Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque.
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 100mumol/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.
te Boekhorst
Bernard C M
BC
Department of Cardiology, University Medical Center Utrecht, The Netherlands. b.c.m.teboekhorst@umcutrecht.nl
Bovens
Sandra M
SM
Nederhoff
Marcel G J
MG
van de Kolk
Kees W A
KW
Cramer
Maarten J M
MJ
van Oosterhout
Matthijs F M
MF
Ten Hove
Michiel
M
Doevendans
Pieter A
PA
Pasterkamp
Gerard
G
van Echteld
Cees J A
CJ
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans / Q000493:pharmacokinetics; D005188:False Negative Reactions; D052203:Ferrosoferric Oxide / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency
D001057:Apolipoproteins E; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D052250:Nitric Oxide Synthase Type III; D052203:Ferrosoferric Oxide