Effect of rt-PA on Shear Wave Mechanical Assessment and Quantitative Ultrasound Properties of Blood Clot Kinetics In Vitro.

OBJECTIVE: The consequences associated with blood clots are numerous and are responsible for many deaths worldwide. The assessment of treatment efficacy is necessary for patient follow-up and to detect treatment-resistant patients. The aim of this study was to characterize the effect of treatment on blood clots in vitro using quantitative ultrasound parameters. METHODS: Blood from 10 pigs was collected to form three clots per pig in gelatin phantoms. Clots were subjected to 1) no treatment, 2) rt-PA (recombinant tissue plasminogen activator) treatment after 20 minutes of clotting, and 3) rt-PA treatment after 60 minutes of clotting. Clots were weighted before and after the experiment to assess the treatment effect by the mass loss. The clot kinetics was studied over 100 minutes using elastography (Young's modulus, shear wave dispersion, and shear wave attenuation). Homodyne K-distribution (HKD) parameters derived from speckle statistics were also studied during clot formation and dissolving (diffuse-to-total signal power ratio and intensity parameters). RESULTS: Treated clots loosed significantly more mass than non-treated ones (P < .005). A significant increase in Young's modulus was observed over time (P < .001), and significant reductions were seen for treated clots at 20 or 60 minutes compared with untreated ones (P < .001). The shear wave dispersion differed for treated clots at 60 minutes versus no treatments (P < .001). The shear wave attenuation decreased over time (P < .001), and was different for clots treated at 20 minutes versus no treatments (P < .031). The HKD intensity parameter varied over time (P < .032), and was lower for clots treated at 20 and 60 minutes than those untreated (P < .001 and P < .02). CONCLUSION: The effect of rt-PA treatment could be confirmed by a decrease in Young's modulus and HKD intensity parameter. The shear wave dispersion and shear wave attenuation were sensitive to late and early treatments, respectively. The Young's modulus, shear wave attenuation, and HKD intensity parameter varied over time despite treatment.

Resonance, Velocity, Dispersion, and Attenuation of Ultrasound-Induced Shear Wave Propagation in Blood Clot In Vitro Models.

OBJECTIVE: Improve the characterization of mechanical properties of blood clots. Parameters derived from shear wave (SW) velocity and SW amplitude spectra were determined for gel phantoms and in vitro blood clots. METHODS: Homogeneous phantoms and phantoms with gel or blood clot inclusions of different diameters and mechanical properties were analyzed. SW amplitude spectra were used to observe resonant peaks. Parameters derived from those resonant peaks were related to mimicked blood clot properties. Three regions of interest were tested to analyze where resonances occurred the most. For blood experiments, 20 samples from different pigs were analyzed over time during a 110-minute coagulation period using the Young modulus, SW frequency dispersion, and SW attenuation. RESULTS: The mechanical resonance was manifested by an increase in the number of SW spectral peaks as the inclusion diameter was reduced (P < .001). In blood clot inclusions, the Young modulus increased over time during coagulation (P < .001). Descriptive spectral parameters (frequency peak, bandwidth, and distance between resonant peaks) were linearly correlated with clot elasticity values (P < .001) with R2 = .77 for the frequency peak, .60 for the bandwidth, and .48 for the distance between peaks. The SW dispersion and SW attenuation reflecting the viscous behavior of blood clots decreased over time (P < .001), mainly in the early stage of coagulation (first minutes). CONCLUSION: The confined soft inclusion configuration favored SW mechanical resonances potentially challenging the computation of spectral-based parameters, such as the SW attenuation. The impact of resonances can be reduced by properly selecting the region of interest for data analysis.

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis.

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32ß and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

Non-Invasive Vascular Elastography as a One-Step Imaging Technique to Evaluate Early Vascular Changes in Children Compared to B-Mode-Based Intima-Media Thickness Technique : A Validation Study Using Inter- and Intra-Rater Reliability.

