Gray-scale Median Research Articles

Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes

BackgroundThe association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages.MethodsWe conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics.ResultsAmong 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, β = − 5.822; 95% CI − 8.875 to − 2.768, P < 0.001), glucose coefficient of variation (β = − 0.418; − 0.685 to − 0.151, P = 0.002), mean amplitude of glycemic excursion (β = − 1.689; − 2.567 to − 0.811, P < 0.001), mean of daily differences (β = − 6.500; − 9.758 to − 3.241, P < 0.001), and interquartile range (β = − 4.289; − 6.964 to − 1.614, P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT.ConclusionsContinuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.

Carotid plaque vulnerability assessed by Shear Wave elastography and ultrafast Doppler compared to histology: The UF-plaque study

Ultrafast Ultrasound Imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 hours before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray Scale Median analysis by B mode, mean and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques ( P = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the Receiver Operating Characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques.

Carotid plaque inflammatory activity assessed by 2-[18F]FDG-PET imaging decrease after a neurological thromboembolic event

BackgroundAtherosclerotic plaque vulnerability is comprised by plaque composition driven by inflammatory activity and these features can be depicted with 3D ultrasound and 2-[18F]FDG-PET, respectively. The study investigated timely changes in carotid artery plaque inflammation and morphology after a thromboembolic event with PET/CT and novel ultrasound volumetric grayscale median (GSM) readings. Patients with a single hemisphere-specific neurological symptom and the presence of an ipsilateral carotid artery atherosclerotic plaque were prospectively included to both 2-[18F]FDG PET/CT and 3D ultrasound scans of the plaque immediately after their event and again three months later. On PET/CT images the maximum standardized uptake value (SUVmax) was measured and the volumetric ultrasound acquisitions were analyzed using a semiautomated software measuring GSM values.ResultsBaseline scans were performed by a mean of 7 days (range 2–14) after the symptom and again after 98 days (range 91–176). For the entire group (n = 14), we found a decrease in average SUVmax from baseline to follow-up of − 0.18 (95% confidence interval: − 0.34 to − 0.02, P = 0.034). GSM did not increase significantly over time (mean change: + 2.21, 95% confidence interval: − 17.02 to 21.44, P = 0.808).ConclusionA decrease in culprit lesion 2-[18F]FDG-uptake 3 months after an event indicates a decrease in inflammatory activity, suggesting that carotid plaque stabilization over time. 3D ultrasound morphological quantitative differences in GSM were not detectable after 3 months.

Introduction of the Grayscale Median for Ultrasound Tissue Characterization of the Transplanted Kidney.

Ultrasound examination is advised for early post-kidney transplant assessment. Grayscale median (GSM) quantification is novel in the kidney transplant field, with no systematic assessment previously reported. In this prospective cohort study, we measured the post-operative GSM in a large cohort of adult kidney transplant recipients (KTR) who consecutively underwent Doppler ultrasound directly after transplantation (within 24 h), compared it with GSM in nontransplanted patients, and investigated its association with baseline and follow-up characteristics. B-mode images were used to calculate the GSM in KTR and compared with GSM data in nontransplanted patients, as simulated from summary statistics of the literature using a Mersenne twister algorithm. The association of GSM with baseline and 1-year follow-up characteristics were studied by means of linear regression analyses. In 282 KTR (54 ± 15 years old, 60% male), the median (IQR) GSM was 55 (45–69), ranging from 22 to 124 (coefficient of variation = 7.4%), without differences by type of donation (p = 0.28). GSM in KTR was significantly higher than in nontransplanted patients (p < 0.001), and associated with systolic blood pressure, history of cardiovascular disease, and donor age (std. β = 0.12, −0.20, and 0.13, respectively; p < 0.05 for all). Higher early post-kidney transplant GSM was not associated with 1-year post-kidney transplant function parameters (e.g., measured and estimated glomerular filtration rate). The data provided in this study could be used as first step for further research on the application of early postoperative ultrasound in KTR.

Doppler Ultrasound Monitoring of Echogenicity in Asymptomatic Subcritical Carotid Stenosis and Assessment of Response to Oral Supplementation of Vitamin K2 (PLAK2 Randomized Controlled Trial).

