Linking Carotid Plaque Immune Subtypes to Multimodal Ultrasound Features
Yue Liu1, Shuang Yang1, Ying Wang1
1Department of Ultrasound, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China (Y.L., S.Y., Y.W., Y.H., X.L.).
Rationale And Objectives:
To establish a plaque immune microenvironment classification system and explore whether multimodal ultrasound may aid in the non-invasive identification of high-risk subtypes.This exploratory study investigated the association between PCA-derived immune subtypes and multimodal ultrasound features.
Methods:
This prospective study included 50 patients undergoing carotid endarterectomy (CEA). Seven immunohistochemistry (IHC) markers: interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-2, cluster of differentiation 11b (CD11b), myeloperoxidase (MPO), and microvessel density (MVD) were assessed. Principal component analysis (PCA) and hierarchical clustering defined immune subtypes. Preoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) evaluated vulnerability score, plaque thickness, and intraplaque neovascularization (IPN) grade.
Results:
Hierarchical clustering revealed three functional modules: core pro-inflammatory (TNF-α, IL-6, IL-2, IFN-γ), angiogenesis-macrophage (CD11b, MVD), and MPO-alone. PCA classified 50 plaques into four subtypes: Type I (inflammation-dominated, n=8), Type II (angiogenesis-dominated, n=14), Type III (high inflammation and high angiogenesis, n=11), and Type IV (stable, n=17). Type III plaques had highest inflammatory factors and MVD, with 45.5% experiencing recent ischemic events. Ultrasound vulnerability score correlated with IL-6 (r=0.54) and MVD (r=0.52); IPN grade correlated strongly with MVD (r=0.69). Type III showed a "high-risk triad": high vulnerability score (median 5.0), increased thickness (0.45 cm), and high IPN grade (45.5% grade 3). Type II had isolated high IPN grade (71.4% ≥ grade 2).
Conclusion:
PCA-based immune subtyping of carotid plaques appears feasible. Multimodal ultrasound, particularly vulnerability score and IPN grade, may aid in the non-invasive identification of high-risk subtypes, suggesting a potential imaging strategy for plaque risk stratification.
