Linking Carotid Plaque Immune Subtypes to Multimodal Ultrasound Features

IF 4.7 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Academic Radiology Pub Date : 2026-10-01 Epub Date: 2026-08-06 DOI:10.1016/j.acra.2026.07.046
Yue Liu, Shuang Yang, Ying Wang, Yan Hu, Xiaoli Liu, Guangxiang Yang, Huanhuan Hao, Jianlin Wu
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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. 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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.
颈动脉斑块免疫亚型与多模态超声特征的联系
理由与目的:建立斑块免疫微环境分类系统,探讨多模态超声是否有助于高危亚型的无创识别。本探索性研究探讨了pca衍生免疫亚型与多模态超声特征之间的关系。方法:本前瞻性研究包括50例接受颈动脉内膜切除术(CEA)的患者。7项免疫组化(IHC)指标:白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、干扰素-γ (IFN-γ)、IL-2、分化聚类11b (CD11b)、髓过氧化物酶(MPO)、微血管密度(MVD)。主成分分析(PCA)和层次聚类定义了免疫亚型。术前常规超声和超声造影(CEUS)评估易损评分、斑块厚度和斑块内新生血管(IPN)等级。结果:分层聚类揭示了三个功能模块:核心促炎(TNF-α, IL-6, IL-2, IFN-γ),血管生成-巨噬细胞(CD11b, MVD)和mpo单独。PCA将50个斑块分为四种亚型:I型(炎症为主,n=8), II型(血管生成为主,n=14), III型(高炎症和高血管生成,n=11)和IV型(稳定,n=17)。III型斑块的炎症因子和MVD最高,45.5%的斑块近期经历过缺血事件。超声易损评分与IL-6 (r=0.54)、MVD (r=0.52)相关;IPN分级与MVD呈正相关(r=0.69)。III型表现为“高风险三联征”:高脆弱性评分(中位数5.0),厚度增加(0.45 cm),高IPN等级(45.5% 3级)。II型患者分离出高IPN分级(≥2级71.4%)。结论:基于pca的颈动脉斑块免疫分型是可行的。多模态超声,特别是易损性评分和IPN分级,可能有助于无创识别高风险亚型,提示斑块风险分层的潜在成像策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Academic Radiology
Academic Radiology 医学-核医学
CiteScore
7.60
自引率
10.40%
发文量
432
审稿时长
18 days
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.
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