Early identification of aortic valve sclerosis using iron oxide enhanced MRI.
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.
Hamilton
Amanda M
AM
Department of Anatomy, The University of Western Ontario, London, ON, Canada.
Rogers
Kem A
KA
Belisle
Andre J L
AJ
Ronald
John A
JA
Rutt
Brian K
BK
Weissleder
Ralph
R
Boughner
Derek R
DR
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
D003287:Contrast Media; C499827:monocrystalline iron oxide nanoparticle; D052203:Ferrosoferric Oxide