Correlation Of Carotid Atherosclerotic Plaque Detected By Ultrasonography With Ischemic Cerebro-cardiovascular Events

Objective: This study aimed to investigate the clinical,conventional ultrasonography(US),contrast-enhanced ultrasonography(CEUS),and radiomic features of patients with carotid artery plaque,to evaluate the factors related to symptomatic plaque,future cerebrocardiovascular events in asymptomatic patients,future recurrent stroke in symptomatic patients and to evaluate the diagnostic performance of the nomogram.Methods: Patients with carotid artery plaque detected by US were enrolled in this study.A clinical and conventional US model of carotid plaque was generated using clinical and conventional US features.A radiomic model was generated based on radiomic features on US images.The clinical and conventional US model,radiomic model,and the final nomogram were used to identify symptomatic carotid plaque and predict future cerebrocardiovascular events and event-free survival(EFS)The diagnostic and predictive performance of the clinical and conventional US model,radiomic model and final nomogram were compared.The final nomograms were examined to improve the sonographer’s ability to predict cerebro-cardiovascular events and improve the risk stratification ability of the revised Framingham Stroke Risk Profile(r FSRP).Further,risk factors for recurrent stroke were determined.The contribution of risk factors to the Essen Stroke Risk Score(ESRS)was determined.Results: The US-based radiomics model and the final nomogram outperformed the clinical and conventional US models in identifying symptomatic carotid plaque(both P<0.05).The Concordance index(C-index)value of the final nomogram for predicting EFS increased significantly compared with those of the clinical and conventional US model and the USbased radiomics model(all P<0.05).The sensitivity and accuracy of the sonographers’ visual scores for predicting future cerebro-cardiovascular events were significantly improved using the final nomogram-assisted method(both P<0.05).The overall net reclassification improvement for adding the final nomogram to the r FSRP was 19.6%.The presence of carotid plaque with intraplaque neovascularization(IPN)grade 2 on CEUS was a significant and independent predictor of recurrent stroke.The overall net reclassification improvement for the addition of IPN grade on CEUS to the ESRS was 32.0%.Conclusions: The nomogram has a high diagnostic value for identification of symptomatic carotid plaque and prediction of future cerebro-cardiovascular events in asymptomatic patients,thereby improving the sensitivity and accuracy of sonographers’ visual scores for carotid plaque and the risk stratification ability of revised r FSRP.In addition,the presence of carotid plaque with IPN grade 2 on the CEUS was a significant and independent predictor of stroke recurrence in patients with ischemic stroke.The addition of IPN grade on CEUS improved the risk stratification capability of the ESRS.Part Ⅰ: Relation of clinical symptoms and carotid plaque features detected with ultrasonography-based radiomicsObjective: This study sought to develop a nomogram for identifying symptomatic carotid plaques using US-based radiomics and clinical and conventional US features.Methods: In this prospective study,548 patients(mean±standard deviation age,63±10 years;373 men)were enrolled and randomly divided into a training or test cohort.Clinical and conventional US features of carotid plaques were used to generate a clinical and conventional US model.A US-based radiomics model was constructed by extracting radiomics features from grayscale and strain elasticity images.Multivariate logistic regression was performed using radiomics scores and clinical and conventional US features,and a final nomogram was subsequently developed.The performance of the final nomogram was assessed for discrimination and clinical usefulness in the training and test cohorts and the CEUS test cohort.Results: Radiomics scores in all patients with symptomatic carotid plaques were significantly higher than those with asymptomatic carotid plaques(both P<0.05).The USbased radiomics model [area under the curve(AUC)=0.931 and 0.922 for the training and test cohorts,respectively] and final nomogram(AUC=0.927 and 0.916 for the training and test cohorts,respectively)outperformed the clinical and conventional US model(AUC=0.723 and 0.580 for the training and test cohorts,respectively,both P<0.05).The decision curve analysis revealed that the final nomogram was clinically useful.In patients who underwent CEUS,the prevalence of plaque enhancement was higher in high-risk patients than in low-risk patients,based on the final nomogram score(P=0.008).Conclusions: The nomogram has a high diagnostic performance for identifying symptomatic carotid plaques.Part Ⅱ: Prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques using ultrasonography radiomics-based nomogramObjective: This study aimed to develop a nomogram combining US-based radiomics,clinical and conventional US features to predict future cerebro-cardiovascular events,to optimize risk stratification in patients with asymptomatic carotid plaques,and to investigate the additional contribution of final nomogram to the r FSRP for cerebro-cardiovascular risk prediction.Methods: In this multi-institutional study of 2009 patients,we developed a nomogram combining US-based radiomics,clinical and conventional US features for predicting cerebro-cardiovascular events and EFS.The final nomogram’s prognostic accuracy,ability to improve the sonographers’ prediction of cerebro-cardiovascular events,and contribution to the r FSRP were assessed.Results: We generated the final nomogram using P<0.05 multivariate Cox regression variables(dyslipidemia,lumen diameter,plaque echogenicity,and US-based radiomics risk score).The C-index of the final nomogram for predicting EFS was 0.708 in the training cohort,0.632 in the internal validation cohort,0.574 in the external validation cohort 1,and 0.639 in the external validation cohort 2.The C-index of the final nomogram increased significantly compared with that of the clinical and conventional US and the US-based radiomics models in the training cohort,internal validation cohort,external validation cohort 1,and external validation cohort 2(all P<0.05).The sensitivity and accuracy of the sonographers’ visual scores for carotid plaque were significantly improved by the final nomogram-assisted method(both P<0.05).The overall net reclassification improvement for adding the final nomogram to the r FSRP was 19.6%.Conclusions: The final nomogram allowed accurate prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques and improved the sensitivity and accuracy of sonographers’ visual score for carotid plaque and the risk stratification ability of r FSRP.Part ⅠII: Value of intraplaque neovascularization on contrast-enhanced ultrasonography in predicting ischemic stroke recurrence in patients with carotid atherosclerotic plaqueObjective: This study sought to investigate the relationship between carotid plaque IPN grade on CEUS and future recurrent stroke and to establish whether IPN grade contributes to the risk assessment for recurrent stroke compared with the ESRS.Methods: This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaque at our hospital between August 2020 and December 2020.CEUS examination was performed within 30 days after stroke.130 patients were followed up for 15–27 months or until stroke recurrence was finally analyzed.IPN grade on CEUS was investigated as a possible risk factor for stroke recurrence and adjunct to ESRS.Results: During the follow-up,25 patients(19.2%)experienced a recurrent stroke.Patients with IPN grade 2 on CEUS had an increased risk of stroke recurrence events(22/73,30.1%)compared with patients with IPN grade 1 on CEUS(3/57,5.3%)with an adjusted hazard ratio(HR)of 38.264(95% confidence interval [CI]: 14.975–97.767;P< 0.001)according to multivariable Cox proportional hazards model analysis,indicating that the presence of carotid plaque with IPN grade 2 on CEUS was a significant,independent predictor of recurrent stroke.When the IPN grade on CEUS was added to the ESRS,the HR for stroke recurrence in the high-risk groups compared to the low-risk group(2.188 [95% CI: 0.025–3.388])was greater than that of ESRS alone(1.706;95% CI: 0.810–9.014).The overall net reclassification improvement for the addition of IPN grade on CEUS to the ESRS was 32.0%.Conclusions: The presence of carotid plaque with IPN grade 2 on CEUS was a significant and independent predictor of stroke recurrence in patients with ischemic stroke.Furthermore,the addition of IPN grade on CEUS improved the risk stratification capability of the ESRS.