Background: Childhood obesity is linked to higher adult mortality and morbidity from atherosclerosis. It is primordial to detect at-risk children earlier-on to prevent disease progression. Carotid intima-media thickness (IMT) is a subclinical radiological marker for early atherosclerosis. B-mode ultrasound is a known technique to assess IMT, but no gold standard technique exists in children. Non-invasive vascular elastography (NIVE) using speckle statistics is an innovative alternative to evaluate IMT and adds by providing translation, strain and shear strain measurements. Validation studies for both techniques lack in children. Purpose: Validate the reproducibility of the 2 techniques in Canadian children. Methods: We conducted a prospective study where anthropometry, blood pressure, IMT and elastography were measured. Six operators obtained 2 measurements for both carotid arteries using both techniques, for a total of 720 measurements. Inter- and intra-class correlation coefficients (ICC) were calculated for each measurement technique and elastography parameters. Results: 30 participants (13.0 ± 1.26 years, 17 girls) were recruited. Twelve were overweight. No significant difference was found in mean IMT between weight groups for either technique (P = .15 and P = .60). We found excellent inter- (ICC = .98 [95% Confidence Interval (CI): .97; .99]) and intra- (ICC = .90-.93) operator reliability for the B-mode technique, and good inter (ICC = .70 [95% CI: .47; .85]) and intra- (ICC = .71-.91) operator reliability for the NIVE-based technique. Poor reliability was found between techniques (ICC = .30 [95% CI: -.31; .65). For elastography parameters, translation was the most reliable (ICC = .94-.95). Conclusion: IMT measurement is reproducible in children but not between techniques. NIVE gives the advantage of evaluating elastography.

Regional pleural strain measurements during mechanical ventilation using ultrasound elastography: A randomized, crossover, proof of concept physiologic study.

Background: Mechanical ventilation is a common therapy in operating rooms and intensive care units. When ill-adapted, it can lead to ventilator-induced lung injury (VILI), which is associated with poor outcomes. Excessive regional pulmonary strain is thought to be a major mechanism responsible for VILI. Scarce bedside methods exist to measure regional pulmonary strain. We propose a novel way to measure regional pleural strain using ultrasound elastography. The objective of this study was to assess the feasibility and reliability of pleural strain measurement by ultrasound elastography and to determine if elastography parameters would correlate with varying tidal volumes. Methods: A single-blind randomized crossover proof of concept study was conducted July to October 2017 at a tertiary care referral center. Ten patients requiring general anesthesia for elective surgery were recruited. After induction, patients received tidal volumes of 6, 8, 10, and 12 mL.kg-1 in random order, while pleural ultrasound cineloops were acquired at 4 standardized locations. Ultrasound radiofrequency speckle tracking allowed computing various pleural translation, strain and shear components. We screened 6 elastography parameters (lateral translation, lateral absolute translation, lateral strain, lateral absolute strain, lateral absolute shear and Von Mises Strain) to identify those with the best dose-response with tidal volumes using linear mixed effect models. Goodness-of-fit was assessed by the coefficient of determination. Intraobserver, interobserver and test-retest reliability were calculated using intraclass correlation coefficients. Results: Analysis was possible in 90.7% of ultrasound cineloops. Lateral absolute shear, lateral absolute strain and Von Mises strain varied significantly with tidal volume and offered the best dose-responses and data modeling fits. Point estimates for intraobserver reliability measures were excellent for all 3 parameters (0.94, 0.94, and 0.93, respectively). Point estimates for interobserver (0.84, 0.83, and 0.77, respectively) and test-retest (0.85, 0.82, and 0.76, respectively) reliability measures were good. Conclusion: Strain imaging is feasible and reproducible. Future studies will have to investigate the clinical relevance of this novel imaging modality. Clinical trial registration: www.Clinicaltrials.gov, identifier NCT03092557.

Associative Prediction of Carotid Artery Plaques Based on Ultrasound Strain Imaging and Cardiovascular Risk Factors in People Living With HIV and Age-Matched Control Subjects of the CHACS Cohort.

