Atherosclerosis can cause serious cardiovascular diseases. The rupture of atherosclerotic plaque can lead to embolisms downstream and the occurrence of acute coronary syndromes such as myocardial infarction and stroke, which cause irreversible damage to patients or even lead to their deaths. Therefore, early detection of plaque lesions is very important to prevent lethal consequences of atherosclerosis. Diagnosis of the latent vulnerability of a plaque lesion relies on both structural and tissue chemical compositions. Structurally, the thickness of the fibrous cap is a reliable indicator of plaque vulnerability. Chemically, the intralesion lipid density is a parameter that correlates with the vulnerability of the lesion.1 Intravascular ultrasound (IVUS) and optical coherence tomography (OCT), currently the two most commonly used modalities in clinics for diagnosing cardiovascular diseases, allow direct tomographic visualization of cross-sectional images from inside the vessel lumen.2 IVUS has been used clinically to diagnose atherosclerosis for more than 20 years. However, IVUS has limited resolution of 50 to 200 µm, which is not enough to resolve the thin fiber cap of the high-risk vulnerable plaque with typical thicknesses of 50 to 60 µm. On the other hand, OCT can provide cross-sectional images of tissue microstructure with a spatial resolution on the order of 5 to 10 µm.3 Therefore, intravascular OCT can be used to accurately assess thickness of fibrous caps and other microstructure information of vulnerable plaques.4,5 Although OCT has been used for vulnerable plaque evaluation with its high resolution, it lacks molecular specificity for identification of tissue composition in plaques. Intravascular fluorescence molecular imaging endoscopy provides biomolecular information of atherosclerosis inside the blood vessel.6 Therefore, an integrated OCT/fluorescence imaging system7,8 combining high spatial resolution of OCT with molecular sensitivity of fluorescence imaging is capable of resolving both microstructure and biomolecular information at the same time.