Background: Plaque composition may predict the evolution of carotid artery stenosis rather than its sole extent. The grey scale median (GSM) value is a reproducible and standardized value to report plaque echogenicity as an indirect measure of its composition. We monitored plaque composition in asymptomatic subcritical carotid stenosis and evaluated the effect of an oral modulating calcification factor (vitamin K2). Methods: Carotid plaque composition was assessed by GSM value. Monitoring the effects of standard therapy (acetylsalicylic acid and low–medium dosage statin) (acetylsalicylic acid (ASA) arm) or standard therapy plus vitamins K2 oral supplementation (ASA + K2 arm) over a 12 months period was conducted using an ultrasound scan in a prospective, open-label, randomized controlled trial (PLAK2). Results: Sixty patients on low–medium dosage statin therapy were enrolled and randomized (30 per arm) to either ASA + K2 or ASA alone. Thirty-seven patients (61.6%) showed at 12 months a stable plaque with a mean increase in the GSM value in respect to the baseline of 2.6% with no differences between the two study arms (p = 0.66). Fifteen patients (25%) showed an 8% GSM value reduction respect the baseline with no differences between the two study arms (p = 0.99). At multivariable analysis, the adjusted mean (95% confidence interval) GSM change per month from baseline was greater in the ASA + K2 arm (−0.55 points, p = 0.048) compared to ASA alone (−0.18 points, p = 0.529). Conclusions: Carotid plaque composition monitoring through GSM value represents a laborious procedure. Although its use may not be applied to everyday practice, a specific application consists in evaluating the effect of pharmacological therapy on plaque composition. This 12 months randomized trial showed that the majority of subcritical asymptomatic carotid plaque on treatment with low–medium dosage statin presented a stable or increased echogenicity. Although vitamin K2 beyond standard therapy did not determine a significant change in plaque composition, for those who presented with GSM reduction it did enhance a GSM monthly decline.

Ultrasound-based internal carotid artery plaque characterization using deep learning paradigm on a supercomputer: a cardiovascular disease/stroke risk assessment system.

Visual or manual characterization and classification of atherosclerotic plaque lesions are tedious, error-prone, and time-consuming. The purpose of this study is to develop and design an automated carotid plaque characterization and classification system into binary classes, namely symptomatic and asymptomatic types via the deep learning (DL) framework implemented on a supercomputer. We hypothesize that on ultrasound images, symptomatic carotid plaques have (a) a low grayscale median because of a histologically large lipid core and relatively little collagen and calcium, and (b) a higher chaotic (heterogeneous) grayscale distribution due to the composition. The methodology consisted of building a DL model of Artificial Intelligence (called Atheromatic 2.0, AtheroPoint, CA, USA) that used a classic convolution neural network consisting of 13 layers and implemented on a supercomputer. The DL model used a cross-validation protocol for estimating the classification accuracy (ACC) and area-under-the-curve (AUC). A sample of 346 carotid ultrasound-based delineated plaques were used (196 symptomatic and 150 asymptomatic, mean age 69.9 ± 7.8years, with 39% females). This was augmented using geometric transformation yielding 2312 plaques (1191 symptomatic and 1120 asymptomatic plaques). K10 (90% training and 10% testing) cross-validation DL protocol was implemented and showed an (i) accuracy and (ii) AUC without and with augmentation of 86.17%, 0.86 (p-value < 0.0001), and 89.7%, 0.91 (p-value < 0.0001), respectively. The DL characterization system consisted of validation of the two hypotheses: (a) mean feature strength (MFS) and (b) Mandelbrot's fractal dimension (FD) for measuring chaotic behavior. We demonstrated that both MFS and FD were higher in symptomatic plaques compared to asymptomatic plaques by 64.15 ± 0.73% (p-value < 0.0001) and 6 ± 0.13% (p-value < 0.0001), respectively. The benchmarking results show that DL with augmentation (ACC: 89.7%, AUC: 0.91 (p-value < 0.0001)) is superior to previously published machine learning (ACC: 83.7%) by 6.0%. The Atheromatic runs the test patient in < 2s. Deep learning can be a useful tool for carotid ultrasound-based characterization and classification of symptomatic and asymptomatic plaques.