BACKGROUND: There is a need for a specific atherosclerotic risk assessment for people living with HIV (PLWH). SETTING: A machine learning classification model was applied to PLWH and control subjects with low-to-intermediate cardiovascular risks to identify associative predictors of diagnosed carotid artery plaques. Associations with plaques were made using strain elastography in normal sections of the common carotid artery and traditional cardiovascular risk factors. METHODS: One hundred two PLWH and 84 control subjects were recruited from the prospective Canadian HIV and Aging Cohort Study (57 ± 8 years; 159 men). Plaque presence was based on clinical ultrasound scans of left and right common carotid arteries and internal carotid arteries. A classification task for identifying subjects with plaque was defined using random forest (RF) and logistic regression models. Areas under the receiver operating characteristic curves (AUC-ROCs) were applied to select 5 among 50 combinations of 4 or less features yielding the highest AUC-ROCs. RESULTS: To retrospectively classify individuals with and without plaques, the 5 most discriminant combinations of features had AUC-ROCs between 0.76 and 0.79. AUC-ROCs from RF were statistically significantly higher than those obtained with logistic regressions ( P = 0.0001). The most discriminant features of RF classifications in PLWH were age, smoking status, maximum axial strain and pulse pressure (equal weights), and sex and antiretroviral therapy exposure (equal weights). When considering the whole population, the HIV status was identified as a cofactor associated with carotid artery plaques. CONCLUSIONS: Strain elastography adds to traditional cardiovascular risk factors for identifying individuals with carotid artery plaques.

Strain Ultrasound Elastography of Aneurysm Sac Content after Randomized Endoleak Embolization with Sclerosing vs. Non-sclerosing Chitosan-based Hydrogels in a Canine Model.

PURPOSE: To compare the mechanical properties of aneurysm content after endoleak embolization with a chitosan hydrogel (CH) with that with a chitosan hydrogel with sodium tetradecyl sulfate (CH-STS) using strain ultrasound elastography (SUE). MATERIALS AND METHODS: Bilateral common iliac artery type Ia endoleaks were created in 9 dogs. Per animal, 1 endoleak was randomized to blinded embolization with CH, and the other, with CH-STS. Brightness-mode ultrasound, Doppler ultrasound, SUE radiofrequency ultrasound, and computed tomography were performed for up to 6 months until sacrifice. Radiologic and histopathologic studies were coregistered to identify 3 regions of interest: the embolic agent, intraluminal thrombus (ILT), and aneurysm sac. SUE segmentations were performed by 2 blinded independent observers. The maximum axial strain (MAS) was the primary outcome. Statistical analysis was performed using the Fisher exact test, multivariable linear mixed-effects models, and intraclass correlation coefficients (ICCs). RESULTS: Residual endoleaks were identified in 7 of 9 (78%) and 4 of 9 (44%) aneurysms embolized with CH and CH-STS, respectively (P = .3348). CH-STS had a 66% lower MAS (P < .001) than CH. The ILT had a 37% lower MAS (P = .01) than CH and a 77% greater MAS (P = .079) than CH-STS. There was no significant difference in ILT between treatments. The aneurysm sacs embolized with CH-STS had a 29% lower MAS (P < .001) than those embolized with CH. Residual endoleak was associated with a 53% greater MAS (P < .001). The ICC for MAS was 0.807 (95% confidence interval: 0.754-0.849) between segmentations. CONCLUSIONS: CH-STS confers stiffer intraluminal properties to embolized aneurysms. Persistent endoleaks are associated with increased sac strain, an observation that may help guide management.

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.

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.

In vivo Ultrafast Quantitative Ultrasound and Shear Wave Elastography Imaging on Farm-Raised Duck Livers during Force Feeding.

Shear wave elastography (speed and dispersion), local attenuation coefficient slope and homodyned-K parametric imaging were used for liver steatosis grading. These ultrasound biomarkers rely on physical interactions between shear and compression waves with tissues at both macroscopic and microscopic scales. These techniques were applied in a context not yet studied with ultrasound imaging, that is, monitoring steatosis of force-fed duck livers from pre-force-fed to foie gras stages. Each estimated feature presented a statistically significant trend along the feeding process (p values <10-3). However, whereas a monotonic increase in the shear wave speed was observed along the process, most quantitative ultrasound features exhibited an absolute maximum value halfway through the process. As the liver fat fraction in foie gras is much higher than that seen clinically, we hypothesized that a change in the ultrasound scattering regime is encountered for high-fat fractions, and consequently, care has to be taken when applying ultrasound biomarkers to grading of severe states of steatosis.

