Advanced Ultrasound in Diagnosis and Therapy ›› 2026, Vol. 10 ›› Issue (4): 317-333.doi: 10.26599/AUDT.2026.260037
• REVIEW ARTICLE • Previous Articles Next Articles
Sun Yanga,*,1(
), Luo Wanga,b,1, Zhang Qunxiaa, Ren Jianlia, Wang Zhiganga, Ran Haitaoa,*(
)
Received:2026-09-14
Revised:2026-09-25
Accepted:2026-11-04
Online:2026-12-30
Published:2026-11-02
Contact:
Sun Yang, Ran Haitao,
E-mail:sunyang@cqmu.edu.cn;ranhaitao@cqmu.edu.cn
About author:First author contact:1Yang Sun and Wang Luo contributed equally to this study.
Sun Yang, Luo Wang, Zhang Qunxia, Ren Jianli, Wang Zhigang, Ran Haitao. Ultrasound-Based Precision Assessment and Intervention of Vulnerable Atherosclerotic Plaques: From Plaque Characterization to Therapeutic Modulation. Advanced Ultrasound in Diagnosis and Therapy, 2026, 10(4): 317-333.
Figure 1
Representative Doppler ultrasound appearances of carotid plaque. (A) Plaque with moderate echogenicity and a smooth surface; (B) Color-flow signals within the plaque region; (C) Plaque at the carotid bifurcation with a spectral Doppler trace; (D) Long-axis view of a plaque with sparse color-flow signals. Reproduced from Wang et al. [20]."
Table 1
Advanced ultrasound assessment of carotid plaque"
| Method | Primary quantity | Evidence | Key limitation | Role in plaque assessment |
| CEUS, contrast-enhanced ultrasound; IPN, intraplaque neovascularization; SMI, superb microvascular imaging; SWE, shear-wave elastography; ULM, ultrasound localization microscopy | ||||
| B-mode and duplex Doppler | Anatomy, burden, surface, stenosis, flow velocity | Established stenosis framework; structured morphology lexicon [ | Shadowing, plane dependence, scanner settings, and limited tissue specificity | Stenosis grading and structural description |
| 3D ultrasound and automated segmentation | Plaque volume and geometry | Histology/surgical-volume agreement and improved efficiency [ | Segmentation failure, registration drift, and uncertain outcome meaning of volume change | Quantification of burden; serial volume change as a research endpoint |
| CEUS | Intravascular enhancement and perfusion related to IPN | Histology correlation, symptom association, small prospective cohorts [ | Protocol and threshold heterogeneity; calcified plaques may be unevaluable; limited specificity for inflammation | Perfused neovessel assessment |
| SMI and related microvascular flow modes | Filtered low-velocity intraplaque flow | Agreement with CEUS and histologic neovessel density; pooled diagnostic studies [ | Vendor-specific clutter filtering and settings; signal differs from contrast kinetics | Noncontrast vascularity assessment within a defined scanner protocol |
| SWE and strain elastography | Stiffness or deformation | Histology studies and symptom-association meta-analysis [ | Pressure, cardiac phase, calcification, geometry, and reconstruction affect estimates | Regional mechanical characterization alongside plaque morphology |
| Ultrafast/vector-flow methods | Flow vectors and wall-shear-related indices | Small human surgical-validation and prospective technical cohorts [ | Boundary conditions, segmentation, and fitted composites | Characterization of local flow and loading |
| ULM | Super-resolved microvascular tracks, density, and velocity | Two small human feasibility/discrimination studies [ | Acquisition and processing dependence; outcome validation unavailable | Human feasibility mapping of microvascular architecture |
| AI/radiomics | Segmentation, quantification, feature integration, classification | Accurate volume measurement; high internal and emerging external discrimination [ | Patient leakage, vendor shift, and exclusion of calcified plaques | Measurement automation and research classification of plaque phenotypes |
Figure 2
Contrast-enhanced ultrasound (CEUS) and histologic neovascularization in human carotid plaque. (A) Color Doppler ultrasound at the carotid bifurcation; the red dashed contour marks the plaque; (B) CEUS of the same region, with focal intraplaque enhancement outlined by the yellow box; dashed lines connect this region to the corresponding histology in panel C; (C) Anti-CD31 immunohistochemistry from the corresponding plaque region; arrows identify CD31-positive neovessels, and the scale bar is 500 μm. Reproduced from Schmidt et al. [25]."
Figure 3
Standard carotid ultrasound and superb microvascular imaging (SMI) in community participants at high stroke risk. (A-F) show transverse and longitudinal views with limited intraplaque vascular signal (SMI grade 1); (G-L) show multiple short linear or strip-like signals in transverse and longitudinal views (SMI grade 2), marked by arrows in the source. Reproduced from Wang et al. [33]."