Optical coherence tomography and plaque morphology for revascularization of the superficial femoral artery.

The optical coherence tomography (OCT) catheter, Ocelot (Avinger Inc., Redwood City, CA), has been utilized to cross Trans-Atlantic Inter-Society Consensus Document (TASC) D lesions. Studies have assessed the characteristics of high-risk plaques in the carotid artery, but few, if any data exist evaluating OCT and plaque morphology in the superficial femoral artery (SFA). This study assessed SFA plaque morphology using OCT and lesion crossing success in chronic total occlusions (CTOs). We reviewed patients who underwent attempted infrainguinal revascularization with TASC D CTOs using the Ocelot catheter between June 2014 and June 2018, and recorded demographic information, smoking status, and medical comorbidities. A matched cohort of 44 successfully crossed lesions was compared to 44 that failed; images insufficient for analysis were excluded. The morphology of the plaque was studied using OCT at the proximal cap, midpoint of the lesion, and the distal cap. Morphologic data studied included the intima-media thickness ratio, cross-sectional area of the plaque, and gray-scale median of the plaque. A total of 140 patients who underwent lower extremity procedures for TASC D lesions of the SFA with OCT imaging were reviewed with a crossing rate of 69.0%. No significant differences were found between crossed and uncrossed lesions for intima-media thickness or cross-sectional area at the proximal cap, the midpoint, or the distal cap. A lower gray-scale median at the proximal cap was associated with the ability to cross the chronic SFA occlusion (P=0.05). Subgroup analysis stratified by smoking and calcium content also demonstrated that a lower gray-scale median at the proximal cap was associated with the ability to cross the chronic SFA occlusion (P=0.01 and P=0.04, respectively). Lower gray-scale median at the proximal cap of a chronic SFA occlusion calculated using OCT images was associated with the ability to successfully cross the lesion. Higher plaque gray-scale median is correlated with increased calcium, greater fibrous tissue, and signal-rich plaques. Gray-scale median in the proximal cap is useful marker to determine plaque composition and subsequent technical success for crossing chronic SFA occlusions. Further studies are needed to fully determine the utility of OCT images to predict successful endovascular revascularization of chronic SFA occlusions.

Proposal for computer-aided diagnosis based on ultrasound images of the kidney: is it possible to compare shades of gray among such images?

ObjectiveTo compare ultrasound images of the kidney obtained, randomly or in a controlled manner (standardizing the physical aspects of the ultrasound system), by various professionals and with different devices.Materials and MethodsWe evaluated a total of 919 images of kidneys, obtained by five professionals using two types of ultrasound systems, in 24 patients. The images were categorized into four types, by how they were acquired and processed. We compared the gray-scale median and different gray-scale ranges representative of virtual histological tissues.ResultsThere were statistically significant differences among the five professionals, regardless of the type of ultrasound system employed, in terms of the gray-scale medians for the images obtained (p < 2.2e-16). Analyzing the four categories of images-a totally random image (without any standardization); a standardized image (with fixed values for gain, time gain control, and dynamic range); a normalized version of the random image; and a normalized version of the standardized image-we determined that the random image, even after normalization, differed quite significantly among the professionals (p = 0.006098). The analysis of the normalized version of the standardized image did not differ significantly among the professionals (p = 0.7319).ConclusionOur findings indicate that a gray-scale analysis of ultrasound images of the kidney performs better when the image acquisition process is standardized and the images undergo a process of normalization.

Ultrasound-Based Carotid Plaque Characteristics Help Predict New Cerebral Ischemic Lesions after Endarterectomy

The aim of this study was to identify the ultrasound-based carotid plaque characteristics associated with new cerebral ischemic lesions after carotid endarterectomy (CEA). Between January 2013 and December 2018, carotid duplex ultrasound was performed in 1061 patients who underwent CEA. Brain magnetic resonance diffusion-weighted imaging (DWI) was performed pre-operatively and within 30 d after CEA. New cerebral ischemic lesions on DWI were observed in 169 patients. The cutoff value gray-scale median (GSM) used to distinguish DWI-positive from DWI-negative patients was 30.5, with an area under the receiver operating characteristic curve of 0.837. A larger proportion of multiple DWI lesions were observed in the GSM ≤30.5 group (59.5% vs. 41.5%, p = 0.030). Univariate and multivariate analyses identified GSM ≤30.5, ulcerated carotid plaques and pre-operative ischemic symptoms as predictors of post-operative cerebral DWI lesions. Our results indicate that ultrasound-based carotid plaque characteristics help predict new cerebral ischemic lesions after CEA.

