Cardiovascular molecular imaging is a rapidly emerging area offering considerable promise for the evaluation of patients with heart and vascular disease. While proof of concept studies using novel imaging agents and micro PET have been conducted in mouse models of heart disease, their translation to humans and large animal models has been problematic since the human heart is 2000 times larger and dosimetry and tracer localization are considerably different. This proposal requests support to advance preclinical and clinical translational cardiovascular molecular imaging by acquiring a hybrid positron emission tomography (PET) and multidetector computed tomography (CT) scanner dedicated to research. It will support and enhance the ongoing investigational imaging programs of seven major users (supported by 9 RO1 awards and 2 K awards focused on cardiovascular imaging). The proposed GE Discovery VCT is a state of the art PET/CT scanner that will permit preclinical studies of vascular and myocardial structure coupled with molecular imaging using novel cyclotron generated radiopharmaceuticals developed at the adjacent UB Center for Positron Emission Tomography. The Center for Research in Cardiovascular Medicine and Toshiba Stroke Center at the University at Buffalo are interdisciplinary cardiovascular research centers that are recognized leaders in translational cardiovascular imaging. NIH supported studies routinely employ advanced cardiovascular imaging in porcine models of chronic ischemic heart disease and large animal models of stroke. Besides basic mechanistic research, active programs exist in therapeutics including vascular stents, in vivo gene transfer and cardiovascular repair with stem cells (mesenchymal stem cells and endothelial progenitor cells). There is also a large ongoing NIH supported clinical trial to determine if PET can predict the risk of sudden cardiac death in patients by quantifying the extent of hibernating myocardium and imaging inhomogeneity in sympathetic innervation using 11C-Hydroxyephedrine (Prediction of Arrhythmic Events with Positron Emission Tomography). The combined institutional expertise in large animal disease models including hibernating myocardium, coronary disease, cerebrovasular disease and ischemic cardiomyopathy along with patient oriented research in cardiac PET, quantitative image analysis and radiochemistry synthesis are unique strengths of this investigative team. The proposed instrument and synergy between these two teams will facilitate rapid advancements in the field of molecular imaging as applied to the cardiovascular system.
Heart disease continues to be one of the leading causes of death and disability. The proposed PET/CT system will advance bench to bedside research of potentially clinically relevant therapies by focusing on research at the preclinical to clinical translational interface. Such multilevel translational research ultimately has a high likelihood of directly impacting patient care and improving health outcomes. `