This thesis contains 17 chapters about two major subjects. Part I focuses on the effects of chronic total occlusion percutaneous coronary intervention (CTO PCI) on myocardial ischemia reduction measured by [15O]H2O positron emission tomography (PET) perfusion imaging, on myocardial functional recovery measured by cardiac magnetic resonance imaging, on prognosis in terms of all-cause death and myocardial infarction, and on quality of life in terms of chest pain or dyspnea on exertion. Including two chapters describing in detail the diagnostic work-up as advised by the European and American guidelines and the current practice in patients with a CTO, this part of the thesis provides essential knowhow for judicious patient selection for CTO PCI. Part II investigates the feasibility and incremental value of several new (non-)invasive techniques to improve the diagnosis or treatment of coronary artery disease (CAD), including 1) an individualized segmentation model for quantitative PET perfusion imaging, 2) the coronary lumen volume to left ventricle mass ratio as measured by coronary computed tomography angiography (CCTA), 3) on-site CCTA through an augmented-reality glass during the PCI procedure to guide coronary stent implantation, 4) the use of a bioresorbable vascular scaffold in stable CAD, and 5) serial coronary artery calcium scoring to detect and predict myocardial ischemia.