Immunological analysis of carotid artery plaques and its relationship to the gray scale median value obtained by ultrasound

Abstract Introduction A gray scale median (GSM) value established by ultrasound could potentially reflect atherosclerotic plaque stability in carotid arteries, this stability could be also assessed by the measurements potential pro- and antiiflammatory characteristics of macrophages detected in the plaque. We analyzed association between the GSM value and several macrophage characteristics in carotid artery plaques. Methods Twenty-four patients (14 men, mean age 66.4±4.4 years) underwent ultrasound scan to determine the GSM value in maximum of one day before carotid endarterectomy. Immediately after removal, atherosclerotic plaques were processed for and analyzed by flow cytometric analysis. CD14, CD16, CD36, CD163 and CD206 markers were used to evaluate macrophage polarization. Results The GSM value ranged from 0 to 146. The majority of macrophages were established as CD14+CD16+. These macrophages also often co-expressed CD206, CD36 and CD163 while the expression of CD206 and CD36 in CD14+CD16- cells was lower and the expression of CD163 was almost negligible. Pro- and antiiflammatory macrophage phenotypes based on combination of different expression of CD markers did not correlate with the GSM value. In addition, no significant relationship was found between the GSM value and the presence of traditional cardiovascular risk factors. In patients with history of diabetes mellitus significantly lower percentage of CD14+CD16+CD206- macrophages was observed than in non.diabetics (p&amp;lt;0.05). Conclusion The GSM value did not correlate with potential pro- and antiiflammatory macrophage phenotypes. In addition, in contrast to published data, no relationship was found between the GSM value and the presence of cardiovascular risk factors Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Supported by Ministry of Health, Czech Republic - conceptual development of research organization; Thanks to courtesy of professor Andrew Nicolaides we used software developed by him and his colleagues to assess structure of carotid plaques by ultrasound.

An increase in activated NKT-CD8+ cells is associated with the presence of hypoechoic carotid plaques

Abstract Background The role of NK-cells and NKT-cells and their subtypes at various stages of the development of atherosclerosis is poorly understood. It was previously shown that CD3+CD56+CD8+ cells can secrete pro-inflammatory cytokines and an increase in their number has been established in patients with active Behçet's Disease and Multiple Sclerosis. Purpose To study the relationship between the number of activated CD3+CD56+CD8+ cells and the echogenicity of plaques in patients with carotid atherosclerosis. Methods The study included 40 patients, 21 (52.5%) men and 19 (47.5%) women who underwent carotid ultrasound and immunological studies. The median age was 53.5 (46.7; 57.0) years. All patients underwent duplex ultrasound scanning of the carotid arteries. If an atherosclerotic plaque was detected, its image was saved and exported to Adobe Photoshop CS6® followed by analysis of the gray-scale median (GSM) of the plaque. Hypoechoic was considered a carotid plaque whose GSM values were less than 50. The number of CD3+CD56+CD8+CD11b+ cells was evaluated by flow cytometry using a flow cytometer. Results Among the examined patients, carotid plaques were detected in 31 (77.5%) participants. The average values of GSM visualized plaques were 58.0 (46.0; 71.5). Atherosclerotic plaques with GSM &amp;lt;50 were detected in 11 (35.5%) patients. In patients with hypoechoic carotid plaques, the number of CD3+CD56+CD8+CD11b+ cells was statistically significantly higher – 352 (55.0; 505) cells/uL versus 66.0 (15.5; 138) cells/uL in patients with plaques whose GSM values were more than 50 (p=0.020). Based on the results of correlation analysis it was established inverse relationship between number of CD3+CD56+CD8+CD11b+ cells and GSM of plaques (r=−0.427; p=0.016). According to the results of the ROC-analysis, an increase in the number of activated NKT-CD8+ cells over 46.5 cells/uL was a predictor of the presence of hypoechogenic carotid plaques with a sensitivity of 81.8% and a specificity of 45.0% (see Figure 1). Conclusion In patients with hypoechoic carotid plaques, the number of CD3+CD56+CD8+CD11b+ cells was significantly higher in comparison with other patients. An increase in the number of activated NKT-CD8+ cells over 46.5 cells/uL was a predictor of the presence of hypoechoic carotid plaques with sensitivity of 81.8% and specificity of 45.0% Figure 1 Funding Acknowledgement Type of funding source: None

Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study: what have we learned from it?

