Abstract
Introduction: Accurate non-invasive visualization and quantification of coronary atherosclerosis may greatly facilitate clinical research and practice, but the lack of suitable human-sized atherosclerosis models with progressive coronary lesions has hampered development and validation of reliable imaging techniques. Methods: D374Y-PCSK9 transgenic minipigs with (n=7) or without (n=8) hypertension, induced by suprarenal aortic banding, were placed on a cholesterol-rich diet for 16 months. Wildtype minipigs (n=4) on normal diet served as disease-free controls. A T1-weighted inversion recovery fast gradient echo magnetic resonance imaging (MRI) sequence was used to acquire 1x1x1mm images of the coronary arteries. MRI scans were conducted following injection of a gadolinium labeled elastin specific contrast agent (LMI1174). Pigs were subsequently euthanized and the coronary arteries were processed for pathological analysis. LMI1174 was provided by Lantheus Medical Imaging under a material transfer agreement Results: Hypertension significantly augmented coronary fibroatheromas by more than 5-fold compared to normotensive transgenic pigs. No signal enhancement was observed in lesion-free coronaries of wildtype pigs. In hypertensive pigs, there was a strong correlation between plaque area measured by MRI and plaque area measured postmortem r2=0.84, p=0.02 (Fig 1). Conclusions: Hypertensive transgenic minipigs with accelerated coronary atherosclerosis provide a useful model for coronary imaging. Using this model we were able to develop a high-resolution isotropic LMI1174-enhanced scanning technique that accurately depicts coronary atherosclerotic lesion size and distribution. Figure 1: A) Digitally unfolded and color coded MRI of the LAD (left) and corresponding sudan IV stained segment opened and viewed en face (right). B) Cross-sectional MRI of another LAD and corresponding histological sections showing fibroatheromas.
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