Noninvasive Assessment of Carotid Plaques Calcification by 18F-Sodium Fluoride Accumulation: Correlation with Pathology

Abstract

Vascular calcification is currently recognized as an important pathobiological process in atherosclerosis, but the mechanism remains elusive. Given the similarities in vascular calcification and bone formation, 18F-sodium fluoride (18F-NaF) is now considered a novel marker of vascular calcification. This study aimed to correlate 18F-NaF accumulation with the histological characterization of vascular calcification in carotid plaques. A total of 8 patients who were undergoing carotid endarterectomy (CEA) for carotid artery stenosis were recruited. Before CEA, 18F-NaF positron emission tomography and computed tomography (PET-CT) studies were conducted. 18F-NaF uptake was measured by the maximum standardized uptake value and the target-to-background ratio. The Hounsfield unit (HU) value was also measured. Postoperative carotid plaques were investigated by hematoxylin and eosin staining, alizarin red staining, and immunohistochemistry (alpha-smooth muscle actin and CD68). 18F-NaF uptake was observed in the bilateral carotid bifurcation of all patients. Compared with the pathology results, there was a significant correlation between tracer activity in the carotid plaques and the calcification in the corresponding histological sections (integrated optical density [IOD]: r = .781, P = .022; positive area: r = .765, P = .027). A negative correlation was observed between 18F-NaF uptake and smooth muscle cell staining (IOD: r = -.710, P = .049). 18F-NaF uptake did not correlate with carotid artery stenosis, HU value, or inflammation. 18F-NaF PET-CT is a noninvasive imaging method for the assessment of calcification in human carotid atherosclerotic plaques and a promising approach to studying calcification in atherosclerotic lesions.