Molecular imaging of atherosclerotic plaque vulnerability: a narrative review

Atherosclerotic plaque rupture or erosion underlies most acute coronary and cerebrovascular events. Risk stratification currently relies on luminal stenosis, which poorly predicts thrombotic risk because many events arise from biologically vulnerable plaques with only mild-to-moderate narrowing. Molecular imaging enables non-invasive assessment of the biological processes that drive plaque instability. A structured narrative review of experimental and clinical studies published between 2000 and 2024 was conducted using PubMed and Ovid Embase. Searches related to atherosclerosis, vulnerable plaque, molecular imaging, inflammation, microcalcification, matrix remodelling, angiogenesis, and carotid or coronary disease identified 2,627 records, of which 38 studies were included after screening. Imaging of inflammation and microcalcification shows the greatest clinical maturity, primarily using positron emission tomography (PET). Inflammation is assessed with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), reflecting macrophage metabolic activity, while active microcalcification is detected with ¹⁸F-sodium fluoride (¹⁸F-NaF), which binds to hydroxyapatite in early calcific deposits. Imaging of fibrous cap degeneration and angiogenesis remains less clinically mature with limited human validation, including matrix metalloproteinase-targeted single-photon emission computed tomography (SPECT) and integrin-targeted magnetic resonance imaging (MRI) approaches. Translation is limited by technical complexity, cost, and scarce outcome-based validation. Molecular imaging provides biologically informed assessment of plaque vulnerability beyond stenosis alone. Imaging of inflammation and microcalcification currently show the greatest potential for risk stratification, although further validation and multimodal integration are required before routine clinical use.