The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study is the largest natural history study on patients with 50–99% asymptomatic carotid stenosis (ACS). It included 1,121 ACS individuals with a follow-up between 6 and 96 months (mean: 48 months). During the last 15 years, several important ACSRS substudies have been published that have contributed significantly to the optimal management of ACS patients. These studies have demonstrated that specific baseline clinical characteristics and ultrasonic plaque features after image normalization (namely carotid plaque type, gray scale median, carotid plaque area, juxtaluminal black area without a visible echogenic cup, discrete white areas in an echolucent part of a plaque, silent embolic infarcts on brain computed tomography scans, a history of contralateral transient ischemic attacks/strokes) can independently predict future ipsilateral cerebrovascular events. The ACSRS study provided proof that by use of a computer program to normalize plaque images and extract plaque texture features, a combination of features can stratify patients into various categories depending on their stroke risk. The present review will discuss the various reported predictors of future ipsilateral cerebrovascular events and how these characteristics can be used to calculate individual stroke risk.

Acupuncture treatment for carotid atherosclerotic plaques: study protocol for a pilot randomized, single blinded, controlled clinical trial

BackgroundCarotid atherosclerosis disease (CAD) is generally associated with the occurrence of cardiovascular and cerebrovascular accidents. However, CAD has not been taken seriously enough in the clinic, which, coupled with the single treatment and prevention of CAD, has led to a generally low level of patient compliance. Therefore, acupuncture is expected to be a safe and effective therapy that can be maintained in the long term for patients with CAD. The study objective is to evaluate the efficiency and reliability of acupuncture to relieve CAD and provide a new therapeutic idea for the clinical treatment of CAD.MethodsThis is a three-arm randomized clinical trial in China. Three groups (TA, SA, and MC) will be randomly allocated at a 1:1:1 ratio. The study will enrol 105 cervical atherosclerosis plaque patients in total on a voluntary basis, with 35 patients in each group. The treatment will last for 12 weeks, with two treatments per week for twenty-four treatments in total.ResultsTwo 3D ultrasound indicators will be measured as the primary outcomes: the total plaque volume (PV) of the carotid artery on each side and the grey-scale median (GSM). The secondary outcomes will include intima-media thickness (IMT), lipid levels, apolipoprotein A-IV level, platelet count (PLT), fibrinogen (FIB), and platelet aggregation rate (PAR). All the outcomes will be assessed before treatment, after treatment, and after a 12-week follow-up period. This study will utilize per-protocol (PP) and intention-to-treat (ITT) analysis principles.ConclusionsThis trial is to evaluate the efficacy and reliability of acupuncture in relieving carotid atherosclerotic plaques by establishing acupuncture (TA), sham acupuncture (SA), and medication (MC) groups.Ethics and disseminationThis study was approved by the Institutional Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (no. YF2018-107-01). All data and findings will be provided by the principal investigator via email.Trial registrationChiCTR, ChiCTR1800019259. Registered on 1 November 2018—retrospectively registered, http://www.chictr.org.cn/index.aspx

Association between periodontal disease and vulnerable plaque morphology in patients undergoing carotid endarterectomy.

