Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET

Abstract

Objective: The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis.

Methods and results: Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis).

Conclusions: DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti-angiogenic therapies.

Fig 1

At week 2 after initiation of 0.3% high cholesterol diet, the animals receive the first balloon injury and the second one at week 6; at week 8 they are switched to 0.15% high cholesterol diet. Four months after diet initiation the animals undergo imaging and are then sacrificed.

Fig 2

Representative axial view of an atherosclerotic plaque before (a), 48 seconds (b), 192 seconds (c) and 12 minutes (d) after injection of contrast agent during DCE-MRI acquisition. The red arrows indicate the enhancing abdominal aorta (magnified view provided at the bottom right of each panel).

Fig 3

Signal intensity versus time curve representing the uptake of contrast agent in the plaque ROI following contrast agent injection for each rabbit; x axis: time (min); y axis: signal intensity (a.u.). Black arrow indicates contrast agent injection. Vertical dashed black bars indicate time points used for AUC evaluation.

Fig 4

a) Representative color coded AUC map by DCE-MRI b) representative histology slice showing CD31 neovessels staining. Magenta arrow indicates neovessel rich area c) representative FDG-PET image, showing 18F-FDG uptake along the whole abdominal aorta, with one focal spot of higher uptake(red markers, lower panel).

Fig 5

Correlation between AUC by DCE-MRI (2 min after contrast agent injection) and neovessels count in the intima (a) and total neovessels (plaque and adventitia, b). Blue circles: data points; black dashed line: regression line; dot-dashed red line: 95% confidence intervals.

Fig 6

Correlation between 18F-FDG SUV and neovessels count in the intima(a) and total neovessels (plaque and adventitia, b). Blue circles: data points; black dashed line: regression line; dot-dashed red line: 95% confidence intervals.