Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging.
OBJECTIVE
This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]).


BACKGROUND
The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility.


METHODS
Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days.


RESULTS
After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis.


CONCLUSIONS
Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.
Korosoglou
Grigorios
G
Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Weiss
Robert G
RG
Kedziorek
Dorota A
DA
Walczak
Piotr
P
Gilson
Wesley D
WD
Schär
Michael
M
Sosnovik
David E
DE
Kraitchman
Dara L
DL
Boston
Raymond C
RC
Bulte
Jeff W M
JW
Weissleder
Ralph
R
Stuber
Matthias
M
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D006949:Hyperlipidemias / Q000150:complications*; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053758:Nanoparticles; D011817:Rabbits; D018570:Risk Assessment; D013923:Thromboembolism / Q000209:etiology*
D003287:Contrast Media; C499827:monocrystalline iron oxide nanoparticle; D052203:Ferrosoferric Oxide