Mri Assessment of Endothelial Damage and Angiogenesis in Porcine Coronary Arteries Using Gadofosveset

S. Fjord Pedersen, W. P. Paaske, T. Thiem, S. Ringgaard, S. A Thrysøe, and W. Yong Kim Aarhus University Hospital, Aarhus, Denmark, 1Dept. of Cardiothoracic and Vascular Surgery T, Aarhus University Hospital, Skejby, Denmark, Dept. of Cardiology, Aarhus University Hospital, Skejby, Denmark, MR-center, Aarhus University Hospital, Skejby, Denmark, Dept. of Cardiology, and MR-center, Aarhus University Hospital, Skejby, Denmark Introduction: Endothelial damage and angiogenesis are essential in atherosclerotic plaque development and destabilization (1). Macromolecules in the blood may extravasate into the vessel wall through leaky neovessels or damaged endothelium. Gadofosveset is an MRI contrast agent that binds reversibly to albumin and may enter damaged tissue such as the atherosclerotic vessel wall together with albumin (2,3). We sought to examine whether contrast enhanced MRI using gadofosveset would enable the detection of endothelial damage and neovessels in balloon injured porcine coronary arteries. Methods: Ten pigs underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. After balloon injury, in-vivo and ex-vivo T1-weighted coronary MRI was performed after intravenous injection of gadofosveset. The ex-vivo MR images were matched with corresponding histological sections and correlated to endothelial damage and angiogenesis. Results: Ex-vivo coronary vessel wall MRI contrast enhancement was in agreement with extravasated Evans blue as a marker of endothelial damage with a kappa value of 0.64 (p<0.001) (Figure 1)). Sixty minutes post contrast, MRI showed contrast enhancement of the injured LAD as compared to the non-injured circumflex artery that served as control with a significant increase in the diameter of the artery (30±19 % versus 4±8%; P=0.01) (Figure 2)). There was a linear correlation between coronary MRI contrast-enhancement and microvessel density (r=0.78, p<0.001) (Figure 3). Conclusion: Contrast enhanced coronary MRI using gadofosveset is a promising approach for the non-invasive detection of endothelial damage and angiogenesis in the coronary artery wall