***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World . Preventive measures , however , often fail and cardiovascular disease may manifest as an acute coronary syndrome , stroke or even sudden death after years of silent progression . Thus , there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases . During the past 10 years , several retrospective and prospect i ve clinical studies have been published using 18F-fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) to quantify inflammation in atherosclerotic plaques . However , the current variety of imaging protocol s used for vascular ( arterial ) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries . Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine ( EANM ) Cardiovascular Committee , the objective of this position paper was to propose optimized and st and ardized protocol s for imaging and interpretation of PET scans in atherosclerosis . These recommendations do not , however , replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocol s used and the individual patient , in consultation with the patient and , where appropriate and necessary , the patient ’s guardian or carer . These recommendations suffer from the absence of conclusive evidence on many of the recommendations . Therefore , they are not intended and should not be used as " strict guidelines " but should , as already mentioned , provide a basis for st and ardized clinical atherosclerosis  PET imaging protocol s , which are subject to further and continuing evaluation and improvement . However , this EANM position paper might indeed be a first step towards " official " guidelines on atherosclerosis imaging with PET Objectives This study assessed 5 frequently applied arterial 18fluorodeoxyglucose ( 18F-FDG ) uptake metrics in healthy control subjects , those with risk factors and patients with cardiovascular disease ( CVD ) , to derive uptake thresholds in each subject group . Additionally , we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies . Background 18F-FDG positron emission tomography ( PET ) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials . However , an overview of 18F-FDG uptake metrics , threshold values , and reproducibility in healthy compared with diseased subjects is not available . Methods 18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects ( 61 ± 8 years ) comprising 3 groups : 25 healthy controls , 23 patients at increased CVD risk , and 35 patients with known CVD . We quantified  18F-FDG uptake across the whole artery , the most-diseased segment , and within all active segments over several pre-defined cutoffs . We report these data with and without background corrections . Finally , we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results . Results All 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta . Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio ( TBR ) value ( TBRmax ) ; whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta . These were exceeded by > 52 % of risk factor patients and > 67 % of CVD patients . Reproducibility was excellent in all study groups ( intraclass correlation coefficient > 0.95 ) . Using carotid TBRmax as a primary endpoint result ed in sample size estimates approximately 20 % lower than aorta . Conclusions We report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects , which are exceeded by the majority of CVD patients . This remains true , independent of readout vessel , signal quantification method , or the use of background correction . We also confirm the high reproducibility of 18F-FDG PET measures of inflammation . Nevertheless , because of overlap between subject categories and the relatively small population studied , these data have limited generalizability until substantiated in larger , prospect i ve event-driven studies . ( Vascular Inflammation in Patients at Risk for Atherosclerotic Disease ; NTR5006 Background and Purpose — Carotid endarterectomy is currently guided by angiographic appearance on the assumption that the most stenotic lesion visible at angiography is likely to be the lesion from which future embolic events will arise . However , risk of plaque rupture , the most common cause of atherosclerosis-related thromboembolism , is dictated by the composition of the plaque , in particular the degree of inflammation . Angiography may , therefore , be an unreliable method of identifying vulnerable plaques . In this study , plaque inflammation was quantified before endarterectomy using the combination of 18F fluorodeoxyglucose positron (FDG)-emission tomography ( PET ) and high-resolution MRI ( HRMRI ) . Methods — Twelve patients , all of whom had suffered a recent transient ischemic attack , had a severe stenosis in the ipsilateral carotid artery , and were awaiting carotid endarterectomy underwent FDG-PET and HRMRI scanning .  