Abstract

Vulnerable or high-risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events when they rupture. In this study, polyethylene glycol (PEG)-micelles that incorporate a gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) amphiphile were used as an MR contrast agent. In an approach inspired by lipoproteins, the micelles were functionalized with tyrosine residues, an aromatic, lipophilic amino acid, to reach the lipid-rich areas of atherosclerotic plaque in a highly efficient manner. These micelles were applied to apolipoprotein E-/- (ApoE -/-) mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T1-weighted (T1W) high-resolution MRI at 9.4T before and up to 48 h after the administration of the micelles. PEG-micelles modified with 15% tyrosine residues yielded a significant enhancement of the abdominal aortic wall at 6 and 24 h postinjection (pi) as compared to unmodified micelles. Fluorescence microscopy on histological sections of the abdominal aorta showed a correlation between lipid-rich areas and the distribution of the functionalized contrast agent in plaque. Using a simple approach, we demonstrated that lipid-rich areas in atherosclerotic plaque of ApoE-/- mice can be detected by MRI using Gd-DTPA micelles.

Original languageEnglish
Pages (from-to)1195-1201
Number of pages7
JournalMagnetic Resonance in Medicine
Volume62
Issue number5
DOIs
StatePublished - Nov 2009

Keywords

  • Atherosclerosis
  • Contrast agent
  • Lipid core
  • MRI
  • Micelle

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