Monitoring plaque inflammation in atherosclerotic rabbits with an iron oxide (P904) and (18)F-FDG using a combined PET/MR scanner

Atherosclerosis. 2013 Jun;228(2):339-45. doi: 10.1016/j.atherosclerosis.2013.03.019. Epub 2013 Mar 26.

Abstract

Purpose: The aim of this study was to compare the ability of (18)F-FDG PET and iron contrast-enhanced MRI with a novel USPIO (P904) to assess change in plaque inflammation induced by atorvastatin and dietary change in a rabbit model of atherosclerosis using a combined PET/MR scanner.

Materials and methods: Atherosclerotic rabbits underwent USPIO-enhanced MRI and (18)F-FDG PET in PET/MR hybrid system at baseline and were then randomly divided into a progression group (high cholesterol diet) and a regression group (chow diet and atorvastatin). Each group was scanned again 6 months after baseline imaging. R2* (i.e. 1/T2*) values were calculated pre/post P904 injection. (18)F-FDG PET data were analyzed by averaging the mean Standard Uptake Value (SUVmean) over the abdominal aorta. The in vivo imaging was then correlated with matched histological sections stained for macrophages.

Results: (18)F-FDG PET showed strong FDG uptake in the abdominal aorta and P904 injection revealed an increase in R2* values in the aortic wall at baseline. At 6 months, SUVmean values measured in the regression group showed a significant decrease from baseline (p = 0.015). In comparison, progression group values remained constant (p = 0.681). R2* values showed a similar decreasing trend in the regression group suggesting less USPIO uptake in the aortic wall. Correlations between SUVmean or Change in R2* value and macrophages density (RAM-11 staining) were good (R(2) = 0.778 and 0.707 respectively).

Conclusion: This experimental study confirms the possibility to combine two functional imaging modalities to assess changes in the inflammation of atherosclerotic plaques. (18)F-FDG-PET seems to be more sensitive than USPIO P904 to detect early changes in plaque inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Abdominal* / diagnostic imaging
  • Aorta, Abdominal* / drug effects
  • Aorta, Abdominal* / pathology
  • Aortic Diseases / diagnosis*
  • Aortic Diseases / diagnostic imaging
  • Aortic Diseases / drug therapy
  • Aortic Diseases / pathology
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / drug therapy
  • Atherosclerosis / pathology
  • Atorvastatin
  • Contrast Media*
  • Dextrans*
  • Disease Models, Animal
  • Disease Progression
  • Fluorodeoxyglucose F18*
  • Heptanoic Acids / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Inflammation / diagnosis*
  • Inflammation / diagnostic imaging
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles*
  • Plaque, Atherosclerotic*
  • Positron-Emission Tomography*
  • Predictive Value of Tests
  • Pyrroles / pharmacology
  • Rabbits
  • Radiography
  • Radiopharmaceuticals*
  • Time Factors

Substances

  • Contrast Media
  • Dextrans
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Magnetite Nanoparticles
  • Pyrroles
  • Radiopharmaceuticals
  • ferumoxtran-10
  • Fluorodeoxyglucose F18
  • Atorvastatin