Abstract
This review highlights the evolving role of positron emission tomography (PET) in quantifying myocardial blood flow (MBF) and myocardial flow reserve (MFR) and its expanding clinical impact. The relative nature of perfusion assessment with single photon emission computed tomography often underestimates disease in patients with multivessel or microvascular involvement. Positron emission tomography (PET) enables absolute quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which provides deeper insights into coronary physiology. PET-derived MBF and MFR have shown clear diagnostic and prognostic value across a broad spectrum of conditions, including obstructive coronary artery disease, ischemia and angina without obstructive coronary artery disease, post-heart transplant cardiac allograft vasculopathy surveillance, diabetes, hypertension, and systemic inflammatory diseases. Impaired flow reserve consistently predicts adverse outcomes, even in the absence of visible perfusion defects. Newer tracers such as (18)F-flurpiridaz, with their favorable kinetics and logistical advantages, are poised to expand clinical accessibility. At the same time, innovations such as artificial intelligence-driven analysis and total-body PET promise greater reproducibility and efficiency, further integrating flow assessment into everyday practice. Professional society guidelines now recommend routine incorporation of flow quantification into stress PET imaging, yet barriers remain, including limited access, heterogeneity in protocols, and a need for outcome-driven trials. As technology and evidence evolve, PET-based flow quantification is positioned to become an essential tool in precision cardiovascular care, bridging the gap between physiology and clinical decision-making.