Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques.

Abstract

New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.

• Authors: Claudio Vinegoni, Ion Botnaru, Elena Aikawa, Marcella A Calfon, Yoshiko Iwamoto, Eduardo J Folco, Vasilis Ntziachristos, Ralph Weissleder, Peter Libby, Farouc A Jaffer
• Journal: Science translational medicine (Sci Transl Med) Vol. 3 Issue 84 Pg. 84ra45 (May 25 2011) ISSN: 1946-6242 [Electronic] United States
• PMID: 21613624 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Lipoproteins, LDL
• Serum Albumin, Bovine
• Indocyanine Green

Topics

• Acetylation
• Animals
• Arteries (pathology, physiopathology)
• Capillary Permeability (physiology)
• Cattle
• Diagnostic Imaging (methods)
• Endocytosis
• Fluorescence
• Humans
• Indocyanine Green
• Inflammation (complications, pathology)
• Lipids (chemistry)
• Lipoproteins, LDL (metabolism)
• Macrophages (metabolism, pathology)
• Plaque, Atherosclerotic (complications, diagnosis, diagnostic imaging, physiopathology)
• Rabbits
• Radiography
• Serum Albumin, Bovine (metabolism)
• Spectroscopy, Near-Infrared (methods)