title: Increased neovascularization in advanced lipid-rich atherosclerotic lesions detected by gadofluorine-M-enhanced MRI: implications for plaque vulnerability.
abstract: BACKGROUND
  Inflammation and neovascularization may play a significant role in atherosclerotic plaque progression and rupture. We evaluated gadofluorine-M-enhanced MRI for detection of plaque inflammation and neovascularization in an animal model of atherosclerosis.
  
  
  RESULTS
  Sixteen rabbits with aortic plaque and 6 normal control rabbits underwent gadofluorine-M-enhanced MRI. Eight rabbits had advanced atherosclerotic lesions, whereas the remaining 8 had early lesions. Magnetic resonance atherosclerotic plaque enhancement was meticulously compared with plaque inflammation and neovessel density as assessed by histopathology. Advanced plaques and early atheroma were enhanced after gadofluorine-M injection. Control animals displayed no enhancement. After accounting for the within-animal correlation of observations, mean contrast-to-noise ratio was significantly higher in advanced plaques than compared with early atheroma (4.29+/-0.21 versus 3.00+/-0.32; P=0.004). Macrophage density was higher in advanced plaques in comparison to early atheroma (geometric mean=0.50 [95% CI, 0.19 to 1.03] versus 0.25 [0.07 to 0.42]; P=0.05). Furthermore, higher neovessel density was observed in advanced plaques (1.83 [95% CI, 1.51 to 2.21] versus 1.29 [0.99 to 1.69]; P=0.05). The plaque accumulation of gadofluorine-M correlated with increased neovessel density as shown by linear regression analysis (r=0.67; P<0.001). Confocal and fluorescence microscopy revealed colocalization of gadofluorine-M with plaque areas containing a high density of neovessels.
  
  
  CONCLUSIONS
  Gadofluorine-M-enhanced MRI is effective for in vivo detection of atherosclerotic plaque inflammation and neovascularization in an animal model of atherosclerosis. These findings suggest that gadofluorine-M enhancement reflects the presence of high-risk plaque features believed to be associated with plaque rupture. Gadofluorine-M plaque enhancement may therefore provide functional assessment of atherosclerotic plaque in vivo.
authors.affiliation: Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris 7-Denis Diderot, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sirol
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Moreno
authors.forename: K-Raman
authors.initials: KR
authors.lastname: Purushothaman
authors.forename: Esad
authors.initials: E
authors.lastname: Vucic
authors.forename: Vardan
authors.initials: V
authors.lastname: Amirbekian
authors.forename: Hanns-Joachim
authors.initials: HJ
authors.lastname: Weinmann
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D003287:Contrast Media; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005466:Fluorocarbons; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D016014:Linear Models; D050356:Lipid Metabolism; D008264:Macrophages / Q000473:pathology; D018810:Magnetic Resonance Angiography; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D009942:Organometallic Compounds; D011237:Predictive Value of Tests; D011817:Rabbits; D015203:Reproducibility of Results; D012421:Rupture
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D009942:Organometallic Compounds; C517961:gadofluorine M