title: Thresholds for Arterial Wall Inflammation Quantified by18F-FDG PET Imaging: Implications for Vascular Interventional Studies.
abstract: This study assessed 5 frequently applied arterial18fluorodeoxyglucose (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.
  
  
  
  18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available.
  
  
  
  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 quantified18F-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.
  
  
  
  All18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmaxis 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 TBRmaxas a primary endpoint resulted in sample size estimates approximately 20% lower than aorta.
  
  
  
  We report thresholds for physiological18F-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 of18F-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. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006).
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands. Electronic address: f.m.valkvander@amc.nl.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: van der Valk
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Simone L
authors.initials: SL
authors.lastname: Verweij
authors.affiliation: Department of Clinical Epidemiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Koos A H
authors.initials: KA
authors.lastname: Zwinderman
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Aart C
authors.initials: AC
authors.lastname: Strang
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Kaiser
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands; Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, the Netherlands; Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Henk A
authors.initials: HA
authors.lastname: Marquering
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
mesh_terms: D000368:Aged; D001011:Aorta / Q000000981:diagnostic imaging*; D001025:Aortitis / Q000000981:diagnostic imaging*; D001167:Arteritis / Q000000981:diagnostic imaging*; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D058226:Plaque, Atherosclerotic; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D015203:Reproducibility of Results
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: (18)F-FDG PET/CT; atherosclerosis; imaging; inflammation; thresholds