Carotid Plaque [¹⁸F]FDG PET in Symptomatic Carotid Disease: A Narrative Review of Prognostic Evidence and Clinical Translation

Abstract

Carotid atherosclerosis remains a major preventable cause of ischemic stroke, yet risk assessment based primarily on luminal stenosis may overlook biologically active, nonstenosing plaques. This limitation is increasingly important given the substantial global stroke burden and the large proportion of ischemic strokes without an identified cause. This review evaluates whether [¹⁸F]fluorodeoxyglucose positron-emission tomography ([¹⁸F]FDG PET) can address this gap by imaging inflammation-related glucose metabolism within carotid plaques. Preclinical and histopathologic studies associate increased FDG uptake with macrophage-rich inflammation, hypoxia, plaque vulnerability, and treatment response, while prospective clinical studies link higher uptake to early and long-term recurrent ipsilateral stroke independently of stenosis severity. The discussion examines the biological basis and quantification of FDG uptake, mechanisms of plaque instability and cerebral ischemia, human validation and prognostic evidence, integration with stenosis measurement, plaque morphology, vessel-wall magnetic resonance imaging (MRI), and the Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, and comparison with [¹⁸F]sodium fluoride PET ([¹⁸F]NaF PET) imaging of active microcalcification. However, FDG uptake is neither cell-specific nor a direct marker of plaque rupture or intraplaque hemorrhage, and the existing evidence is limited by heterogeneous imaging protocols, small and overlapping cohorts, limited external validation, and an emphasis on recently symptomatic disease. Accordingly, [¹⁸F]FDG PET should currently be regarded as an adjunctive research biomarker rather than a standalone basis for revascularization. Standardized imaging methods, independent prospective validation in asymptomatic and nonstenosing disease, and randomized trials of PET-guided management are needed to determine whether molecular plaque imaging can improve treatment selection and prevent stroke.