Figure 4
Ultrasound localization microscopy (ULM) density and velocity maps in three patients with histologically detected carotid plaque neovessels. (A, C, and E) show localized-bubble density; (B, D, and F) show the corresponding tracked-bubble velocity. Blue dashed contours are the source study's plaque segmentations. Adapted from Leroy et al. [34]."
Figure 5
Multiparametric assessment of the same human carotid plaque. (A) Shear-wave elastography, (B) B-mode ultrasound, (C) computed tomography angiography, and (D) gross endarterectomy specimen in longitudinal view. In the source, the red arrow marks a hemorrhagic region corresponding to low stiffness, low echogenicity, and low computed-tomography density; the white arrow marks a fibrous calcified region corresponding to high stiffness, high echogenicity, and high density. Ci, internal carotid artery; Cc, common carotid artery. Reproduced from Goudot et al. [38]."
Table 2
Evidence linking plaque imaging, treatment, and response assessment"
| Research area | Target or treatment | Measurements | Evidence | Unresolved clinical question |
| CEUS, contrast-enhanced ultrasound; EDB, extra-domain B; siRNA, small interfering RNA; SMI, superb microvascular imaging; UTMD, ultrasound-targeted microbubble destruction; VCAM-1, vascular cell adhesion molecule-1; vWF, von Willebrand factor. Human ex vivo evidence refers to excised plaque studies. Imaging responses and peripheral functional outcomes are distinct from carotid stroke-prevention outcomes | ||||
| Endothelial inflammation | Luminal VCAM-1 and P-selectin; experimental targeted microbubbles | Targeted molecular signal, target expression, and ex vivo agent binding | Animal molecular imaging and treatment-response studies [ | Can a clinical-grade agent measure carotid target engagement in vivo and inform treatment? |
| Platelet adhesion | Accessible vWF and activated platelet epitopes; experimental targeted microbubbles | Platelet/vWF-associated imaging signal and experimental treatment effects | Human ex vivo plaque target expression [ | How do timing and antiplatelet exposure affect signal interpretation and its relation to ipsilateral events? |
| Plaque-directed delivery | UTMD-assisted gene, antibody, siRNA, or drug delivery; EDB-fibronectin and other experimental targets | Payload delivery, target modulation, CEUS or stiffness, and histology | Animal delivery and imaging studies [ | What human dose, biodistribution, and repeat-treatment safety permit carotid application? |
| Sonodynamic therapy | Sensitizers and ultrasound in vascular or macrophage-rich experimental plaque | Vascular, inflammatory, and matrix changes; early clinical imaging and functional outcomes | Animal studies [ | Can carotid target engagement translate into durable benefit with acceptable neurological safety? |
| Treatment-response monitoring | Lipid-lowering or antithrombotic therapy | CEUS/SMI vascularity, plaque volume, and other ultrasound measurements | Human studies with treatment-related changes and neutral findings [ | Do imaging changes predict a reduction in stroke? |
Figure 6
Experimental molecular ultrasound with cyclic Arg-Gly-Asp-modified microbubbles (MBR) in mice. (A) Background-subtracted color-coded signal after MBR or control microbubbles (MBC) in C57BL/6 mice and ApoE−/− mice receiving a normal or high-cholesterol diet, with separate receptor-blocked groups; (B) Quantified video intensity (n = 6 per group); (C-F) Associations between MBR video intensity and endothelial or plaque glycoprotein IIb/IIIa, plaque vulnerability index, and necrotic-core/fibrous-cap ratio. Reproduced from Guo et al. [51]."
Figure 7
Plaque-directed delivery using platelet-membrane biomimetic rapamycin nanoparticles combined with ultrasound-targeted microbubble destruction (UTMD) in ApoE−/− mice. (A) Thirty-day treatment schedule; (B) En face Oil Red O-stained aortas; (C) Quantified aortic plaque area. Reproduced from Zhou et al. [65]."
Figure 8
Low-intensity focused-ultrasound-responsive nanoplatform for sonodynamic modulation of advanced rabbit femoral plaque. (A) Representative histopathology 28 days after treatment, including hematoxylin and eosin, CD31, Prussian blue, macrophage, Oil Red O, HIF-1α, Masson, smooth-muscle-cell, and endothelial staining. Red arrows in the source mark abnormal adventitial neovessels and white arrows mark intraplaque hemorrhage; (B-K) Quantification (n = 7; mean ± SD; analysis of variance with Dunnett post hoc comparisons as defined in the source). Reproduced from Yao et al. [70]."
Figure 9
Serial carotid ultrasound during lipid-lowering therapy in a prospective single-arm study. (A) Representative B-mode images at baseline and 6 months show little visible change in plaque morphology; (B) CEUS images and time–intensity curves from the same representative patient; (C, D) Cohort-level reductions in plaque-to-lumen area under the curve and enhanced-intensity ratios at 6 months; (E) Magnified plaque regions in the representative CEUS images; red arrows mark intraplaque vessels and blue arrows mark calcification in the source. Reproduced from Chen et al. [82]."
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