Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent

Circ Cardiovasc Imaging. 2013 Mar 1;6(2):285-94. doi: 10.1161/CIRCIMAGING.112.000119. Epub 2013 Jan 24.


Background: The accumulation of macrophages in inflamed atherosclerotic plaques has long been recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomal-iodine nanoparticle contrast agent for computed tomography imaging of macrophage-rich atherosclerotic plaques in a mouse model.

Methods and results: Liposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and computed tomography imaging in the RAW 264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy computed tomography imaging using this formulation in apolipoprotein E-deficient (ApoE(-/-)) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their colocalization with a small fraction (≈2%) of the macrophages in the plaque.

Conclusions: The results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomal-iodine nanoparticle contrast agent and dual-energy computed tomography.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta* / metabolism
  • Aorta* / pathology
  • Aortic Diseases / diagnostic imaging*
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortography / methods*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cell Line
  • Contrast Media* / administration & dosage
  • Contrast Media* / metabolism
  • Disease Models, Animal
  • Feasibility Studies
  • Flow Cytometry
  • Liposomes
  • Macrophages / diagnostic imaging
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Nanoparticles*
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Time Factors
  • Tomography, X-Ray Computed*
  • Triiodobenzoic Acids* / administration & dosage
  • Triiodobenzoic Acids* / metabolism


  • Apolipoproteins E
  • Contrast Media
  • Liposomes
  • Triiodobenzoic Acids
  • iodixanol