Detection of the vulnerable atherosclerotic plaque is the “holy grail” in cardiovascular research. Early and accurate identification of rupture-prone plaques, holds the potential to prevent life-threatening thrombotic events and enable efficient, precise, plaque-specific treatment strategies. Towards addressing this challenge multi-modal molecular imaging techniques have been used, with hybrid PET-MRI imaging standing at the forefront of these efforts. Aim of the current proposal is to employ cutting-edge innovative simultaneous pre-clinical PET/MRI technology and assess its efficacy in identification of the vulnerable atherosclerotic plaque. The rupture-related molecular mechanism, which is investigated in the proposed project is the calcium deposition encountered in vulnerable plaques. For this purpose, we will employ 18FNaF, which is a PET-radiopharmaceutical holding the potential to selectively target and visualize early-stage micro-calcifications, which are associated with plaque instability. The project objectives will be tested in a recent innovative mouse model, the ApoE-/-Fbn1C1039G +/-, which is characterized by the development of rupture-prone plaques at specific time points. Furthermore, 18F-NaF findings will be validated with histological analyses, while associations with biochemical rupture-related markers will be explored. Finally, artificial intelligence-based models, incorporating imaging, biochemical, and histological data will be developed, aiming to improve risk stratification of coronary disease in the pre-clinical setting.
PRECISE-CAD aims to achieve the following objective: • Assessment of the efficacy of 18F-NaF PET/MRI studies to detect vulnerable atherosclerotic lesions and differentiate them from stable, low-risk for rupture plaques. • Quantification of early-stage micro-calcifications taking place in unstable plaques via quantification of 18F-NaF activity seen on PET and correlation with biochemical markers of inflammation and histopathological data. • Computational simulation of blood flow and rupture related mechanisms, via integration of functional data provided from PET with anatomic and functional information acquired from MRI. • Development of computational techniques for vascular wall movement correction caused by cardiac and respiratory function, allowing the detection of very small foci of uptake of the employed PET-radiopharmaceutical (18F-NaF) by the walls of the coronary arteries. • Integration of imaging markers obtained from PET/MRI studies with bio-engineering models incorporating imaging, biochemical, and histological data, aiming to improve risk stratification of coronary artery atherosclerotic plaques.
