Biomedical Engineering Reference
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lengths of the renal arteries, using MRA; this allowed an increase in the signal- to -
noise and contrast-to-noise ratios in the right coronary artery by an average of 80%
(p = 0.008) and 109% (p = 0.007), respectively [235]. Contrast agent AMI 227 has
also been used in MRA to visualize the aorta, the inferior vena cava, the portal
vein, and muscle in patients, with all blood vessels showing signifi cant enhance-
ment at 45 min after intravenous injection of the agent [236].
A further example of iron oxide nanoparticle-based blood pool contrast agent is
that of SHU 555, which has been used for chest MRA and cardiac perfusion. In
these studies, a clear dose-dependent increase in signal intensity was demon-
strated in the vessels, cardiac chambers and myocardium during both fi rst - pass
and equilibrium phases [237] .
4.5.1.7 Atherosclerosis Imaging
Many cardiovascular diseases, such as myocardial infarction, stroke, and periph-
eral vascular disease, are strongly related to atherosclerosis. Therefore, earlier
non-invasive imaging of atherosclerotic plaques is extremely important [238]. MRI
has great potential for the effective visualization and localization of plaques in the
vasculature, but current clinical studies involving MRI of atherosclerosis remain
few in number. Contrast agent-enhanced MRI of atherosclerosis is based on the
selective uptake of magnetic nanoparticles by macrophages in the macrophage-
rich atherosclerotic plaques. To date, only ferumoxtran-10 (Sinerem) has been
tested clinically in symptomatic patients scheduled for carotid endarterectomy.
The results of this study highlighted an accumulation of magnetic nanoparticles
in macrophages in predominantly ruptured and rupture-prone human atheroscle-
rotic lesions, which in turn caused a signal decrease (95%) in the in vivo MR
images after 24 h [239]. USPIO-enhanced MRI was also successfully utilized for
the noninvasive determination of macrophage burden in asymptomatic carotid
atheroma plaques [240, 241] .
4.5.2
Potential Clinical Applications
Much of the potential clinical research with these contrast agents involves in vitro
cellular imaging, the imaging of phantoms, and the in vivo imaging of animal
models. Targeted cellular labeling and molecular imaging represent the main
modern developments for the application of nanomaterials in MRI.
4.5.2.1 Cellular Labeling and Tracking
Today, research into stem cells and cell transplantation is a rapidly developing area
which is expected to result in important clinical applications. Typical subjects
include diagnostics and the treatment of spinal cord injury, Parkinson' s disease,
myelin disorders, Huntington's disease, and cardiovascular, renal and hepatic
diseases. MRI is currently one of the best techniques for tracking magnetically
labelled cells, as its resolution approaches the size of the cell itself [7]. In fact, MRI
can be used to visualize and track transplanted stem cells labelled with magnetic
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