Matrix metalloproteinase-9 expression in carotid atherosclerotic plaque and contrast-enhanced MRI in a swine model.

BACKGROUND

A swine model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the preclinical evaluation of endovascular intervention. In this study we assess the association of matrix metalloproteinase (MMP)-9 expression and neovascularity in carotid atherosclerotic plaques with MRI patterns in a swine model.

METHODS

Carotid atherosclerosis models were created in miniswine using a combination of partial ligation and a high cholesterol diet. The animals were imaged in a 1.5 T MR scanner at 3 months and carotid arteries were obtained for histopathological and immunohistochemical examination. Contrast-enhanced T1-weighted imaging (T1WI) was used to match the histology findings. The contrast-to-noise ratio (CNR) of the plaques on T1WI and contrast-enhanced T1WI were measured and the association of MMP-9 expression and neovascularity in the carotid plaque with CNR on MRI was analyzed.

RESULT

Forty carotid artery segments were matched between MRI and histology. All segments were advanced carotid atherosclerotic plaques. The matched contrast-enhanced T1WI and histology slices showed good correlation for ratio of plaque size to lumen diameter (r=0.94, p<0.001). Plaque CNR on contrast-enhanced T1WI was higher in plaques with strong MMP-9 expression than in those with weak MMP-9 expression (p=0.05). Plaque CNR on contrast-enhanced T1WI was also higher in plaques with marked neovascularization than in those without (p=0.02).

CONCLUSIONS

Increased plaque CNR on contrast-enhanced T1WI is associated with MMP-9 expression and neovascularization in carotid atherosclerotic plaques and may be used to identify vulnerable plaques.