Periodontal disease (PD) is a chronic inflammatory oral condition with potentially important systemic sequelae. We sought to determine whether the presence of PD in patients with severe carotid disease was associated with morphological features consistent with carotid plaque instability. A total of 52 dentate patients hospitalized for carotid endarterectomy (CEA) had standardized assessments of their periodontal status, including measurements of probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP). Carotid plaque morphology was assessed by ultrasound using the gray scale median (GSM) score and by immunohistochemistry using anti-CD68 and anti-alpha-actin antibodies, markers for macrophages and smooth muscle cells (SMCs) respectively. In total 30/52 patients (58%) had PD. Significant associations were noted between low GSM on ultrasound and each mm in PPD (p=0.001), each mm in CAL (p=0.002) and with a 10% increase in BoP (p=0.009). Using the standardized PERIO definition the association remained robust (aOR=10.4 [95% CI:2.3-46.3], p=.002). Significant associations were also observed with high macrophage accumulation and each individual PD measure (p<0.01 for PPD, CAL and BoP) and with the PERIO definition (aOR=15 [95% CI:1.8-127.8], p=.01). Similarly, low SMC density was also significantly associated with individual measures of PD (p<0.05 for PPD, CAL and BoP), but not with the PERIO definition (aOR 3.4 [95% CI:0.9-12.8], p=.07). The presence of PD was significantly associated with both ultrasound and immunohistochemistry features of carotid plaque instability in patients undergoing CEA.

Contrast enhanced ultrasound of carotid plaque in acute ischemic stroke (CUSCAS study).

Carotid atherosclerosis represents 8 to 15% of ischemic strokes in relation to the concept of "vulnerable" plaque. Contrast enhanced ultrasound (CEUS) can detect moving microbubbles within the plaque corresponding to neovessels that constitute "precursors" of vulnerable plaque and intraplaque hemorrhage. CEUS was not studied specifically in acute ischemic strokes. The aim of this study is to analyse the prevalence of CEUS carotid plaque ipsilateral at the ischemic stroke as well as the main characteristics of contrast-plaques. A single-centre prospective pilot study involving 33 consecutive patients with a stroke ≤10 days, diagnosed by an MRI with positive diffusion sequence and having a carotid plaque thickness ≥2.5mm with low or heterogeneous echogenicity, located in the ipsilateral carotid territory at the stroke. Plaque echogenicity was done by visual analysis and by measurement of the gray scale median (GSM). A transcranial Doppler monitoring was carried out in search of HITS. The contrast ultrasound was performed after 2.5 cc IV injection of SonoVue®. A video clip was recorded after injection which was used for interpretation by visual analysis in 3 grades, provided by two independent expert readers. The population consisted of 10 women and 23 men aged 73 on average. The topography of strokes in the carotid territory was located on the right in 11 (33%) cases and on the left in 22 (67%) cases. Seventeen patients had carotid stenosis between 0 and 49% according to the Nascet method and 16 patients had stenosis of 50 to 99%. The visual characterisation of the plaques had echolucent dominance (Type 1-2) in 18 cases and echogenic dominance (Type 3-4a) in 15 cases. Cardiovascular risk factors were common with no difference by sex. The inter-observer agreement of plaque enhancement was moderate in first reading (k=0.48) and excellent at consensus (k=0.91). Only one disagreement was found. Contrast agent enhancement of carotid plaque was observed in 11/32 patients, representing a prevalence of 34.4% - CI95% [17.9-50.9]. Variables associated with contrast plaque included the absence of antiplatelet drug (63.6% vs. 23.8%, P=0.05) and the presence of a regular edge on the plaque (91% vs. 48%, P=0.04). There was no difference in contrast enhancement for stenosis>or<50% in diameter and neither for the type of plaque. In a consecutive cohort of 33 patients, the prevalence of CEUS from an ipsilateral carotid plaque to a recent acute ischemic stroke was 34.4%. There was a statistically significant association between the contrast enhancement of the plaque and the absence of antiplatelet drug (P=0.05) and also the presence of a regular edge on the plaque (P=0.04). There was no correlation between plaque contrast and clinical and biological characteristics of patients or the presence of HITS.

Cardiovascular/stroke risk prevention: A new machine learning framework integrating carotid ultrasound image-based phenotypes and its harmonics with conventional risk factors

