Shear Wave Elastography and Quantitative Ultrasound as Biomarkers to Characterize Deep Vein Thrombosis In Vivo.

OBJECTIVE: Investigate shear wave elastography (SWE) and quantitative ultrasound (QUS) parameters in patients hospitalized for lower limb deep vein thrombosis (DVT). METHOD: Sixteen patients with DVT were recruited and underwent SWE and radiofrequency data acquisitions for QUS on day 0, day 7, and day 30 after the beginning of symptoms, in both proximal and distal zones of the clot identified on B-mode scan. SWE and QUS features were computed to differentiate between thrombi at day 0, day 7, and day 30 following treatment with heparin or oral anticoagulant. The Young's modulus from SWE was computed, as well as QUS homodyned K-distribution (HKD) parameters reflecting blood clot structure. Median and interquartile range of SWE and QUS parameters within clot were taken as features. RESULTS: In the proximal zone of the clot, the HKD ratio of coherent-to-diffuse backscatter median showed a significant decrease from day 7 to day 30 (P = .036), while the HKD ratio of diffuse-to-total backscatter median presented a significant increase from day 7 to day 30 (P = .0491). In the distal zone of the clot, the HKD normalized intensity of the echo envelope median showed a significant increase from day 0 to day 30 (P = .0062). No SWE features showed statistically significant differences over time. Nonetheless, a trend of lower median of Young's modulus within clot for patients who developed a pulmonary embolism was observed. CONCLUSION: QUS features may be relevant to characterize clot's evolution over time. Further analysis of their clinical interpretation and validation on a larger dataset would deserve to be studied.

Impact of Applying a Skin Compression With the Ultrasound Probe on Carotid Artery Strain Elastography.

OBJECTIVE: To study the impact of varying the external compression exerted by the ultrasound probe when performing a carotid strain elastography exam. METHODS: Nine healthy volunteers (mean age 43 years ±13 years; 6 men) underwent a vascular ultrasound elastography exam using a custom made sound feedback handle embedding the probe, and allowing the sonographer to adjust the applied compression. A clinical standard practice (SP) force was first recorded, and then predetermined compression (PDC) forces were applied, ranging from 0 to 5 N for the left common carotid artery (CCA) or 2-12 N for the left internal carotid artery (ICA). Six carotid elastography features, namely maximum and cumulated axial strains, maximum and cumulated shear strains, cumulated axial translation, and cumulated lateral translation were assessed with noninvasive vascular elastography (NIVE) on near and far walls of carotids. The carotid intima media thickness (IMT) and diameter were also measured. RESULTS: All elastography features on the near wall of both CCA and ICA decreased statistically significantly as the PDC force increased; this association was also observed for half of the features on the far wall. Three NIVE features at the lowest PDC force (out of 72 that were tested) were statistically significantly different than values at the SP force. Overall, NIVE showed some variance to probe compression with linear regression slopes revealing changes of 10.1%-45.6% in magnitude over the whole compression range on both walls. The maximum IMT for the ICA near wall, and carotid lumen diameters of both CCA and ICA were statistically significantly associated with PDC forces; these features underwent a decrease of 10.2%, 36.2%, and 17.6%, respectively, over the whole range of PDC force increase. Other IMT measurements were not statistically significantly associated with applied PDC forces. CONCLUSION: These results suggest the need of technical guidelines for carotid strain elastography. Using the lowest probe compression while allowing a good B-mode image quality is recommended to improve the robustness of NIVE measurements.

Estimation of polydispersity in aggregating red blood cells by quantitative ultrasound backscatter analysis.

Quantitative ultrasound techniques based on the backscatter coefficient (BSC) have been commonly used to characterize red blood cell (RBC) aggregation. Specifically, a scattering model is fitted to measured BSC and estimated parameters can provide a meaningful description of the RBC aggregates' structure (i.e., aggregate size and compactness). In most cases, scattering models assumed monodisperse RBC aggregates. This study proposes the Effective Medium Theory combined with the polydisperse Structure Factor Model (EMTSFM) to incorporate the polydispersity of aggregate size. From the measured BSC, this model allows estimating three structural parameters: the mean radius of the aggregate size distribution, the width of the distribution, and the compactness of the aggregates. Two successive experiments were conducted: a first experiment on blood sheared in a Couette flow device coupled with an ultrasonic probe, and a second experiment, on the same blood sample, sheared in a plane-plane rheometer coupled to a light microscope. Results demonstrated that the polydisperse EMTSFM provided the best fit to the BSC data when compared to the classical monodisperse models for the higher levels of aggregation at hematocrits between 10% and 40%. Fitting the polydisperse model yielded aggregate size distributions that were consistent with direct light microscope observations at low hematocrits.

