The recognition of the ubiquity of substantial but non-" ow limiting lesions that may be at high risk for subsequent plaque rupture and cannot be identi! ed by coronary angiography has resulted in a paradigm shift in thinking about the pathophysiology of coronary artery disease, with the focus no longer solely on the degree of arterial luminal narrowing. This growing need for more information about coronary atherosclerosis in order to identify patients and lesions at risk for complications during PCI and for future adverse cardiac events has been the primary impetus for the development of novel intra-coronary imaging methods, able to detect plaque composition. The introduction of intravascular ultrasound (IVUS) initially allowed a detailed evaluation of coronary atherosclerosis, but its limited resolution (axial 100-200 μm) precluded the visualization of certain microstructure and its capability to characterize coronary plaques, based on their greyscale-IVUS appearance, is limited. For these reasons, some other ultrasound and light based intra-coronary imaging techniques have been developed in order to provide tissue characterization of the coronary plaques.