Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque

Abstract Objective USPIOs are used clinically as contrast agent for magnetic resonance imaging (MRI) of lymph nodes, and in research settings for MRI of macrophages in atherosclerotic lesions. However, T2* weighted (T2*w) imaging can lead to “blooming” with overestimation of the area occupied by USP...

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Published in:Atherosclerosis 2010-05, Vol.210 (1), p.122-129
Main Authors: te Boekhorst, Bernard C.M, Bovens, Sandra M, Nederhoff, Marcel G.J, van de Kolk, Kees W.A, Cramer, Maarten J.M, van Oosterhout, Matthijs F.M, ten Hove, Michiel, Doevendans, Pieter A, Pasterkamp, Gerard, van Echteld, Cees J.A
Format: Article
Language:English
Subjects:
Animals
Aorta, Abdominal - metabolism
Apolipoproteins E - deficiency
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Atherosclerosis - pathology
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular
Cellular MRI
Contrast Media - pharmacokinetics
Coronary heart disease
Dextrans - pharmacokinetics
False Negative Reactions
Ferrosoferric Oxide - pharmacokinetics
Heart
Lymph nodes
Lymph Nodes - metabolism
Lymph Nodes - pathology
Magnetic Resonance Imaging
Magnetite Nanoparticles
Male
Medical sciences
Mice
Mice, Knockout
Nitric Oxide Synthase Type III - deficiency
USPIOs
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Summary:Abstract Objective USPIOs are used clinically as contrast agent for magnetic resonance imaging (MRI) of lymph nodes, and in research settings for MRI of macrophages in atherosclerotic lesions. However, T2* weighted (T2*w) imaging can lead to “blooming” with overestimation of the area occupied by USPIOs. In this study, plaque uptake of USPIOs in atherosclerotic mice was investigated in the presence and absence of circulating monocytes. The influence of peri-aortic lymph node uptake on the interpretation of T2*w images of the aortic wall was studied. Methods Atherosclerotic mice were fed an atherogenic diet and were randomized to total body irradiation or non-irradiation. After 2 days, T2*w MRI of the abdominal aorta was performed, followed by intravenous administration of 100 μmol/kg USPIOs ( t = 0). At t = 3 and 5 days MRI of the abdominal aorta was repeated. Animals were sacrificed and histological evidence for iron uptake by aortic wall and lymph nodes was compared with the degree of focal signal loss on in vivo MR images. Results Aortic walls in irradiated and non-irradiated mice, but also in healthy wild-type mice, showed signal loss on T2*w MRI. Signal loss however did not correspond with histological evidence of USPIO uptake by aortic wall but by peri-aortic lymph nodes. Conclusions The versatility of USPIOs as a negative MR contrast agent for both lymph node staging and atherosclerosis may limit the use for detection of atherosclerotic lesions in vessels where lymph nodes are highly prevalent.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2009.10.036