Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10

Area of Science:

• Biomedical Imaging
• Cardiovascular Research
• Nanotechnology in Medicine

Background:

• Atherosclerosis is a significant cause of cardiovascular disease, characterized by plaque inflammation.
• Accurate imaging of plaque inflammation is crucial for monitoring disease progression and treatment efficacy.
• Ferumoxtran-10, an iron oxide nanoparticle, shows potential as an MRI contrast agent for cellular imaging.

Purpose of the Study:

• To evaluate the efficacy of Ferumoxtran-10 for imaging plaque inflammation in a murine model of atherosclerosis using MRI.
• To determine the optimal dose and timing for Ferumoxtran-10 administration to detect iron uptake in atherosclerotic plaques.
• To correlate MRI findings with histological assessments of iron deposition in plaques.

Main Methods:

• Atherosclerosis was induced in apolipoprotein E-deficient (apoE-/-) mice.
• Mice received varying doses of Ferumoxtran-10 (500 or 1000 micromol Fe/kg) or saline control.
• Ex vivo and in vivo MRI scans were performed at different time points post-injection.
• T2* mapping was used to assess changes in signal properties.
• Histological analysis (Prussian blue staining) quantified iron-positive areas.

Main Results:

• Ferumoxtran-10 uptake in atherosclerotic plaques was observed 48 hours after a 1000 micromol Fe/kg dose, showing a 1.3-fold increase in iron content compared to controls.
• A significant decrease in normalized T2* values was noted with increasing Ferumoxtran-10 doses (p=0.038).
• In vivo MRI demonstrated a 122% increase in contrast-to-noise ratio (CNR), indicating enhanced plaque visualization.

Conclusions:

• Ferumoxtran-10 is successfully taken up by atherosclerotic plaques in apoE-/- mice.
• This uptake alters plaque signal characteristics, enabling detection and imaging via MRI.
• Ferumoxtran-10 holds promise as an effective contrast agent for non-invasive imaging of plaque inflammation in atherosclerosis.