MotivationMachine learning (ML)-based stroke risk stratification systems have typically focused on conventional risk factors (CRF) (AtheroRisk-conventional). Besides CRF, carotid ultrasound image phenotypes (CUSIP) have shown to be powerful phenotypes risk stratification. This is the first ML study of its kind that integrates CUSIP and CRF for risk stratification (AtheroRisk-integrated) and compares against AtheroRisk-conventional. MethodsTwo types of ML-based setups called (i) AtheroRisk-integrated and (ii) AtheroRisk-conventional were developed using random forest (RF) classifiers. AtheroRisk-conventional uses a feature set of 13 CRF such as age, gender, hemoglobin A1c, fasting blood sugar, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), a ratio of TC and HDL, hypertension, smoking, family history, triglyceride, and ultrasound-based carotid plaque score. AtheroRisk-integrated system uses the feature set of 38 features with a combination of 13 CRF and 25 CUSIP features (6 types of current CUSIP, 6 types of 10-year CUSIP, 12 types of quadratic CUSIP (harmonics), and age-adjusted grayscale median). Logistic regression approach was used to select the significant features on which the RF classifier was trained. The performance of both ML systems was evaluated by area-under-the-curve (AUC) statistics computed using a leave-one-out cross-validation protocol. ResultsLeft and right common carotid arteries of 202 Japanese patients were retrospectively examined to obtain 404 ultrasound scans. RF classifier showed higher improvement in AUC (~57%) for leave-one-out cross-validation protocol. Using RF classifier, AUC statistics for AtheroRisk-integrated system was higher (AUC = 0.99,p-value<0.001) compared to AtheroRisk-conventional (AUC = 0.63,p-value<0.001). ConclusionThe AtheroRisk-integrated ML system outperforms the AtheroRisk-conventional ML system using RF classifier.

Echolucent carotid plaque is associated with restenosis after carotid endarterectomy.

The mechanism of carotid endarterectomy (CEA) restenosis remains unclear. Our research aimed to investigate the relationship between the carotid plaque grayscale median (GSM) value and restenosis after CEA. Between January 2010 and January 2018, 1280 consecutive patients underwent CEA at our institution; 32 patients were diagnosed with restenosis by ultrasound at 1 year after CEA. The correlations between plaque GSM, plaque echogenicity, clinical manifestations, shunting, and restenosis were analyzed. In total, 829 patients were ultimately enrolled; 32 (4%) presented diagnoses of restenosis (mean age 67.3 ± 8.0 years, 81.2% men). The GSM value was lower in the restenosis group (68.1 ± 19.9 vs 59.9 ± 14.7, p = 0.02). After multiple logistic regression analysis, the GSM value was found to be an independent risk factor for restenosis (OR 0.976, 95% CI 0.957-0.995). Shunting was another significant independent risk factor for restenosis (OR 2.39, 95% CI 1.07-5.34). The GSM cutoff value for predicting restenosis was 75 (sensitivity 0.38, specificity 0.84, area under the curve 0.62). We separated the patients into 2 groups by GSM (GSM ≤ 75 and GSM > 75 subgroups). Comparison of the 2 groups indicated that symptomatic manifestation was related to restenosis in the subgroup with GSM ≤ 75, indicating predominantly echolucent plaques, but not in the subgroup with GSM > 75, indicating predominantly echogenic plaques. Predominantly echolucent carotid plaques, as measured by GSM, had a higher restenosis risk at 1 year than echogenic plaques.

P173 Progression of subclinical cardiovascular disease in SLE: a five year follow up study

Abstract Background Patients with SLE have 5-10-fold increased risk of developing CVD compared to age and sex-matched controls. The average age of developing a first CVD event in patients with SLE is only 49. In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline. Methods We carried out vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD at baseline. Sixty-nine patients were rescanned over a median of 5 years of follow up. Ninety-four percent who were re-scanned were women and the mean overall age was 46 years (SD 11). Clinical and CVD risk was assessed at baseline and follow up. The same protocol for assessment at baseline using B-mode Doppler ultrasound to measure intimal media thickness and plaque was used at follow up to assess progression. We also assessed total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM) which is linked to plaque lipid content. Results Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p &amp;lt; 0.01) and common carotid IMT (0.065 vs 0.055, p &amp;lt; 0.01) were significantly raised in plaque vs non-plaque patients. In a multi -variable analysis CIMT at follow-up was independently associated with age (beta 0.415, p &amp;lt; 0.001) and diastolic blood pressure (beta 0.285, p &amp;lt; 0.021). Independent predictors of plaque at follow-up scan on multi-variable analysis were age at scan&amp;gt;52 years (OR 10.41, CI 2.66-40.80) and systolic BP &amp;gt; 133 (OR 5.26, CI 1.396 - 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta = -1.167, p = 0.002) and with GSM (beta = -0.513, p = 0.012). Conclusion Amongst these 69 patients, 26% had increased plaque and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE. Disclosures J. Bakshi: None. M. Griffin: None. S. Croca: None. F. Farhina: None. D. Isenberg: None. A. Nicolaides: None. A. Rahman: None.