The Added Value of Statistical Modeling of Backscatter Properties in the Management of Breast Lesions at US.

PURPOSE: To develop a classification method based on the statistical backscatter properties of tissues that can be used as an ancillary tool to the usual Breast Imaging Reporting and Data System (BI-RADS) classification for solid breast lesions identified at ultrasonography (US). MATERIALS AND METHODS: This study received institutional review board approval, and all subjects provided informed consent. Eighty-nine women (mean age, 50 years; age range, 22-82 years) with 96 indeterminate solid breast lesions (BI-RADS category 4-5; mean size, 13.2 mm; range, 2.6-44.7 mm) were enrolled. Prior to biopsy, additional radiofrequency US images were obtained, and a 3-second cine sequence was used. The research data were analyzed at a later time and were not used to modify patient management decisions. The lesions were segmented manually, and parameters of the homodyned K distribution (α, k, and µn values) were extracted for three regions: the intratumoral zone, a 3-mm supratumoral zone, and a 5-mm infratumoral zone. The Mann-Whitney rank sum test was used to identify parameters with the best discriminating value, yielding intratumoral α, supratumoral k, and infratumoral µn values. RESULTS: The 96 lesions were classified as follows: 48 BI-RADS category 4A lesions, 16 BI-RADS category 4B lesions, seven BI-RADS category 4C lesions, and 25 BI-RADS category 5 lesions. There were 24 cancers (25%). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval: 0.65, 0.86). Overall, 24% of biopsies (in 17 of 72 lesions) could have been spared. By limiting analysis to lesions with a lower likelihood of malignancy (BI-RADS category 4A-4B), this percentage increased to 26% (16 of 62 lesions). Among benign lesions, the model was used to correctly classify 10 of 38 fibroadenomas (26%) and three of seven stromal fibroses (43%). CONCLUSION: The statistical model performs well in the classification of solid breast lesions at US, with the potential of preventing one in four biopsies without missing any malignancy.

Ultrasound monitoring of RBC aggregation as a real-time marker of the inflammatory response in a cardiopulmonary bypass swine model.

OBJECTIVES: In many pathological conditions, including high-risk surgery, the severity of the inflammatory response is related to the patient outcome. However, determining the patient inflammatory state presents difficulties, as markers are obtained intermittently through blood testing with long delay. RBC aggregation is a surrogate marker of inflammation that can be quantified with the ultrasound Structure Factor Size and Attenuation Estimator. The latter is proposed as a real-time inflammation monitoring technique for patient care. DESIGN: Ten swine underwent a 90-minute cardiopulmonary bypass, and surveillance was maintained during 120 minutes in the postbypass period. To promote the inflammatory reaction, lipopolysaccharide was administrated two times prior to surgery in six of those swine (lipopolysaccharide group). During the whole procedure, the Structure Factor Size and Attenuation Estimator cellular imaging method displayed a RBC aggregation index (W) computed from images acquired within the pump circuit and the femoral vein. Interleukin-6, interleukin-10, C-reactive protein, haptoglobin, immunoglobulin G, and fibrinogen concentrations were measured at specific periods. MAIN RESULTS: Compared with controls, the lipopolysaccharide group exhibited higher W within the pump circuit (p < 0.05). In the femoral vein, W was gradually amplified in the lipopolysaccharide group during cardiopulmonary bypass and the postbypass period (p < 0.05), whereas interleukin levels were higher in the lipopolysaccharide group but only at the end of cardiopulmonary bypass and beginning of postbypass (p < 0.05). CONCLUSIONS: Continuous RBC aggregation monitoring can characterize the evolving inflammatory response during and after cardiopulmonary bypass. The Structure Factor Size and Attenuation Estimator is proposed as a real-time noninvasive monitoring technique to anticipate inflammation-related complications during high-risk surgery or critical care situations. Because RBC aggregation promotes vascular resistance and thrombosis, W could also provide early information on vascular disorders in those clinical situations.

Ultrasound Shear Wave Attenuation Imaging for Grading Liver Steatosis in Volunteers and Patients With Non-alcoholic Fatty Liver Disease: A Pilot Study.

