phantom. Using higher F/#, less tightly focused beams in the lateral dimension improved accuracy of displacements by approximately 10 percentage points. This work experimentally demonstrates limitations of ARFI implemented on a clinical scanner using a standard linear array and sets up a framework for future displacement tracking validation studies

ARFI Ultrasound for In Vivo Hemostasis Assessment Postcardiac Catheterization, Part I: Preclinical Studies

In this second of a two part series, we present pilot clinical data demonstrating Acoustic Radiation Force Impulse (ARFI) ultrasound for monitoring the onset of subcutaneous hemostasis at femoral artery puncture sites (arteriotomies), in vivo. We conducted a randomized, reader-blinded investigation of 20 patient volunteers who underwent diagnostic percutaneous coronary catheterization. After sheath removal (6 French), patients were randomized to treatment with either standard of care manual compression alone or, to expedite hemostasis, manual compression augmented with a p-GlcNAc fiber-based hemostatic dressing (Marine Polymer Technologies, Danvers MA). Concurrent with manual compression, serial ARFI imaging began at the time of sheath removal and continued every minute for 15 min. Serial data sets were processed with custom software to (1) estimate the time of hemostasis onset, and (2) render hybrid ARFI/B-Mode images to highlight displacements considered to correspond to extravasted blood. Images were read by an observer blinded to the treatment groups. Average estimated times to hemostasis in patient volunteers treated with manual compression alone (n = 10) and manual compression augmented by hemostatic dressing (n = 9) were, respectively, 13.00 ± 1.56 and 9.44 ± 3.09 min, which are statistically significantly different (p = 0.0065, Wilcoxon two-sample test). Example images are shown for three selected patient volunteers. These pilot data suggest that ARFI ultrasound is relevant to monitoring subcutaneous bleeding from femoral arteriotomies clinically and that time to hemostasis was significantly reduced by use of the hemostatic dressing

Acoustic radiation force beam sequence performance for detection and material characterization of atherosclerotic plaques: preclinical, ex vivo results

This work presents preclinical data demonstrating performance of acoustic radiation force (ARF) based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity and specificity for detecting Type III+ plaques (Sens: 85%, Spec: 79%), lipid pools (Sens: 80%, Spec: 86%), fibrous caps (Sens: 86%, spec: 82%), calcium (Sens: 96%, Spec: 85%), collagen (Sens: 78%, Spec: 77%), and disrupted internal elastic lamina (Sens: 92%, Spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg/ml Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of 3-dimensional imaging of a 185 μL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi

Non-invasive in Vivo Characterization of Human Carotid Plaques with Acoustic Radiation Force Impulse Ultrasound: Comparison with Histology after Endarterectomy

Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by noninvasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically-soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that noninvasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case-study format from four patients undergoing clinically-indicated carotid endarterectomy and compared to histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study demonstrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo