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

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

A Millon  1 , S D Dickson, A Klink, D Izquierdo-Garcia, J Bini, E Lancelot, S Ballet, P Robert, J Mateo de Castro, C Corot, Z A Fayad
Affiliations

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

A Millon et al. Atherosclerosis. 2013 Jun.

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.

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Conflict of interest statement

Conflict of interest

E.L., S.B., P.R. and C.C. are employees of Guerbet; Z.A.F. received partial funding from Guerbet.

Figures

Fig. 1
Fig. 1
T2* weighted images pre and post USPIO injection for a “progression” rabbit at baseline (A) and at 6 months (B) and for a “regression” rabbit at baseline (C) and at 6 months (D). Graph and table comparing change in R2* show a non-significant decrease in the regression group.
Fig. 2
Fig. 2
Fused 18F-FDG PET/MR images at baseline and at 6 months showing a persistant strong FDG uptake in the abdominal aorta at 6 month in a “progression” rabbit (A,B) and a lesser uptake at 6 months in a “regression” rabbit (C,D). Graph and table comparing the mean SUV evolution in the 2 groups show a significant decrease of SUVmean in the regression group.
Fig. 3
Fig. 3
RAM 11 staining on histology slices showing a massive inflltration of macrophages in progression group (A, ×2 magnification) and a lower inflltration in regression group (B, ×2 magnification). Graph comparing the percentage of wall area occupied by RAM 11 staining show a significant difference in the two groups.
Fig. 4
Fig. 4
T2* weighted images pre (A) and post USPIO injection (B) show a loss of signal in the arterial wall in a rabbit from the progression group. Co-localization between Perls iron staining (C) and Ram 11 staining (D) (×4 magnification).
Fig. 5
Fig. 5
Graph showing correlation between SUVmean and Ram 11 staining and between change in R2* values and Ram 11 staining.
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