MR imaging of iron phagocytosis in intraluminal thrombi of abdominal aortic aneurysms in humans

Radiology. 2010 Mar;254(3):973-81. doi: 10.1148/radiol.09090657.

Abstract

Purpose: To prospectively determine if superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging could help visualize leukocyte phagocytic activities in human abdominal aortic aneurysms (AAAs).

Materials and methods: This study was approved by the institutional ethics committee; all patients gave informed consent. Preoperative MR imaging data, including unenhanced and SPIO-enhanced T1-, T2*-, and T2-weighted transverse images of the entire AAA, obtained 1 hour after contrast enhancement from 15 patients (mean age, 72.7 years +/- 8.2; range, 60-83 years), 10 men (mean age, 73.5 years +/- 7.9; range, 60-83 years) and five women (mean age, 71.2 years +/- 9.4; range 60-82), were retrospectively evaluated. Morphologic appearance and semiquantitative and contrast-to-noise ratio (CNR) analyses of the thrombi were performed. Thrombi were analyzed semiquantitatively at microscopy after staining with hematoxylin-eosin, CD68, and CD66b. Levels of promatrix metalloproteinase (pro-MMP)-2 and pro-MMP-9, MMP-2 and MMP-9, and their mRNA located in the thrombus were assessed by using zymography and quantitative reverse transcriptase polymerase chain reaction analysis. Nonparametric statistics of the Spearman rank correlation were calculated to evaluate correlations between the aneurysm thrombus signal level decrease after SPIO and the levels of CD68(+), CD66b(+) cells, pro-MMP-2 and pro-MMP-9, MMP-2 and MMP-9, and MMP-9 mRNA.

Results: The pre-SPIO CNRs in the luminal sublayer of the thrombus and the deeper thrombus were -10.20 +/- 12.69 and -5.68 +/-10.38, respectively. After SPIO, the CNRs decreased to -21.34 +/-13.07 (P < .001) and -12.44 +/- 14.56, respectively (P < .012). There was a significant linear correlation between the thrombus signal level decrease and the levels of CD68(+) and CD66b(+) cells, pro-MMP-9, and MMP-9 mRNA (P < .05).

Conclusion: MR imaging allows in vivo demonstration of SPIO uptake at the luminal interface of the thrombus. This uptake is correlated to the abundance of leukocytes.

Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090657/-/DC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Aortic Aneurysm / metabolism*
  • Aortic Aneurysm / physiopathology
  • Contrast Media / pharmacokinetics
  • Dextrans
  • Enzyme Precursors / metabolism
  • Female
  • Ferrosoferric Oxide / pharmacokinetics
  • Gelatinases / metabolism
  • Humans
  • Image Enhancement / methods
  • Immunohistochemistry
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Phagocytosis / physiology*
  • Prospective Studies
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / metabolism
  • Statistics, Nonparametric
  • Thrombosis / metabolism*
  • Thrombosis / physiopathology

Substances

  • Contrast Media
  • Dextrans
  • Enzyme Precursors
  • Magnetite Nanoparticles
  • Serine Endopeptidases
  • pro-MMP-9 activator
  • Gelatinases
  • progelatinase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • ferumoxides
  • Ferrosoferric Oxide