OBJECTIVE: The aims of the work described here were to assess shear wave attenuation (SWA) in volunteers and patients with non-alcoholic fatty liver disease (NAFLD) and compare its diagnostic performance with that of shear wave dispersion (SWD), magnetic resonance imaging (MRI) proton density fat fraction (PDFF) and biopsy. METHODS: Forty-nine participants (13 volunteers and 36 NAFLD patients) were enrolled. Ultrasound and MRI examinations were performed in all participants. Biopsy was also performed in patients. SWA was used to assess histopathology grades as potential confounders. The areas under curves (AUCs) of SWA, SWD and MRI-PDFF were assessed in different steatosis grades by biopsy. Youden's thresholds of SWA were obtained for steatosis grading while using biopsy or MRI-PDFF as the reference standard. RESULTS: Spearman's correlations of SWA with histopathology (steatosis, inflammation, ballooning and fibrosis) were 0.89, 0.73, 0.62 and 0.31, respectively. Multiple linear regressions of SWA confirmed the correlation with steatosis grades (adjusted R2 = 0.77, p < 0.001). The AUCs of MRI-PDFF, SWA and SWD were respectively 0.97, 0.99 and 0.94 for S0 versus ≥S1 (p > 0.05); 0.94, 0.98 and 0.78 for ≤S1 versus ≥S2 (both MRI-PDFF and SWA were higher than SWD, p < 0.05); and 0.90, 0.93 and 0.68 for ≤S2 versus S3 (both SWA and MRI-PDFF were higher than SWD, p < 0.05). SWA's Youden thresholds (Np/m/Hz) (sensitivity, specificity) for S0 versus ≥S1, ≤S1 versus ≥S2 and ≤S2 versus S3 were 1.05 (1.00, 0.92), 1.37 (0.96, 0.96) and 1.51 (0.83, 0.87), respectively. These values were 1.16 (1.00, 0.81), 1.49 (0.91, 0.82) and 1.67 (0.87, 0.92) when considering MRI-PDFF as the reference standard. CONCLUSION: In this pilot study, SWA increased with increasing steatosis grades, and its diagnostic performance was higher than that of SWD but equivalent to that of MRI-PDFF.

Ultrafast Myocardial Principal Strain Ultrasound Elastography During Stress Tests: In Vitro Validation and In Vivo Feasibility.

Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.

Deformability of ascending thoracic aorta aneurysms assessed using ultrafast ultrasound and a principal strain estimator: In vitro evaluation and in vivo feasibility.

BACKGROUND: Noninvasive vascular strain imaging under conventional line-by-line scanning has a low frame rate and lateral resolution and depends on the coordinate system. It is thus affected by high deformations due to image decorrelation between frames. PURPOSE: To develop an ultrafast time-ensemble regularized tissue-Doppler optical-flow principal strain estimator for aorta deformability assessment in a long-axis view. METHODS: This approach alleviated the impact of lateral resolution using image compounding and that of the coordinate system dependency using principal strain. Accuracy and feasibility were evaluated in two aorta-mimicking phantoms first, and then in four age-matched individuals with either a normal aorta or a pathological ascending thoracic aorta aneurysm (TAA). RESULTS: Instantaneous aortic maximum and minimum principal strain maps and regional accumulated strains during each cardiac cycle were estimated at systolic and diastolic phases to characterize the normal aorta and TAA. In vitro, principal strain results matched sonomicrometry measurements. In vivo, a significant decrease in maximum and minimum principal strains was observed in TAA cases, whose range was respectively 7.9 ± 6.4% and 8.2 ± 2.6% smaller than in normal aortas. CONCLUSIONS: The proposed principal strain estimator showed an ability to potentially assess TAA deformability, which may provide an individualized and reliable evaluation method for TAA rupture risk assessment.

Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease.

OBJECTIVE: To develop a quantitative ultrasound (QUS)- and elastography-based model to improve classification of steatosis grade, inflammation grade, and fibrosis stage in patients with chronic liver disease in comparison with shear wave elastography alone, using histopathology as the reference standard. METHODS: This ancillary study to a prospective institutional review-board approved study included 82 patients with non-alcoholic fatty liver disease, chronic hepatitis B or C virus, or autoimmune hepatitis. Elastography measurements, homodyned K-distribution parametric maps, and total attenuation coefficient slope were recorded. Random forests classification and bootstrapping were used to identify combinations of parameters that provided the highest diagnostic accuracy. Receiver operating characteristic (ROC) curves were computed. RESULTS: For classification of steatosis grade S0 vs. S1-3, S0-1 vs. S2-3, S0-2 vs. S3, area under the receiver operating characteristic curve (AUC) were respectively 0.60, 0.63, and 0.62 with elasticity alone, and 0.90, 0.81, and 0.78 with the best tested model combining QUS and elastography features. For classification of inflammation grade A0 vs. A1-3, A0-1 vs. A2-3, A0-2 vs. A3, AUCs were respectively 0.56, 0.62, and 0.64 with elasticity alone, and 0.75, 0.68, and 0.69 with the best model. For classification of liver fibrosis stage F0 vs. F1-4, F0-1 vs. F2-4, F0-2 vs. F3-4, F0-3 vs. F4, AUCs were respectively 0.66, 0.77, 0.72, and 0.74 with elasticity alone, and 0.72, 0.77, 0.77, and 0.75 with the best model. CONCLUSION: Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.

