ProjectSummary Coronarybypassgraftsurgery(CABG)improvesthelivesofpatientswithcoronarydisease(CAD)asagroup, but20%ofpatientsremainsymptomaticoneyearaftersurgery.InclinicalpracticeCABGdecisionsarelargely drivenbystenosisseveritydeterminedfrominvasiveangiographydespitetheknownrelevanceoffunctional CAD parameters. This practical impasse will continue to exist without clinically available, high-resolution, quantitativefunctionalimaging,andabetterunderstandingoftheclinicaloutcomesinrelationtoanatomical (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) andfunctionalinformation(ischemia,scartissue)willidentifyindividualcoronaryvesselsthatwillbenefitfrom revascularization,andindividualoptimizationofsurgicalproceduresbyflowsimulationswillmaximizeclinical 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 afterCABG,definedasimprovementofmyocardialperfusion(ischemiareduction)andanginasymptoms;?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, withincorporationoffunctionalimagingdata,whichallowsforpredictionofindividualhemodynamicoutcome 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 clinicallyapplicabletoolswillbedevelopedforcomprehensiveclinicaldecision-makingandoptimizedsurgical planning.Theacquiredknowledgeanddevelopedtoolsareapplicabletoothervascularcontexts,andmay also be instrumental for new therapeutic innovations. The proposed research is significant because identification of CABG outcome determinants, and new solutions for comprehensive decision-making and procedural guidance, have the potential to improve the effectiveness (by complete functional revascularization) and efficiency of CABG (by avoiding futile grafts). For a large group of patients, these innovations willimprove thepatient-valued benefit of CABG(complications,symptoms), andalsodecrease costbyimprovedefficiencyofcare.