Plaque-Level Machine Learning Prediction of Intraplaque Hemorrhage in Carotid Arteries Using Computed Tomography Angiography.

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Abstract

Carotid artery plaques, especially those with intraplaque hemorrhage (IPH), are significant contributors to ischemic stroke. Although high-resolution magnetic resonance vessel-wall imaging (HR-MR-VWI) is the gold standard for assessing plaque vulnerability, its limited availability and high cost pose challenges. Computed tomography angiography (CTA) offers a more accessible, non-invasive alternative, but its ability to detect IPH and assess plaque instability remains underexplored. Machine learning techniques have shown promise in improving the prediction of carotid plaque vulnerability using CTA. This study aimed to develop and validate a machine learning model using CTA to predict IPH in carotid plaques. The model integrated key imaging features, including plaque composition, vascular lumen geometry, and perivascular adipose tissue (PVAT), with HR-MR-VWI serving as the reference standard. The goal was to evaluate the model's potential for non-invasive plaque vulnerability prediction, particularly in clinical settings where MRI is not available. A retrospective analysis was conducted on patients who underwent both carotid CTA and HR-MR-VWI within one month. Key plaque features, including composition, vascular lumen geometry, and PVAT, were extracted from CTA. The dataset was split into training (70%) and validation (30%) sets. Feature selection was performed using LASSO regression, followed by model development with logistic regression, random forest, XGBoost, and support vector machine (SVM). Hyperparameter tuning was performed using 10-fold cross-validation. Model performance was assessed using AUC, ROC curves, calibration curves, precision-recall curves, and confusion matrices. SHAP analysis was employed to evaluate the importance of each feature. In the validation cohort, the Random Forest model achieved an AUC of 0.679, sensitivity of 86.0%, specificity of 45.6%, accuracy of 63.0%, positive predictive value (PPV) of 54.4%, and negative predictive value (NPV) of 81.2%. Feature selection using LASSO regression identified perivascular adipose tissue (PVAT) attenuation, maximum diameter stenosis (MDS), and fibrotic volume (FV) as the most important predictors. SHAP analysis confirmed MDS as the most influential feature, followed by FV and PVAT. The model demonstrated good calibration, with predicted probabilities aligning closely with observed outcomes. Decision Curve Analysis (DCA) showed that the Random Forest model provided the highest net benefit at higher decision thresholds, supporting its clinical potential for predicting plaque vulnerability. This study demonstrates the potential of a CTA-based machine learning model for predicting carotid plaque vulnerability, with PVAT, MDS, and FV as key predictors. While the model shows good sensitivity, its moderate specificity suggests the need for further refinement, particularly by incorporating additional clinical and morphological data. Given its high sensitivity and negative predictive value, this model is positioned as a non-invasive screening and triage tool to identify patients who may benefit from subsequent HR-MR-VWI, rather than a standalone definitive diagnostic classifier. Future research should focus on multi-center validation and the integration of clinical data to improve accuracy and clinical applicability.

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