title: Early identification of aortic valve sclerosis using iron oxide enhanced MRI.
abstract: OBJECTIVE
  To test the ability of MION-47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS).
  
  
  METHODS
  The aortic valves of control and cholesterol-fed New Zealand White rabbits were imaged in vivo pre- and 48 h post-intravenous administration of MION-47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION-47 aortic valve cusps were imaged ex vivo on a 3.0T whole-body MR system with a custom gradient insert coil and a three-dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol-fed contrast-free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake.
  
  
  RESULTS
  MION-47 enhanced the visibility of both control and cholesterol-fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast-administered aortic valves. Signal voids were not observed in contrast-free valve cusps. In MION-47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol-fed valves but also in myofibroblasts from control and cholesterol-fed valves.
  
  
  CONCLUSIONS
  Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage-specific iron compound rather than passive targeting may be required.
authors.affiliation: Department of Anatomy, The University of Western Ontario, London, ON, Canada.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Hamilton
authors.forename: Kem A
authors.initials: KA
authors.lastname: Rogers
authors.forename: Andre J L
authors.initials: AJ
authors.lastname: Belisle
authors.forename: John A
authors.initials: JA
authors.lastname: Ronald
authors.forename: Brian K
authors.initials: BK
authors.lastname: Rutt
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Derek R
authors.initials: DR
authors.lastname: Boughner
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000175:diagnosis*; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053758:Nanoparticles; D011817:Rabbits; D012598:Sclerosis; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; C499827:monocrystalline iron oxide nanoparticle; D052203:Ferrosoferric Oxide