A semiquantitative estimate of plaque inflammation was calculated for all of the lesions identified on HRMRI . Results — In 7 of 12 patients ( 58 % ) , high FDG uptake was seen in the lesion targeted for endarterectomy . In the remaining 5 patients , FDG uptake in the targeted lesion was low . In these 5 patients , 3 had nonstenotic lesions identified on HRMRI that exhibited a high level of FDG uptake . All 3 of the highly inflamed nonstenotic lesions were located in a vascular territory compatible with the patients ’ presenting symptoms . Conclusions — Our data suggest that angiography may not always identify the culprit lesion . Combined FDG-PET and HRMRI can assess the degree of inflammation in stenotic and nonstenotic plaques and could potentially be used to identify lesions responsible for embolic events BACKGROUND The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease . We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ( (18)F-NaF ) and (18)F-fluorodeoxyglucose ( (18)F-FDG ) . METHODS In this prospect i ve clinical trial , patients with myocardial infa rct ion ( n=40 ) and stable angina ( n=40 ) underwent (18)F-NaF and (18)F-FDG PET-CT , and invasive coronary angiography . (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease , and with intravascular ultrasound in patients with stable angina . The primary endpoint was the comparison of (18)F-fluoride tissue-to- background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infa rct ion . FINDINGS In 37 ( 93 % ) patients with myocardial infa rct ion , the highest coronary (18)F-NaF uptake was seen in the culprit plaque ( median maximum tissue-to- background ratio : culprit 1·66 [ IQR 1·40 - 2·25 ] vs highest non-culprit 1·24 [ 1·06 - 1·38 ] , p<0·0001 ) . By contrast , coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible , there were no differences between culprit and non-culprit plaques ( 1·71 [ 1·40 - 2·13 ] vs 1·58 [ 1·28 - 2·01 ] , p=0·34 ) . Marked  (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification , macrophage infiltration , apoptosis , and necrosis . 18 ( 45 % ) patients with stable angina had plaques with focal (18)F-NaF uptake ( maximum tissue-to- background ratio 1·90 [ IQR 1·61 - 2·17 ] ) that were associated with more high-risk features on intravascular ultrasound than those without uptake : positive remodelling ( remodelling index 1·12 [ 1·09 - 1·19 ] vs 1·01 [ 0·94 - 1·06 ] ; p=0·0004 ) , microcalcification ( 73 % vs 21 % , p=0·002 ) , and necrotic core ( 25 % [ 21 - 29 ] vs 18 % [ 14 - 22 ] , p=0·001 ) . INTERPRETATION (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque . Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease . FUNDING Chief Scientist Office Scotl and and British Heart Foundation Background Inflammation drives atherosclerotic plaque rupture . Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ( [18F]FDG PET ) , [18F]FDG lacks cell specificity , and coronary imaging is unreliable because of myocardial spillover . Objectives This study tested the efficacy of gallium-68-labeled DOTATATE ( 68Ga-DOTATATE ) , a somatostatin receptor subtype-2 (SST2)-binding PET tracer , for imaging atherosclerotic inflammation . Methods We confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques . 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis . Results Target SSTR2 gene expression occurred exclusively in “ proinflammatory ” M1 macrophages , specific 68Ga-DOTATATE lig and binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions , and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals ( r = 0.89 ; 95 % confidence interval [ CI ] : 0.28 to 0.99 ; p = 0.02 ) . 68Ga-DOTATATE mean of maximum tissue-to-blood ratios ( mTBRmax ) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome ( median difference : 0.69 ; interquartile range [ IQR ] : 0.22 to 1.15 ; p = 0.008 ) and transient ischemic attack/stroke ( median difference : 0.13 ; IQR : 0.07 to 0.32 ; p = 0.003 ) . 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features ( receiver operating characteristics area under the curve [ ROC AUC ] : 0.86 ; 95 % CI : 0.80 to 0.92 ; p < 0.0001 ) , and correlated with Framingham risk score ( r = 0.53 ; 95 % CI : 0.32 to 0.69 ; p < 0.0001 ) and [18F]FDG uptake ( r = 0.73 ; 95 % CI : 0.64 to 0.81 ; p < 0.0001 ) . [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions ( median difference : 0.12 ; IQR : 0.0 to 0.23 ; p = 0.008 ) and high-risk from lower-risk coronary arteries ( ROC AUC : 0.76 ; 95 % CI : 0.62 to 0.91 ; p = 0.002 ) ; however , myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients ( 64 % ) . Coronary 68Ga-DOTATATE PET scans were readable in all patients . Conclusions We vali date d 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging , excellent macrophage specificity , and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG . ( Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [ VISION ] ; NCT02021188 It is known that risk of cerebrovascular accident is not only associated with degree of carotid artery stenosis 
    Output:
    
PET/CT using 18F-FDG can demonstrate carotid plaque inflammation , and is a marker of symptomatic disease .