Noninvasive Detection of Macrophage-Rich Atherosclerotic Plaque in Hyperlipidemic Rabbits Using "Positive Contrast" Magnetic Resonance Imaging

Grigorios Korosoglou, Robert George Weiss, Dorota Kedziorek, Piotr Walczak, Wesley D. Gilson, Michael Schar, David E. Sosnovik, Dara Kraitchman, Raymond C. Boston, Jeff W Bulte, Ralph Weissleder, Matthias Stuber

Research output: Contribution to journalArticle

Abstract

Objectives: 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 μmol 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.

Original languageEnglish (US)
Pages (from-to)483-491
Number of pages9
JournalJournal of the American College of Cardiology
Volume52
Issue number6
DOIs
StatePublished - Aug 5 2008

Fingerprint

Atherosclerotic Plaques
Macrophages
Magnetic Resonance Imaging
Rabbits
Nanoparticles
Iron
Atherosclerosis
Histology
Sequence Inversion
Area Under Curve
Rupture
Coronary Vessels
Thrombosis
Magnetic Resonance Spectroscopy
Myocardial Infarction
Confidence Intervals
Injections
Water

Keywords

  • atherosclerosis {black small square} vulnerable plaque {black small square} superparamagnetic nanoparticles {black small square} molecular imaging {black small square} inversion recovery with ON-resonant water suppression

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Noninvasive Detection of Macrophage-Rich Atherosclerotic Plaque in Hyperlipidemic Rabbits Using "Positive Contrast" Magnetic Resonance Imaging. / Korosoglou, Grigorios; Weiss, Robert George; Kedziorek, Dorota; Walczak, Piotr; Gilson, Wesley D.; Schar, Michael; Sosnovik, David E.; Kraitchman, Dara; Boston, Raymond C.; Bulte, Jeff W; Weissleder, Ralph; Stuber, Matthias.

In: Journal of the American College of Cardiology, Vol. 52, No. 6, 05.08.2008, p. 483-491.

Research output: Contribution to journalArticle

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abstract = "Objectives: 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 μmol 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.",
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AU - Korosoglou, Grigorios

AU - Weiss, Robert George

AU - Kedziorek, Dorota

AU - Walczak, Piotr

AU - Gilson, Wesley D.

AU - Schar, Michael

AU - Sosnovik, David E.

AU - Kraitchman, Dara

AU - Boston, Raymond C.

AU - Bulte, Jeff W

AU - Weissleder, Ralph

AU - Stuber, Matthias

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N2 - Objectives: 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 μmol 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.

AB - Objectives: 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 μmol 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.

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