Parameterized Strain Estimation for Vascular Ultrasound Elastography With Sparse Representation.

Ultrasound vascular strain imaging has shown its potential to interrogate the motion of the vessel wall induced by the cardiac pulsation for predicting plaque instability. In this study, a sparse model strain estimator (SMSE) is proposed to reconstruct a dense strain field at a high resolution, with no spatial derivatives, and a high computation efficiency. This sparse model utilizes the highly-compacted property of discrete cosine transform (DCT) coefficients, thereby allowing to parameterize displacement and strain fields with truncated DCT coefficients. The derivation of affine strain components (axial and lateral strains and shears) was reformulated into solving truncated DCT coefficients and then reconstructed with them. Moreover, an analytical solution was derived to reduce estimation time. With simulations, the SMSE reduced estimation errors by up to 50% compared with the state-of-the-art window-based Lagrangian speckle model estimator (LSME). The SMSE was also proven to be more robust than the LSME against global and local noise. For in vitro and in vivo tests, residual strains assessing cumulated errors with the SMSE were 2 to 3 times lower than with the LSME. Regarding computation efficiency, the processing time of the SMSE was reduced by 4 to 25 times compared with the LSME, according to simulations, in vitro and in vivo results. Finally, phantom studies demonstrated the enhanced spatial resolution of the proposed SMSE algorithm against LSME.

Anthropomorphic and biomechanical mockup for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is an asymptomatic condition due to the dilation of abdominal aorta along with progressive wall degeneration, where rupture of AAA is life-threatening. Failures of AAA endovascular repair (EVAR) reflect our inadequate knowledge about the complex interaction between the aortic wall and medical devices. In this regard, we are presenting a hydrogel-based anthropomorphic mockup (AMM) to better understand the biomechanical constraints during EVAR. By adjusting the cryogenic treatments, we tailored the hydrogel to mimic the mechanical behavior of human AAA wall, thrombus and abdominal fat. A specific molding sequence and a pressurizing system were designed to reproduce the geometrical and diseased characteristics of AAA. A mechanically, anatomically and pathologically realistic AMM for AAA was developed for the first time, EVAR experiments were then performed with and without the surrounding fat. Substantial displacements of the aortic centerlines and vessel expansion were observed in the case without surrounding fat, revealing an essential framework created by the surrounding fat to account for the interactions with medical devices. In conclusion, the importance to consider surrounding tissue for the global deformation of AAA during EVAR was highlighted. Furthermore, potential use of this AMM for medical training was also suggested.

Pilot clinical study of quantitative ultrasound spectroscopy measurements of erythrocyte aggregation within superficial veins.

BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S10). RESULTS: W and Din vivo measurements were positively correlated with the ex vivoS10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

Added Value of Quantitative Ultrasound and Machine Learning in BI-RADS 4-5 Assessment of Solid Breast Lesions.

The purpose of this study was to evaluate various combinations of 13 features based on shear wave elasticity (SWE), statistical and spectral backscatter properties of tissues, along with the Breast Imaging Reporting and Data System (BI-RADS), for classification of solid breast lesions at ultrasonography by means of random forests. One hundred and three women with 103 suspicious solid breast lesions (BI-RADS categories 4-5) were enrolled. Before biopsy, additional SWE images and a cine sequence of ultrasound images were obtained. The contours of lesions were delineated, and parametric maps of the homodyned-K distribution were computed on three regions: intra-tumoral, supra-tumoral and infra-tumoral zones. Maximum elasticity and total attenuation coefficient were also extracted. Random forests yielded receiver operating characteristic (ROC) curves for various combinations of features. Adding BI-RADS category improved the classification performance of other features. The best result was an area under the ROC curve of 0.97, with 75.9% specificity at 98% sensitivity.