Increased carotid artery wall stiffness and plaque prevalence in HIV infected patients measured with ultrasound elastography.

OBJECTIVES: Assess carotid artery strain and motion in people living with HIV as markers of premature aging using ultrasound noninvasive vascular elastography (NIVE). METHODS: Seventy-four HIV-infected and 75 age-matched control subjects were recruited from a prospective, controlled cohort study from October 2015 to October 2017 (mean age 56 years ± 8 years; 128 men). NIVE applied to longitudinal ultrasound images of common and internal carotid arteries quantified the cumulated axial strain, cumulated shear strain, cumulated axial translation, and cumulated lateral translations. The presence of plaque was also assessed. An association between elastography biomarkers and HIV status was evaluated with Mann-Whitney tests and multivariable linear regression models. RESULTS: A higher occurrence of carotid artery plaques was found in HIV-infected individuals (p = 0.011). Lower cumulated lateral translations were found in HIV-infected subjects on both common and internal carotid arteries (p = 0.037 and p = 0.026, respectively). These observations remained significant when considering multivariable models including common cardiovascular risk factors and clinical characteristics (p < 0.05). Lower cumulated axial strains were also observed in internal carotid arteries when considering both multivariable models (p < 0.05). CONCLUSION: Lower translation and strain of the carotid artery wall in HIV-infected individuals indicates increased vessel wall stiffness. These new imaging biomarkers could be used to characterize premature atherosclerosis development. KEY POINTS: • Noninvasive vascular elastography (NIVE) based on ultrasound imaging quantifies translations and strains of carotid arteries. • Lower translation and strain of the carotid artery wall found in HIV-infected individuals indicate premature arterial stiffening, compared with age-matched controls. • Carotid artery plaques were more prevalent in HIV-infected individuals than in control subjects.

The value of non-invasive vascular elastography (NIVE) in detecting early vascular changes in overweight and obese children.

OBJECTIVES: Evaluate non-invasive vascular elastography (NIVE) in detecting vascular changes associated with obese children. METHODS: Case-control study to evaluate NIVE in 120 children, 60 with elevated body mass index (BMI) (≥ 85th percentile for age and sex). Participants were randomly selected from a longitudinal cohort, evaluating consequences of obesity in healthy children with one obese parent. Radiofrequency ultrasound videos of the common carotid artery were obtained. The carotid wall was segmented and NIVE applied to measure cumulated axial strain (CAS), cumulated axial translation (CAT), cumulated lateral translation (CLT), maximal shear strain (Max |SSE|), and intima-media thickness (IMT). Multivariate analyses were used controlling for age, sex, Tanner stage, blood pressure, and low-density lipoprotein. Statistical significance was set to 0.05-0.008. Participants were 10-13 years old (mean 11.4 and 12.0, for normal and elevated BMI groups, p < 0.001), 58% and 63% boys, respectively. Groups differed in age, Tanner stage, and blood pressure. In the normal BMI group, there was weak correlation between systolic blood pressure and Max |SSE| (r = 0.316, p = 0.01) and weak correlation between pulse pressure and Max |SSE| (r = 0.259, p = 0.045). After Bonferroni correction, CAT was significantly higher in the elevated BMI group (0.68 ± 0.24 mm vs. 0.52 ± 0.18 mm), p < 0.001. CAS/CAT was significantly lower in the elevated BMI group (9.54 ± 4.8 vs. 13.34 ± 6.46), p = 0.001. IMT was significantly higher in the elevated BMI group (0.36 ± 0.05 mm vs. 0.32 ± 0.05 mm) before Bonferroni correction, p = 0.013. CONCLUSIONS: NIVE detected differences in CAT and CAS/CAT in elevated BMI children. NIVE is a promising technique to monitor radiological markers of subclinical atherosclerosis. KEY POINTS: • NIVE is a non-invasive technique based on measurement of subsegmental focal deformation of vascular wall to detect subclinical changes in arterial wall compliance. • Children with elevated BMI showed increased carotid artery wall movement during systole, as compared to normal BMI children (mean 0.68 ± 0.24 mm vs. 0.52 ± 0.18 mm; p < 0.001) and a lower ratio of vascular wall strain to wall movement during systole (mean 9.54 ± 4.8 vs. 13.34 ± 6.46; p = 0.001). • The detection of these subclinical changes helps physicians in the stratification of children at risk of atherosclerosis and guides in the implementation of preventive measures.

