Search

A significant risk factor for ischemic stroke is carotid atherosclerotic plaque that is susceptible to rupture, with rupture potential conveyed by plaque morphology. Human carotid plaque composition and structure have been delineated noninvasively and in vivo by evaluating log(VoA), a parameter derived as the decadic log of the second time derivative of displacement induced by an acoustic radiation force impulse (ARFI). In prior work, ARFI-induced displacement was measured using conventional focused tracking; however, this requires a long data acquisition period, thereby reducing framerate. We herein evaluate if ARFI log(VoA) framerate can be increased without a reduction in plaque imaging performance using plane wave tracking instead. In silico, both focused- and plane wave-tracked log(VoA) decreased with increasing echobrightness, quantified as signal-to-noise ratio (SNR), but did not vary with material elasticity for SNRs below 40 dB. For SNRs of 40-60 dB, both focused- and plane wave-tracked log(VoA) varied with SNR and material elasticity. Above 60 dB SNR, both focused- and plane wave-tracked log(VoA) varied with material elasticity alone. This suggests that log(VoA) discriminates features according to a combination of their echobrightness and mechanical property. Further, while both focused- and plane-wave tracked log(VoA) values were artifactually inflated by mechanical reflections at inclusion boundaries, plane wave-tracked log(VoA) was more strongly impacted by off-axis scattering. Applied to three excised human cadaveric carotid plaques with spatially aligned histological validation, both log(VoA) methods detected regions of lipid, collagen, and calcium (CAL) deposits. These findings support that plane wave tracking performs comparably to focused tracking for log(VoA) imaging and that plane wave-tracked log(VoA) is a viable approach to discriminating clinically relevant atherosclerotic plaque features at a 30-fold higher framerate than by focused tracking.

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, in vivo. Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher ( , Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated ( R 2 = 0.95 ) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed ( p > 0.01 ). Similar results were demonstrated in vivo in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference ( p > 0.01 ) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population ( p > 0.01 ). The results of this pilot in vivo clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.

While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed "log(VoA)," was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management.