Multimodality vascular imaging phantoms: a new material for the fabrication of realistic 3D vessel geometries.

Multimodality vascular flow phantoms provide a way of testing the geometric accuracy of clinical scanners and optimizing acquisition protocols with easy reproducibility of experimental conditions. This article presents a stereolithography method combined with a lost-material casting technique that eliminates metal residues of cerrolow (a low temperature melting point metallic alloy) left within irregular vessel lumens after casting. These residues potentially cause image artifacts especially in magnetic resonance angiography or flow disturbance. Geometrical accuracies of constructed lumens with isomalt, the proposed material, ranged from 3.3% to 5.7% for vessel diameters of 1.8-7.9 mm, which are comparable to those of lumens constructed with cerrolow that had better accuracies varying from 1.1% to 4.1% (p<0.02). Examples of geometries mimicking diseased arteries such as an aorta with stenosed renal arteries and an iliac artery with multiple stenoses are presented. This sugar-based isomalt material, combined with phantom designs having fiducial markers visible in digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and ultrasound [Med. Phys. 31, 1424-1433 (2004)], makes easier the fabrication of complex realistic and accurate replicas of pathological vessels with lumen irregularities.

Reconstruction of Viscosity Maps in Ultrasound Shear Wave Elastography.

Change in viscoelastic properties of biological tissues may often be symptomatic of a dysfunction that can be correlated to tissue pathology. Shear wave elastography is an imaging method mainly used to assess stiffness but with the potential to measure viscoelasticity of biological tissues. This can enable tissue characterization; and thus, can be used as a marker to improve diagnosis of pathological lesions. In this study, a frequency-shift method based framework is presented for the reconstruction of viscosity by analyzing the spectral properties of acoustic radiation force-induced shear waves. The aim of the study was to investigate the feasibility of viscosity reconstruction maps in homogeneous as well as heterogeneous samples. Experiments were performed in four in vitro phantoms, two ex vivo porcine liver samples, two ex vivo fatty duck liver samples, and one in vivo fatty goose liver. Successful viscosity maps were reconstructed in homogeneous and heterogeneous phantoms with embedded mechanical inclusions having different geometries. Quantitative values of viscosity obtained for two porcine liver tissues, two fatty duck liver samples, and one goose fatty liver were (mean ± SD) 0.61 ± 0.21, 0.52 ± 0.35; 1.28 ± 0.54, 1.36 ± 0.73, and 1.67 ± 0.70 Pa.s, respectively.

Atherosclerotic carotid bifurcation phantoms with stenotic soft inclusions for ultrasound flow and vessel wall elastography imaging.

As the complexity of ultrasound signal processing algorithms increases, it becomes more difficult to demonstrate their added value and thus robust validation strategies are required. We propose a method of manufacturing ultrasonic vascular phantoms mimicking an atheromatous plaque in an internal carotid artery bifurcation for applications in flow imaging and elastography. During the fabrication process, a soft inclusion mimicking a stenotic lipid pool was embedded within the vascular wall. Mechanical testing measured Young's moduli of the vascular wall and soft inclusion at 342 ± 25 kPa and 17 ± 3 kPa, respectively. B-mode, color Doppler, power Doppler, shear wave elastography, and strain elastography images of the different phantoms were produced to show the validity of the fabrication process. Because of their realistic geometries and mechanical properties, those phantoms may become advantageous for fluid-structure experimental modeling and validation of new ultrasound-based imaging technologies.

Acoustic radiation force induced resonance elastography of coagulating blood: theoretical viscoelasticity modeling and ex-vivo experimentation.

Deep vein thrombosis is a common vascular disease that can lead to pulmonary embolism and death. The early diagnosis and clot age staging are important parameters for reliable therapy planning. This article presents an acoustic radiation force induced resonance elastography method for the viscoelastic characterization of clotting blood. The physical concept of this method relies on the mechanical resonance of the blood clot occurring at specific frequencies. Resonances are induced by focusing ultrasound beams inside the sample under investigation. Coupled to an analytical model of wave scattering, the ability of the proposed method to characterize the viscoelasticity of a mimicked venous thrombosis in the acute phase is demonstrated. Experiments with a gelatin-agar inclusion sample of known viscoelasticity are performed for validation and establishment of the proof of concept. In addition, an inversion method is applied in-vitro for the kinetic monitoring of the blood coagulation process of six human blood samples obtained from two volunteers. The computed elasticity and viscosity values of blood samples at the end of the 90 min kinetics were estimated at 411 ± 71 Pa and 0.25 ± 0.03 Pa.s for volunteer #1, and 387 ± 35 Pa and 0.23 ± 0.02 Pa.s for volunteer #2, respectively. The proposed method allowed reproducible time-varying thrombus viscoelastic measurements from samples having physiological dimensions.