Assessment of Carotid Artery Plaque Components With Machine Learning Classification Using Homodyned-K Parametric Maps and Elastograms.

Quantitative ultrasound (QUS) imaging methods, including elastography, echogenicity analysis, and speckle statistical modeling, are available from a single ultrasound (US) radio-frequency data acquisition. Since these US imaging methods provide complementary quantitative tissue information, characterization of carotid artery plaques may gain from their combination. Sixty-six patients with symptomatic ( n = 26 ) and asymptomatic ( n = 40 ) carotid atherosclerotic plaques were included in the study. Of these, 31 underwent magnetic resonance imaging (MRI) to characterize plaque vulnerability and quantify plaque components. US radio-frequency data sequence acquisitions were performed on all patients and were used to compute noninvasive vascular US elastography and other QUS features. Additional QUS features were computed from three types of images: homodyned-K (HK) parametric maps, Nakagami parametric maps, and log-compressed B-mode images. The following six classification tasks were performed: detection of 1) a small area of lipid; 2) a large area of lipid; 3) a large area of calcification; 4) the presence of a ruptured fibrous cap; 5) differentiation of MRI-based classification of nonvulnerable carotid plaques from neovascularized or vulnerable ones; and 6) confirmation of symptomatic versus asymptomatic patients. Feature selection was first applied to reduce the number of QUS parameters to a maximum of three per classification task. A random forest machine learning algorithm was then used to perform classifications. Areas under receiver-operating curves (AUCs) were computed with a bootstrap method. For all tasks, statistically significant higher AUCs were achieved with features based on elastography, HK parametric maps, and B-mode gray levels, when compared to elastography alone or other QUS alone ( ). For detection of a large area of lipid, the combination yielding the highest AUC (0.90, 95% CI 0.80-0.92, ) was based on elastography, HK, and B-mode gray-level features. To detect a large area of calcification, the highest AUC (0.95, 95% CI 0.94-0.96, ) was based on HK and B-mode gray level features. For other tasks, AUCs varied between 0.79 and 0.97. None of the best combinations contained Nakagami features. This study shows the added value of combining different features computed from a single US acquisition with machine learning to characterize carotid artery plaques.

Two-dimensional affine model-based estimators for principal strain vascular ultrasound elastography with compound plane wave and transverse oscillation beamforming.

Polar strain (radial and circumferential) estimations can suffer from artifacts because the center of a nonsymmetrical carotid atherosclerotic artery, defining the coordinate system in cross-sectional view, can be misregistered. Principal strains are able to remove coordinate dependency to visualize vascular strain components (i.e., axial and lateral strains and shears). This paper presents two affine model-based estimators, the affine phase-based estimator (APBE) developed in the framework of transverse oscillation (TO) beamforming, and the Lagrangian speckle model estimator (LSME). These estimators solve simultaneously the translation (axial and lateral displacements) and deformation (axial and lateral strains and shears) components that were then used to compute principal strains. To improve performance, the implemented APBE was also tested by introducing a time-ensemble estimation approach. Both APBE and LSME were tested with and without the plane strain incompressibility assumption. These algorithms were evaluated on coherent plane wave compounded (CPWC) images considering TO. LSME without TO but implemented with the time-ensemble and incompressibility constraint (Porée et al., 2015) served as benchmark comparisons. The APBE provided better principal strain estimations with the time-ensemble and incompressibility constraint, for both simulations and in vitro experiments. With a few exceptions, TO did not improve principal strain estimates for the LSME. With simulations, the smallest errors compared with ground true measures were obtained with the LSME considering time-ensemble and the incompressibility constraint. This latter estimator also provided the highest elastogram signal-to-noise ratios (SNRs) for in vitro experiments on a homogeneous vascular phantom without any inclusion, for applied strains varying from 0.07% to 4.5%. It also allowed the highest contrast-to-noise ratios (CNRs) for a heterogeneous vascular phantom with a soft inclusion, at applied strains from 0.07% to 3.6%. In summary, the LSME outperformed the implemented APBE, and the incompressibility constraint improved performances of both estimators.