Ultrasound risk marker variability in symptomatic carotid plaque: impact on risk reclassification and association with temporal variation pattern

PurposeUltrasound examinations of atherosclerotic carotid plaques can be used to calculate risk markers associated with plaque vulnerability. Recent studies demonstrate significant inter-frame variability in risk markers. Here, we investigate risk marker variability in symptomatic plaques and its impact on reclassification of plaque vulnerability, as well as its association with the shape of the temporal variation over the cardiac cycle.Methods56 patients with symptomatic carotid stenosis were included in this study. 88 plaques were identified and the plaque risk markers size (area), echogenicity (gray scale median, GSM) and heterogeneity (coarseness) were measured in all frames of ultrasound B-mode image sequences. Inter-frame variability was quantified using the coefficient of variation (CV).ResultsInter-frame variabilities of the risk markers were area CV 5–8%; GSM CV 4–7%; coarseness CV 8–15% and was in general significantly lower in large as compared to smaller plaques. The variability in GSM risk marker caused a reclassification of vulnerability in 30 to 38% of the plaques. Temporal variations in GSM with a heart rate periodic or drift/trending pattern were found in smaller plaques (< 26 mm2), whereas random pattern was found in larger plaques. In addition, hypoechoic plaques (GSM < 25) were associated with cyclic variation pattern, independent of their size.ConclusionsRisk marker variability causes substantial reclassification of plaque vulnerability in symptomatic patients. Inter-frame variation and its temporal pattern should be considered in the design of future studies related to risk markers.

Abstract MP09: Effect of Estradiol Therapy on Arterial Wall Echomorphology in the Early versus Late Intervention Trial With Estradiol(elite)

Objective: The effect of estradiol therapy (ET) has been evaluated on atherosclerosis progression measured by carotid artery wall thickness. Echogenicity of the arterial wall, a measure of lipid deposition, has not been investigated in relation to ET. Methods: This is a secondary analysis from ELITE. A total of 643 healthy postmenopausal women were randomized within time-since-menopause strata (early (&lt;6 years) and late (&gt;10 years) postmenopause) to daily 1 mg estradiol or placebo. The atherosclerosis outcome for the current analysis is grey scale median (GSM, unitless), a qualitative measure of atherosclerosis based on echogenicity obtained by high resolution ultrasonography of the common carotid arterial wall. Lower GSM values indicate more lipid deposition. GSM and serum concentrations of estradiol (E2) were assessed every 6 months over a median 5-year trial period. Linear mixed effects regression models were used to compare the rate of GSM progression between the randomized groups within time-since-menopause strata. The association of mean on-trial serum E2 levels with GSM progression was also tested using similar mixed effects model. Results: The effect of ET on the annual rate of GSM progression significantly differed between early and late postmenopause strata (p-value for interaction = 0.006). Annual GSM progression rate (95% confidence interval) among women in early postmenopause decreased by -0.30 (-0.63, 0.04) per year among women taking ET compared to -1.41 (-1.77, -1.06) per year among the placebo group (p&lt;0.0001). In contrast, the annual GSM progression rate was not significantly different between ET and placebo among the late postmenopausal women (p=0.37). The positive association between mean on-trial E2 level (pg/ml) and GSM progression rate was stronger and significant among early postmenopausal women (0.008 (0.0007, 0.016)) compared to women in the late postmenopause group (0.003 (-0.006, 0.01)). However, this differential association between E2 level and GSM progression rate was not statistically significant (p-value for interaction = 0.33). Conclusion: Compared to placebo, oral ET significantly reduced progression of lipid deposition in the carotid arterial wall among women in early postmenopause. ET had no such beneficial effect in late postmenopause. Associations between serum estradiol levels and lipid deposition validated those findings. Qualitative assessment of subclinical atherosclerosis (GSM) complements the anatomic assessment by carotid artery intima-media thickness.