title: Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta: relationship between signal loss and macrophage infiltration.
abstract: OBJECTIVE
  Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10-enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits.
  
  
  RESULTS
  Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10-induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r=0.82; P<0.05).
  
  
  CONCLUSIONS
  Ferumoxtran-10-enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.
authors.affiliation: INSERM U698, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Hyafil
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Laissy
authors.forename: Mikael
authors.initials: M
authors.lastname: Mazighi
authors.forename: Didier
authors.initials: D
authors.lastname: Tchétché
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chillon
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Feldman
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000293:injuries / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects*; D017364:Collagenases / Q000378:metabolism; D003287:Contrast Media / Q000494:pharmacology*; D003911:Dextrans; D004792:Enzyme Precursors / Q000378:metabolism; D052203:Ferrosoferric Oxide; D018093:Gelatinases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000276:immunology / Q000473:pathology*; D007501:Iron / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D011817:Rabbits; D014657:Vasculitis / Q000276:immunology / Q000473:pathology
chemical_list: D003287:Contrast Media; D003911:Dextrans; D004792:Enzyme Precursors; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020780:Matrix Metalloproteinase 9; D052203:Ferrosoferric Oxide