Investigation of out-of-plane motion artifacts in 2D noninvasive vascular ultrasound elastography.

Ultrasound noninvasive vascular elastography (NIVE) has shown its potential to measure strains of carotid arteries to predict plaque instability. When two-dimensional (2D) strain estimation is performed, either in longitudinal or cross-sectional view, only in-plane motions are considered. The motions in elevation direction (i.e. perpendicular to the imaging plane), can induce estimation artifacts affecting the accuracy of 2D NIVE. The influence of such out-of-plane motions on the performance of axial strain and axial shear strain estimations has been evaluated in this study. For this purpose, we designed a diseased carotid bifurcation phantom with a 70% stenosis and an in vitro experimental setup to simulate orthogonal out-of-plane motions of 1 mm, 2 mm and 3 mm. The Lagrangian speckle model estimator (LSME) was used to estimate axial strains and shears under pulsatile conditions. As anticipated, in vitro results showed more strain estimation artifacts with increasing magnitudes of motions in elevation. However, even with an out-of-plane motion of 2.0 mm, strain and shear estimations having inter-frame correlation coefficients higher than 0.85 were obtained. To verify findings of in vitro experiments, a clinical LSME dataset obtained from 18 participants with carotid artery stenosis was used. Deduced out-of-plane motions (ranging from 0.25 mm to 1.04 mm) of the clinical dataset were classified into three groups: small, moderate and large elevational motions. Clinical results showed that pulsatile time-varying strains and shears remained reproducible for all motion categories since inter-frame correlation coefficients were higher than 0.70, and normalized cross-correlations (NCC) between radiofrequency (RF) images were above 0.93. In summary, the performance of LSME axial strain and shear estimations appeared robust in the presence of out-of-plane motions (<2 mm) as encountered during clinical ultrasound imaging.

Accuracy of speckle tracking in the context of stress echocardiography in short axis view: An in vitro validation study.

AIM: This study aimed to test the accuracy of a speckle tracking algorithm to assess myocardial deformation in a large range of heart rates and strain magnitudes compared to sonomicrometry. METHODS AND RESULTS: Using a tissue-mimicking phantom with cyclic radial deformation, radial strain derived from speckle tracking (RS-SpT) of the upper segment was assessed in short axis view by conventional echocardiography (Vivid q, GE) and post-processed with clinical software (EchoPAC, GE). RS-SpT was compared with radial strain measured simultaneously by sonomicrometers (RS-SN). Radial strain was assessed with increasing deformation rates (60 to 160 beats/min) and increasing pulsed volumes (50 to 100 ml/beat) to simulate physiological changes occurring during stress echocardiography. There was a significant correlation (R2 = 0.978, P <0.001) and a close agreement (bias ± 2SD, 0.39 ± 1.5%) between RS-SpT and RS-SN. For low strain values (<15%), speckle tracking showed a small but significant overestimation of radial strain compared to sonomicrometers. Two-way analysis of variance did not show any significant effect of the deformation rate. For RS-SpT, the feasibility was excellent and the intra- and inter-observer variability were low (the intraclass correlation coefficients were 0.96 and 0.97, respectively). CONCLUSIONS: Speckle tracking demonstrated a good correlation with sonomicrometry for the assessment of radial strain independently of the heart rate and strain magnitude in a physiological range of values. Though speckle tracking seems to be a reliable and reproducible technique to assess myocardial deformation variations during stress echocardiography, further studies are mandated to analyze the impact of angulated and artefactual out-of-plane motions and inter-vendor variability.

Projected valve area at normal flow rate improves the assessment of stenosis severity in patients with low-flow, low-gradient aortic stenosis: the multicenter TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study.

BACKGROUND: We sought to investigate the use of a new parameter, the projected effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. METHODS AND RESULTS: The use of EOAproj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection fraction < or =40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOAproj was calculated as EOAproj=EOArest+VCx(250-Q(rest)), where EOArest and Q(rest) are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOAproj and 91% for indexed EOAproj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. CONCLUSIONS: EOAproj provides a standardized evaluation of AS severity with DSE and improves the diagnostic accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient AS.