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Predictive Value of 18F-Sodium Fluoride Positron Emission Tomography in Detecting High-Risk Coronary Artery Disease in Combination With Computed Tomography.

ABSTRACT: Background Application of 18F-sodium fluoride (18F-NaF) positron emission tomography ( PET ) to coronary artery disease has attracted interest. We investigated the utility of 18F-NaF uptake for predicting coronary events and evaluated the combined use of coronary computed tomography (CT) angiography ( CCTA ) and 18F-NaF PET /CT in coronary artery disease risk assessment. Methods and Results This study included patients with ?1 coronary atherosclerotic lesion detected on CCTA who underwent 18F-NaF PET / CT . High-risk plaque on CCTA was defined as plaque with low density (<30 Hounsfield units) and high remodeling index (>1.1). Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue:background ratio ( TBR max), and maximum TBR max per patient (M- TBR max) was determined. Thirty-two patients having a total of 112 analyzed lesions were followed for 2 years after 18F-NaF PET / CT scan, and 11 experienced coronary events (acute coronary syndrome and/or late coronary revascularization [after 3 months]). Patients with coronary events had higher M- TBR max than those without (1.39±0.18 versus 1.19±0.17, respectively; P=0.0034). The optimal M- TBR max cutoff to predict coronary events was 1.28 (area under curve: 0.79). Patients with M- TBR max ?1.28 had a higher risk of earlier coronary events than those with lower M- TBR max ( P=0.0062 by log-rank test). In patient-based (n=41) and lesion-based (n=143) analyses of CCTA findings that predicted higher coronary 18F-NaF uptake, the presence of high-risk plaque was a significant predictor of both M- TBR max ?1.28 and TBR max ?1.28. Conclusions 18F-NaF PET / CT has the potential to detect high-risk coronary artery disease and individual coronary lesions and to predict future coronary events when combined with CCTA . Clinical Trial Registration URL : www.umin.ac.jp . Unique identifier: UMIN 000013735.

SUBMITTER: Kitagawa T

PROVIDER: S-EPMC6474946 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Predictive Value of 18F-Sodium Fluoride Positron Emission Tomography in Detecting High-Risk Coronary Artery Disease in Combination With Computed Tomography.

Kitagawa Toshiro T Yamamoto Hideya H Nakamoto Yumiko Y Sasaki Ko K Toshimitsu Shinya S Tatsugami Fuminari F Awai Kazuo K Hirokawa Yutaka Y Kihara Yasuki Y

Journal of the American Heart Association 20181001 20

Background Application of 18F-sodium fluoride (18F-NaF) positron emission tomography ( PET ) to coronary artery disease has attracted interest. We investigated the utility of 18F-NaF uptake for predicting coronary events and evaluated the combined use of coronary computed tomography (CT) angiography ( CCTA ) and 18F-NaF PET /CT in coronary artery disease risk assessment. Methods and Results This study included patients with ≥1 coronary atherosclerotic ...[more]

PMID: 30371290

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Project description:BackgroundMicrocalcifications in atherosclerotic plaques are destabilizing, predict adverse cardiovascular events, and are associated with increased morbidity and mortality.18F-fluoride positron emission tomography (PET)/computed tomography (CT) imaging has demonstrated promise as a useful clinical diagnostic tool in identifying high-risk plaques; however, there is confusion as to the underlying mechanism of signal amplification seen in PET-positive, CT-negative image regions. This study tested the hypothesis that 18F-fluoride PET/CT can identify early microcalcifications.Methods18F-fluoride signal amplification derived from microcalcifications was validated against near-infrared fluorescence molecular imaging and histology using an in vitro 3-dimensional hydrogel collagen platform, ex vivo human specimens, and a mouse model of atherosclerosis.ResultsMicrocalcification size correlated inversely with collagen concentration. The 18F-fluoride ligand bound to microcalcifications formed by calcifying vascular smooth muscle cell derived extracellular vesicles in the in vitro 3-dimensional collagen system and exhibited an increasing signal with an increase in collagen concentration (0.25 mg/mL collagen -33.8×102±12.4×102 counts per minute; 0.5 mg/mL collagen -67.7×102±37.4×102 counts per minute; P=0.0014), suggesting amplification of the PET signal by smaller microcalcifications. We further incubated human atherosclerotic endarterectomy specimens with clinically relevant concentrations of 18F-fluoride. The 18F-fluoride ligand labeled microcalcifications in PET-positive, CT-negative regions of explanted human specimens as evidenced by 18F-fluoride PET/CT imaging, near-infrared fluorescence, and histological analysis. Additionally, the 18F-fluoride ligand identified micro and macrocalcifications in atherosclerotic aortas obtained from low-density lipoprotein receptor-deficient mice.ConclusionsOur results suggest that 18F-fluoride PET signal in PET-positive, CT-negative regions of human atherosclerotic plaques is the result of developing microcalcifications, and high surface area in regions of small microcalcifications may amplify PET signal.

Dataset Information

Predictive Value of 18F-Sodium Fluoride Positron Emission Tomography in Detecting High-Risk Coronary Artery Disease in Combination With Computed Tomography.

Publications

Predictive Value of <sup>18</sup>F-Sodium Fluoride Positron Emission Tomography in Detecting High-Risk Coronary Artery Disease in Combination With Computed Tomography.

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