title: Investigating vulnerable atheroma using combined (18)F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation.
abstract: Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy.
  
  
  METHODS
  Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression.
  
  
  RESULTS
  The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density.
  
  
  CONCLUSIONS
  We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.
authors: Institute of Nuclear Medicine, University College London, London, UK.
authors: Leon J
authors: LJ
authors: Menezes
authors: Carl W
authors: CW
authors: Kotze
authors: Obi
authors: O
authors: Agu
authors: Toby
authors: T
authors: Richards
authors: Jocelyn
authors: J
authors: Brookes
authors: Vicky J
authors: VJ
authors: Goh
authors: Manuel
authors: M
authors: Rodriguez-Justo
authors: Raymondo
authors: R
authors: Endozo
authors: Richard
authors: R
authors: Harvey
authors: Syed W
authors: SW
authors: Yusuf
authors: Peter J
authors: PJ
authors: Ell
authors: Ashley M
authors: AM
authors: Groves
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001681:Biological Assay; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000601:surgery; D016894:Endarterectomy, Carotid; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D064847:Multimodal Imaging; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000473:pathology*; D049268:Positron-Emission Tomography; D012044:Regression Analysis; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019788:Fluorodeoxyglucose F18; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule