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Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits
S A Schmitz1, S E Coupland, R Gust
1Department of Radiology and Nuclear Medicine, Universitätsklinikum Benjamin Franklin, Berlin, Germany. s.schmitz@medizin.fu-berlin.de
Rationale And Objectives:
Inflammatory atherosclerotic plaques are characterized by increased endothelial permeability and multiple macrophages. Blood-pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammatory plaques. The objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by MRI and histology.
Methods:
Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T. Four groups of five animals each were studied: (1) without ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or 200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron stains.
Results:
Animals receiving 200 micromol Fe/kg demonstrated areas of focal signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P = 0.009). The number of images with this finding in groups 2 and 3 was not significantly different compared with controls. By microscopy, SPIO-iron was seen in the endothelial cells and subendothelial intimal macrophages of atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating iron uptake also showed a high macrophage content.
Conclusions:
SPIO accumulates in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques with increased endothelial permeability and a high macrophage content, two established features of plaque inflammation, it may have a potential for noninvasive assessment of inflammatory atherosclerotic plaques.
Insights
Superparamagnetic iron oxide (SPIO) accumulates in atherosclerotic plaques, detectable by MRI. This finding suggests SPIO
Area of Science:
- Biomedical Imaging
- Cardiovascular Research
- Nanotechnology
Background:
- Inflammatory atherosclerotic plaques exhibit increased endothelial permeability and macrophage infiltration.
- Superparamagnetic iron oxide (SPIO) nanoparticles target the monocyte-macrophage system.
- SPIO may serve as a contrast agent for labeling inflammatory plaques.
Purpose of the Study:
- To investigate SPIO uptake in atherosclerotic plaques in rabbits using MRI.
- To correlate MRI findings with histological evidence of SPIO deposition.
Main Methods:
- Watanabe hereditable hyperlipidemic rabbits underwent MRI at 1.5 T using a T2*-weighted sequence.
- Animals were divided into four groups, with three receiving varying doses and timings of SPIO (25 nm carboxydextran-coated) and one control group.
- In vivo MRI was compared with ex vivo histological iron staining.
Main Results:
- A dose of 200 micromol Fe/kg SPIO resulted in focal signal loss in the aortic wall in 31% of images, significantly different from controls (P = 0.009).
- Microscopy confirmed SPIO-iron within endothelial cells and macrophages in atherosclerotic lesions.
- Lesions with SPIO uptake showed a high macrophage content.
Conclusions:
- SPIO effectively accumulates in the aortic plaques of atherosclerotic rabbits.
- The MRI signal loss is a characteristic finding of SPIO deposition in plaques.
- SPIO's accumulation in plaques with high macrophage content and increased permeability suggests its potential for noninvasive assessment of inflammatory atherosclerotic plaques.