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.

Carotid Artery Plaque Vulnerability Assessment Using Noninvasive Ultrasound Elastography: Validation With MRI.

OBJECTIVE: Vulnerable and nonvulnerable carotid artery plaques have different tissue morphology and composition that may affect plaque biomechanics. The objective of this study is to evaluate plaque vulnerability with the use of ultrasound noninvasive vascular elastography (NIVE). MATERIALS AND METHODS: Thirty-one patients (mean [± SD] age, 69 ± 7 years) with stenosis of the internal carotid artery of 50% or greater were enrolled in this cross-sectional study. Elastography parameters quantifying axial strain, shear strain, and translation motion were used to characterize carotid artery plaques as nonvulnerable, neovascularized, and vulnerable. Maximum axial strain, cumulated axial strain, mean shear strain, cumulated shear strain, cumulated axial translation, and cumulated lateral translations were measured. Cumulated measurements were summed over a cardiac cycle. The ratio of cumulated axial strain to cumulated axial translation was also evaluated. The reference method used to characterize plaques was high-resolution MRI. RESULTS: According to MRI, seven plaques were vulnerable, 12 were nonvulnerable without neovascularity, and 12 were nonvulnerable with neovascularity (a precursor of vulnerability). The two parameters cumulated axial translation and the ratio of cumulated axial strain to cumulated axial translation could discriminate between nonvulnerable plaques and vulnerable plaques or determine the presence of neovascularity in nonvulnerable plaques (which was also possible with the mean shear strain parameter). All parameters differed between the non-vulnerable plaque group and the group that combined vulnerable plaques and plaques with neovascularity. The most discriminating parameter for the detection of vulnerable neovascularized plaques was the ratio of cumulated axial strain to cumulated axial translation (expressed as percentage per millimeter) (mean ratio, 39.30%/mm ± 12.80%/mm for nonvulnerable plaques without neovascularity vs 63.79%/mm ± 17.59%/mm for vulnerable plaques and nonvulnerable plaques with neovascularity, p = 0.002), giving an AUC value of 0.886. CONCLUSION: The imaging parameters cumulated axial translation and the ratio of cumulated axial strain to cumulated axial translation, as computed using NIVE, were able to discriminate vulnerable carotid artery plaques characterized by MRI from nonvulnerable carotid artery plaques. Consideration of neovascularized plaques improved the performance of NIVE. NIVE may be a valuable alternative to MRI for carotid artery plaque assessment.

Assessment of Inter-Expert Variability and of an Automated Segmentation Method of 40 and 60 MHz IVUS Images of Coronary Arteries.

The objectives were to compare the performance of a segmentation algorithm, based on the minimization of an uncertainty function, to delineate contours of external elastic membrane and lumen of human coronary arteries imaged with 40 and 60 MHz IVUS, and to use values of this function to delineate portions of contours with highest uncertainty. For 8 patients, 40 and 60 MHz IVUS coronary data acquired pre- and post-interventions were used, for a total of 68,516 images. Manual segmentations of contours (on 2312 images) performed by experts at three core laboratories were the gold-standards. Inter-expert variability was highest on contour points with largest values of the uncertainty function (p < 0.001). Inter-expert variability was lower at 60 than 40 MHz for external elastic membrane (p = 0.013) and lumen (p = 0.024). Average differences in plaque (and atheroma) burden between algorithmic contours and experts' contours were within inter-expert variability (p < 0.001).