Our group has previously found that in silico, mechanical anisotropy may be interrogated by exciting transversely isotropic materials with geometrically asymmetric acoustic radiation force excitations and then monitoring the associated induced displacements in the region of excitation. We now translate acoustic radiation force-based anisotropy assessment to human muscle in vivo and investigate its clinical relevance to monitoring muscle degeneration in Duchenne muscular dystrophy (DMD). Clinical anisotropy assessments were performed using Viscoelastic Response ultrasound, with a degree of anisotropy reflected by the ratios of Viscoelastic Response relative elasticity (RE) or relative viscosity (RV) measured with the asymmetric radiation force oriented parallel versus perpendicular to muscle fiber alignment. In vivo results from rectus femoris and gastrocnemius muscles of boys aged ∼7.9-10.4 y indicate that RE and RV anisotropy ratios in rectus femoris muscles of boys with DMD were significantly higher than those of healthy control boys (RE: DMD = 1.51 ± 0.87, control = 0.99 ± 0.69, p = 0.04, Wilcoxon rank sum test; RV: DMD = 1.04 ± 0.71, control = 0.74 ± 0.22, p = 0.02). In the gastrocnemius muscle, only the RV anisotropy ratio was significantly higher in dystrophic than control patients (DMD = 1.23 ± 0.35, control = 0.88 ± 0.31, p = 0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope = -0.03/lbf, r = -0.43, p = 0.07, Pearson correlation) with quantitative muscle testing functional output measures but was not correlated with quantitative muscle testing in the dystrophic gastrocnemius. These results suggest that Viscoelastic Response RE and RV measures reflect differences in mechanical anisotropy associated with functional impairment with dystrophic degeneration that are relevant to monitoring DMD clinically., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Objective: Stroke is commonly caused by thromboembolic events originating from ruptured carotid plaque with vulnerable composition. This study assessed the performance of acoustic radiation force impulse (ARFI) imaging, a noninvasive ultrasound elasticity imaging method, for delineating the composition of human carotid plaque in vivo with histologic validation., Methods: Carotid ARFI images were captured before surgery in 25 patients undergoing clinically indicated carotid endarterectomy. The surgical specimens were histologically processed with sectioning matched to the ultrasound imaging plane. Three radiologists, blinded to histology, evaluated parametric images of ARFI-induced peak displacement to identify plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), calcium (CAL), and fibrous cap (FC) thickness. Reader performance was measured against the histologic standard using receiver operating characteristic curve analysis, linear regression, Spearman correlation (ρ), and Bland-Altman analysis., Results: ARFI peak displacement was two-to-four-times larger in regions of NC and IPH relative to regions of COL or CAL. Readers detected soft plaque features (NC/IPH) with a median area under the curve of 0.887 (range, 0.867-0.924) and stiff plaque features (COL/CAL) with median area under the curve of 0.859 (range, 0.771-0.929). FC thickness measurements of two of the three readers correlated with histology (reader 1: R 2  = 0.64, ρ = 0.81; reader 2: R 2  = 0.89, ρ = 0.75)., Conclusions: This study suggests that ARFI is capable of distinguishing soft from stiff atherosclerotic plaque components and delineating FC thickness., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Acoustic radiation force impulse (ARFI) Surveillance of Subcutaneous Hemorrhage (ASSH) has been previously demonstrated to differentiate bleeding phenotype and responses to therapy in dogs and humans, but to date, the method has lacked experimental validation. This work explores experimental validation of ASSH in a poroelastic tissue-mimic and in vivo in dogs. The experimental design exploits calibrated flow rates and infusion durations of evaporated milk in tofu or heparinized autologous blood in dogs. The validation approach enables controlled comparisons of ASSH-derived bleeding rate (BR) and time to hemostasis (TTH) metrics. In tissue-mimicking experiments, halving the calibrated flow rate yielded ASSH-derived BRs that decreased by 44% to 48%. Furthermore, for calibrated flow durations of 5.0 minutes and 7.0 minutes, average ASSH-derived TTH was 5.2 minutes and 7.0 minutes, respectively, with ASSH predicting the correct TTH in 78% of trials. In dogs undergoing calibrated autologous blood infusion, ASSH measured a 3-minute increase in TTH, corresponding to the same increase in the calibrated flow duration. For a measured 5% decrease in autologous infusion flow rate, ASSH detected a 7% decrease in BR. These tissue-mimicking and in vivo preclinical experimental validation studies suggest the ASSH BR and TTH measures reflect bleeding dynamics., (© The Author(s) 2015.)

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 non-invasive 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 non-invasively 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 for four patients undergoing clinically indicated carotid endarterectomy and compared with 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 were 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 illustrates 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., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

A validated method for assessing hemostasis in vivo is critical for testing the hemostatic efficacy of therapeutic agents designed for patients with bleeding disorders such as von Willebrand disease (VWD) and hemophilia A. We hypothesize that rate of bleeding and time to hemostasis can be monitored in vivo by acoustic radiation force impulse (ARFI) ultrasound. We performed ARFI imaging following 12-gauge needle puncture of hind limb muscle encompassing an ∼2 mm vein in six normal, eight naïve hemophilia A before and after infusing canine factor VIII, three hemophilia A expressing canine factor VIIa following gene transfer, and two naïve VWD dogs. Serial data sets were processed with custom software to (1) estimate the rate of hemorrhage and (2) estimate the time of hemostasis onset. The rate of hemorrhage during the first 30 min following puncture was markedly increased in the VWD dogs relative to normal but was not significantly different between normal, naïve hemophilia A or hemophilia A expressing cFVIIa. ARFI-derived times to hemostasis were significantly longer in naïve hemophilia A dogs than in normal dogs and were shortened by canine coagulation factors VIII and VIIa. These data support our hypothesis that rate of hemorrhage and time to hemostasis in vivo in response to a standardized hemostatic challenge can be detected by ARFI ultrasound in canine models of VWD and hemophilia. These data also suggest that the ARFI-monitored hemostatic challenge is relevant for in vivo testing of the hemostatic efficacy of therapeutic clotting factor replacement products used to treat inherited bleeding disorders., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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.