Project Summary Coronary bypass graft surgery (CABG) improves the lives of patients with coronary disease (CAD) as a group, but 20% of patients remain symptomatic one year after surgery. In clinical practice CABG decisions are largely driven by stenosis severity determined from invasive angiography despite the known relevance of functional CAD parameters. This practical impasse will continue to exist without clinically available, high-resolution, quantitative functional imaging, and a better understanding of the clinical outcomes in relation to anatomical (angiography) and functional (ischemia, scar tissue) factors. The long-term goal is to improve outcome of CABG through personalized imaging-guided care. The overall objective of this proposal is to identify determinants of myocardial flow restoration (ischemia reduction), and develop integrated imaging tools for individualized, lesion-specific CABG decision-making, and computational flow simulations based on the patient’s anatomy and function to predict the hemodynamic outcome. Supported by studies using invasive FFR-guided CABG, the rationale for the proposed research is that integration of anatomical (angiography) and functional information (ischemia, scar tissue) will identify individual coronary vessels that will benefit from revascularization, and individual optimization of surgical procedures by flow simulations will maximize clinical benefit of CABG for patients with CAD. Supported by promising preliminary data, three specific aims are proposed: 1) Prospectively identify angiographic, functional and clinical baseline determinants of outcome after CABG, defined as improvement of myocardial perfusion (ischemia reduction) and angina symptoms;; 2) Develop and validate a comprehensive imaging strategy and clinically applicable tool that integrate high- resolution angiographic and quantitative functional information (ischemia, viability) for per-vessel/lesion revascularization decisions;; 3) Develop and validate new multi-parametric computational flow simulations, with incorporation of functional imaging data, which allows for prediction of individual hemodynamic outcome and ultimately surgical optimization based on virtual hemodynamic results. This approach is innovative because new imaging techniques will advance the field’s understanding of CABG physiology, and new clinically applicable tools will be developed for comprehensive clinical decision-making and optimized surgical planning. The acquired knowledge and developed tools are applicable to other vascular contexts, and may also be instrumental for new therapeutic innovations. The proposed research is significant because identification of CABG outcome determinants, and new solutions for comprehensive decision-ma...