Endovascular Repair of Abdominal Aortic Aneurysm: Follow-up with Noninvasive Vascular Elastography in a Canine Model.

PURPOSE: To assess the ability of noninvasive vascular elastography (NIVE) to help characterize endoleaks and thrombus organization in a canine model of abdominal aortic aneurysm after endovascular aneurysm repair with stent-grafts, in comparison with computed tomography (CT) and pathologic examination findings. MATERIALS AND METHODS: All protocols were approved by the Animal Care Committee in accordance with the guidelines of the Canadian Council of Animal Care. Stent-grafts were implanted in a group of 18 dogs with aneurysms created in the abdominal aorta. Type I endoleak was created in four aneurysms; type II endoleak, in 13 aneurysms; and no endoleak, in one aneurysm. Doppler ultrasonography and NIVE examinations were performed at baseline and at 1-week, 1-month, 3-month, and 6-month follow-up. Angiography, CT, and macroscopic tissue examination were performed at sacrifice. Strain values were computed by using the Lagrangian speckle model estimator. Areas of endoleak, solid organized thrombus, and fresh thrombus were identified and segmented by comparing the results of CT and macroscopic tissue examination. Strain values were compared by using the Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS: All stent-grafts were successfully deployed, and endoleaks were clearly depicted in the last follow-up elastography examinations. Maximal axial strains over consecutive heart cycles in endoleak, organized thrombus, and fresh thrombus areas were 0.78% ± 0.22, 0.23% ± 0.02, 0.10% ± 0.04, respectively. Strain values were significantly different between endoleak and organized or fresh thrombus areas (P < .000) and between organized and fresh thrombus areas (P < .0002). No correlation was found between strain values and type of endoleak, sac pressure, endoleak size, and aneurysm size. CONCLUSION: NIVE may be able to help characterize endoleak and thrombus organization, regardless of the size, pressure, and type of endoleak.

Endovascular shear strain elastography for the detection and characterization of the severity of atherosclerotic plaques: in vitro validation and in vivo evaluation.

This work explores the potential of shear strain elastograms to identify vulnerable atherosclerotic plaques. The Lagrangian speckle model estimator (LSME) elasticity imaging method was further developed to estimate shear strain elasticity (SSE). Three polyvinyl alcohol cryogel vessel phantoms were imaged with an intravascular ultrasound (IVUS) scanner. The estimated SSE maps were validated against finite-element results. Atherosclerosis was induced in carotid arteries of eight Sinclair mini-pigs using a combination of surgical techniques, diabetes and a high-fat diet. IVUS images were acquired in vivo in 14 plaques before euthanasia and histology. All plaques were characterized by high magnitudes in SSE maps that correlated with American Heart Association atherosclerosis stage classifications (r = 0.97, p < 0.001): the worse the plaque condition the higher was the absolute value of SSE, i.e. |SSE| (e.g., mean |SSE| was 3.70 ± 0.40% in Type V plaques, whereas it was reduced to 0.11 ± 0.01% in normal walls). This study indicates the feasibility of using SSE to highlight atherosclerotic plaque vulnerability characteristics.

Segmentation method of intravascular ultrasound images of human coronary arteries.

The goal of this study was to show the feasibility of a 2D segmentation fast-marching method (FMM) in the context of intravascular ultrasound (IVUS) imaging of coronary arteries. The original FMM speed function combines gradient-based contour information and region information, that is the gray level probability density functions of the vessel structures, that takes into account the variability in appearance of the tissues and the lumen in IVUS images acquired at 40 MHz. Experimental results on 38 in vivo IVUS sequences yielded mean point-to-point distances between detected vessel wall boundaries and manual validation contours below 0.11 mm, and Hausdorff distances below 0.33 mm, as evaluated on 3207 images. The proposed method proved to be robust in taking into account various artifacts in ultrasound images: partial shadowing due to calcium inclusions within the plaque, side branches adjacent to the main artery to segment, the presence of a stent, injection of contrast agent or dissection, as tested on 209 images presenting such artifacts.