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dc.contributor.authorvan, der Valk Fleur Men
dc.contributor.authorVerweij, Simone Len
dc.contributor.authorZwinderman, Koos AHen
dc.contributor.authorStrang, Aart Cen
dc.contributor.authorKaiser, Yen
dc.contributor.authorMarquering, Henk Aen
dc.contributor.authorNederveen, Aart Jen
dc.contributor.authorStroes, Erik SGen
dc.contributor.authorVerberne, Hein Jen
dc.contributor.authorRudd, Jamesen
dc.identifier.citationvan der Valk et al. JACC Cardiovascular Imaging (2016)en
dc.description.abstractObjectives: We assessed five 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 three 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 cut-offs. 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 TBR value; whole artery TBRmax 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 (ICC>0.95). Using carotid TBRmax as primary endpoint resulted 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 quantificantion 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, prospective event-driven studies.
dc.description.sponsorshipThis work was supported by a European Framework Program 7 grant (ESS: FP7-Health 309820: Nano-Athero). Erik Stroes has received lecturing fees from Merck, Novartis, ISIS, Amgen - none of are related to the contents of this manuscript. All other authors declare that they have no conflict of interest and no relationships with industry relevant to this study. JHFR is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation and the Wellcome Trust.
dc.rightsAttribution 4.0 International*
dc.subject18F-FDG PET/CTen
dc.titleThresholds for Arterial Wall Inflammation Quantified by 18F-Fluorodeoxyglucose Positron Emission Tomographic Imaging - Implications for Vascular Interventional Studiesen
dc.description.versionThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Elsevier.en
prism.publicationNameJACC Cardiovascular Imagingen
dc.rioxxterms.funderWellcome Trust
dc.contributor.orcidRudd, James [0000-0003-2243-3117]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (PG/09/083/27667)
pubs.funder-project-idBritish Heart Foundation (FS/12/29/29463)
cam.orpheus.successThu Jan 30 12:54:20 GMT 2020 - The item has an open VoR version.*

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International