Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making

Coronary microvascular dysfunction (CMD) is a major mechanism of myocardial ischemia and adverse cardiovascular outcomes in patients with angina or dyspnea, both in the absence and in the presence of obstructive coronary artery disease. Because the coronary microcirculation cannot be visualized directly with routine angiography, diagnosis depends on physiological assessment. Non-invasive imaging has moved beyond relative perfusion analysis toward quantification of resting and hyperemic myocardial blood flow and flow reserve. Positron emission tomography (PET) remains the most extensively validated non-invasive method and provides robust absolute flow measurements with strong prognostic evidence. Quantitative stress cardiovascular magnetic resonance (CMR) is rapidly maturing, combining high-resolution perfusion mapping with ventricular and tissue characterization without ionizing radiation. Transthoracic Doppler echocardiography offers an accessible, radiation-free estimate of coronary flow velocity reserve, whereas myocardial contrast echocardiography can assess myocardial blood volume and replenishment kinetics. Dynamic cadmium-zinc-telluride single-photon emission computed tomography and stress computed tomography perfusion extend flow quantification to more widely available platforms, although standardization and outcome validation remain less developed. Across modalities, interpretation requires attention to the adequacy of vasodilator stress, resting hemodynamics, diffuse epicardial atherosclerosis, scar, and technical factors. A reduced flow reserve is not synonymous with isolated microvascular disease and cannot identify acetylcholine-provoked vasospasm. This review provides a clinically oriented framework for selecting, performing, interpreting, and reporting non-invasive CMD testing; examines the evidence, strengths, and limitations of each modality; and defines situations in which invasive coronary function testing remains necessary. Future progress will depend on cross-platform standardization, automated quality control, disease- and sex-specific reference ranges, and prospective trials linking imaging-defined endotypes to effective treatment strategies.