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Background and Aims: 18 F-Sodium Fluoride Positron Emission Tomography ( 18 F-NaF PET) non-invasively detects micro-calcification activity, the earliest stage of atherosclerotic arterial calcification. We studied the association between coronary 18 F-NaF uptake and high-risk plaque features on intra-coronary optical coherence tomography (OCT) and CT-angiography (CTCA) and the potential application to patient-level risk stratification., Methods: Sixty-two prospectively recruited patients with acute coronary syndrome (ACS) underwent multi-vessel OCT, 18 F-NaF PET and CTCA. The maximum tissue to background ratio (TBRmax = standardised uptake value (SUV)max/SUVbloodpool) was measured in each coronary segment on 18 F-NaF PET scans. High-risk plaque features on OCT and CTCA were compared in matched coronary segments. The number of patients testing positive (>2SD above the normal range) for micro-calcification activity was determined., Results: In 62 patients (age, mean ± standard deviation (SD) = 61 ± 9 years, 85% male) the coronary segments with elevated 18 F-NaF uptake had higher lipid arc (LA) (median [25th-75th centile]: 74° [35°-117°] versus 48° [15°-83°], p=0.021), higher prevalence of macrophages [n(%): 37 (62%) versus 89 (39%), p=0.008] and lower plaque free wall (PFW) (50° [7°-110°] versus 94° [34°-180°], p=0.027) on OCT, and a higher total plaque burden (p=0.011) and higher dense calcified plaque burden (p= 0.001) on CTCA, when compared with 18 F-NaF negative segments. Patients grouped by increasing number of coronary lesions positive for microcalcification activity (0,1, ≥2) showed decreasing plaque free wall, increasing calcification and increasing macrophages on OCT (respectively p=0.008, p < 0.001 and p=0.028)., Conclusions: 18 F-NaF uptake is associated with high-risk plaque features on OCT and CTCA in a per-segment and per-patient analysis in subjects hospitalized for ACS., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) remains a leading cause of death. Preventative therapies that reduce CVD are most effective when targeted to individuals at high risk. Current risk stratification tools have only modest prognostic capabilities, resulting in over-treatment of low-risk individuals and under-treatment of high-risk individuals. Improved methods of CVD risk stratification are required. Molecular imaging offers a novel approach to CVD risk stratification. In particular, 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) has shown promise in the detection of both high-risk atherosclerotic plaque features and vascular calcification activity, which predicts future development of new vascular calcium deposits. The rate of change of coronary calcium scores, measured by serial computed tomography scans over a 2-year period, is a strong predictor of CVD risk. Vascular calcification activity, as measured with 18 F-NaF PET, has the potential to provide prognostic information similar to consecutive coronary calcium scoring, with a single-time-point convenience. However, owing to the rapid motion and small size of the coronary arteries, new solutions are required to address the traditional limitations of PET imaging. Two different methods of coronary PET analysis have been independently proposed and here we compare their respective strengths, weaknesses, and the potential for clinical translation.