The complementary roles of dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose PET/CT for imaging of carotid atherosclerosis

Abstract

Purpose: Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and (18)F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473).

Methods: The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and (18)F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and (18)F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model.

Results: We found a significant inverse relationship between several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or (18)F-FDG PET metrics.

Conclusion: In this study we observed a significant, weak inverse relationship between inflammation measured as (18)F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. (18)F-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events.

FIGURE 1

Schematic view of image analysis in common carotid arteries. Dashed lines represent acquired PET/CT and MRI axial slices. Data from all the slices was used for the whole vessel analyses. Red dashed line, DCE-MRI slice. Orange dashed lines, PET slices surrounding the slice matched with DCE-MRI, included in the analysis to take into account possible mis-registrations between the two techniques. PET/CT = positron emission tomography/computer tomography; MRI = magnetic resonance imaging; DCE = dynamic contrast enhanced MRI

FIGURE 2

Correlation between DCE-MRI and mean TBR by PET/CT, in the carotid arteries of subjects with CHD or CHD risk equivalent. (A) Correlation between K^trans by DCE-MRI and mean TBR by PET/CT. (B) Correlation between K_ep by DCE-MRI and mean TBR by PET/CT. x axis, mean TBR; y axis, DCE-MRI variables. Black dotted line, regression line. K^trans = wash-in constant from plasma to tissue constant; K_ep = wash-out constant from tissue to plasma; TBR = target-to-background ratio.

FIGURE 3

Sample patient DCE-MRI and ¹⁸F-FDG PET/CT images showing the relationship between Gd-DPTA uptake and ¹⁸F-FDG uptake. (A–C) representative case with low arterial FDG uptake by PET/CT, but high Gd-DTPA uptake by DCE-MRI. (D–F) representative case with high arterial FDG uptake by PET/CT, but low Gd-DTPA uptake by DCE-MRI. (A) and (D) FDG PET image overlaid on CT image.; blue circle, common carotid artery; red circle, jugular vein. (B) and (E) T1W post-contrast MRI image. (C) and (F) kinetic modeling of Gd-DTPA uptake by DCE-MRI. X-axis, time (min); y-axis, concentration (mmol/L); blue dots, experimental data; red line, model fit. FDG = fluorodeoxyglucose; Gd-DTPA = gadolinium-diethylene triamine pentaacetic acid; SM = skeletal muscle; L = vessel lumen.