Ultrasound-Based Precision Assessment and Intervention of Vulnerable Atherosclerotic Plaques: From Plaque Characterization to Therapeutic Modulation

Abstract Luminal stenosis remains central to clinical decision-making but does not fully characterize the plaque features associated with instability and embolization. This narrative review examines the progression from ultrasound-based plaque characterization to therapeutic modulation, with carotid atherosclerosis as the principal clinical focus. Contrast-enhanced ultrasound (CEUS) has the strongest human evidence among advanced methods for microvascular plaque characterization, linking intraplaque enhancement with histologic neovascularization and symptomatic disease. Superb microvascular imaging, elastography, and ultrasound localization microscopy provide complementary measures of slow flow, tissue mechanics, and microvascular architecture. Molecular ultrasound has visualized endothelial activation, platelet deposition, and angiogenic targets in animal models; studies of human endarterectomy specimens have confirmed the expression and accessibility of several candidate vascular targets ex vivo. Experimental nanoscale probes also target foam-cell lipids and extracellular matrix within plaque. Ultrasound-targeted delivery and sonodynamic therapy (SDT) modify macrophages, matrix, and neovessels in experimental plaques. A randomized SDT trial in femoropopliteal disease reported reduced plaque inflammation and improved walking performance; small carotid or mixed-territory studies report imaging responses. Carotid stroke-prevention benefit remains to be established. Serial ultrasound measurements during lipid-lowering treatment provide a human application of imaging-based response assessment.