Dual-energy CT imaging of atherosclerotic plaque using novel ultrasmall superparamagnetic iron oxide in hyperlipidemic rabbits

Acta Radiol. 2023 Apr;64(4):1718-1724. doi: 10.1177/02841851221131904. Epub 2022 Oct 13.

Abstract

Background: A study using magnetic resonance imaging (MRI) revealed that ultra-small superparamagnetic iron oxide is phagocytosed by macrophages. However, MRI has limitations in obtaining clear images due to its poor spatial and temporal resolutions.

Purpose: To examine whether the use of dual-energy computed tomography (DECT) facilitated the visualization of carboxymethyl-diethylaminoethyl dextran magnetite ultra-small superparamagnetic iron oxide (CMEADM-U) accumulation in arteriosclerotic lesions using hyperlipidemic rabbits.

Material and methods: CMEADM-U at 0.5 mmol Fe/kg was administered to Watanabe hereditary atherosclerotic (WHHL) rabbits (n = 6, 24 sections) and New Zealand white (NZW) rabbits (n = 2, 6 sections). After 72 h, DECT was performed to prepare virtual monochromatic images (35 keV, 70 keV) and an iron-based map. Subsequently, the aorta was collected along with hematoxylin and eosin staining, Berlin blue (BB) staining, and RAM11 immunostaining.

Results: In the WHHL rabbits, CMEADM-U accumulation was not observed at 70 keV. However, CMEADM-U accumulation consistent with an arteriosclerotic lesion was observed at 35 keV and the iron-based map. On the other hand, in the NZW rabbits, there was no accumulation of CMEADM-U in any images. Further, there were significant differences in the iron-based map value at the site of accumulation among the grades of expression on BB staining and RAM11 immunostaining. In addition, there was a good correlation at 35 kev and iron-based map value (r = 0.42; P < 0.05).

Conclusion: DECT imaging for CMEADM-U facilitated the assessment of macrophage accumulation in atherosclerotic lesions in an in vivo study using a rabbit model of induced aortic atherosclerosis.

Keywords: Dual-energy computed tomography; atherosclerotic plaque imaging; iron-based map; macrophage; ultra-small superparamagnetic iron oxide.

MeSH terms

  • Animals
  • Atherosclerosis* / diagnostic imaging
  • Atherosclerosis* / pathology
  • Contrast Media
  • Dextrans
  • Ferrosoferric Oxide
  • Iron
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles*
  • Plaque, Atherosclerotic* / diagnostic imaging
  • Plaque, Atherosclerotic* / pathology
  • Rabbits
  • Tomography, X-Ray Computed

Substances

  • ferumoxtran-10
  • ferric oxide
  • Dextrans
  • Contrast Media
  • Magnetite Nanoparticles
  • Ferrosoferric Oxide
  • Iron