{"title":"Linking Carotid Plaque Immune Subtypes to Multimodal Ultrasound Features","authors":"Yue Liu, Shuang Yang, Ying Wang, Yan Hu, Xiaoli Liu, Guangxiang Yang, Huanhuan Hao, Jianlin Wu","doi":"10.1016/j.acra.2026.07.046","DOIUrl":null,"url":null,"abstract":"<div><h3>Rationale and Objectives</h3><div>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.</div></div><div>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.</div><div><h3>Methods</h3><div>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.</div></div><div>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.</div><div><h3>Results</h3><div>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 (<em>r</em>=0.54) and MVD (<em>r</em>=0.52); IPN grade correlated strongly with MVD (<em>r</em>=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).</div></div><div>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 (<em>r</em>=0.54) and MVD (<em>r</em>=0.52); IPN grade correlated strongly with MVD (<em>r</em>=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).</div><div><h3>Conclusion</h3><div>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.</div></div><div>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.</div>","PeriodicalId":50928,"journal":{"name":"Academic Radiology","volume":"33 10","pages":"Pages 4668-4680"},"PeriodicalIF":4.7000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Academic Radiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1076633226005544","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/8/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.
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).
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.
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.
期刊介绍:
Academic Radiology publishes original reports of clinical and laboratory investigations in diagnostic imaging, the diagnostic use of radioactive isotopes, computed tomography, positron emission tomography, magnetic resonance imaging, ultrasound, digital subtraction angiography, image-guided interventions and related techniques. It also includes brief technical reports describing original observations, techniques, and instrumental developments; state-of-the-art reports on clinical issues, new technology and other topics of current medical importance; meta-analyses; scientific studies and opinions on radiologic education; and letters to the Editor.