Correlations With Coronary Plaque Histological Vulnerability and Physiological Environment

BACKGROUND 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque. OBJECTIVES This prospective study aimed to evaluate the associations between in vivo coronary 18F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary 18F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of 18F-NaF adsorption to vascular microcalcification.METHODS Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and 18F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary 18F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor -a, interleukin-1b), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High-and low-to medium-risk plaques were defined by standard pathological classification.RESULTS A total of 55 specimens were obtained from 42 CAD patients. Coronary 18F-NaF activity of high-risk specimens was significantly higher than low-to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary 18F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histolog-ically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor -a expression, and interleukin-1b expression correlated with coronary18F-NaF activity (all P < 0.05). No significant association between coronary 18F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05).CONCLUSIONS Coronary 18F-NaF activity was associated with histological vulnerability, CD68 expression, inflamma-tory cytokines expression, but not with osteogenic differentiation cytokines expression. 18F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients. (J Am Coll Cardiol Img 2023;16:508-520) (c) 2023 by the American College of Cardiology Foundation.