Cardiovascular disease is the world’s number one killer, taking the lives of an estimated 17.9 million people globally each year. The disease took more than 800,000 lives in the U.S. in 2020, according to the American Heart Association. Heart disease costs the U.S. over $400 billion each year. A better way is needed to address cardiovascular disease, and optical technologies are helping to discover it. Cardiovascular disease clinically manifests as the luminal narrowing of coronary arteries due to plaque buildup in the walls of the arteries or as occlusive thrombosis triggered by the abrupt rupture of a vulnerable plaque, causing obstruction of blood flow to the heart. Intravascular image-guided catheterization procedures have shown the potential to reduce the risk of cardiovascular death and adverse cardiovascular events. The use of intravascular imaging during treatment with stents, however, remains limited. Intravascular ultrasound (IVUS), the most commonly used intravascular imaging modality, can reliably quantify the lumen and plaque dimensions but cannot accurately assess plaque composition. Optical coherence tomography (OCT) can visualize microscopic features of a plaque. Combined IVUS-OCT imaging appears to enable evaluation of the arterial wall and plaque morphology and microstructure, though it cannot assess the vessel wall’s biochemical and functional properties. Hybrid intravascular imaging systems are urgently needed to enable a personalized therapy of high-risk individuals. More recently, various types of imaging — such as near-infrared spectroscopy and near-infrared fluorescence molecular, intravascular photoacoustic, and fluorescence lifetime imaging — have been adapted to intraluminal applications. These emerging techniques offer new ways to assess plaque pathobiology and functional properties in humans. The techniques aid in the detailed study of stent deployment and they detect features that have been associated with stent failure, such as the presence of lipid tissue and increased plaque burden at the edge of the stent, vascular inflammation, stent underexpansion or malapposition, and thrombus protrusion within the stent. But they are still far from being broadly used in catheterization procedures. Current intravascular standalone imaging techniques are limited in their ability to predict plaque progression and sudden changes in plaque structure (such as rupture or erosion) conducive to acute coronary syndromes. Hybrid intravascular imaging systems are urgently needed to enable a personalized therapy of high-risk individuals with established coronary artery disease. Access to the narrow and tortuous coronary arteries, however, requires optical catheter systems capable of not only efficiently delivering and collecting light from tissue via small-diameter fibers and generating high-quality images of the lumen and vessel wall with no imaging artifacts but also imaging the luminal surface quickly during pullback in pulsatile blood flow. In contrast to applications of optical imaging technology in oncology, in which the cancerous tissue is removed and then histopathologically analyzed, coronary vessels or plaques are not removed from patients. Thus no direct correlation between optical signatures measured in vivo and pathology can be achieved. Most of the studies validating emerging intravascular imaging modalities therefore use histology data from cadaveric hearts as a reference standard. This data, however, is not available at scale and cannot represent clinical practice where intravascular imaging is performed in a beating heart. Despite these limitations, there is consensus that multimodality imaging catheters outperform standalone intravascular imaging techniques in guiding stent implantation and detecting high-risk plaques. The broad adaptation of these technologies in clinical practice requires the familiarization of the clinicians with the data produced by the catheters. Industry and academia must work together to develop image processing methods to expedite image analysis and user-friendly systems for visualization of vessel pathology. Training the interventional community on these systems and conducting large outcome studies will provide needed evidence regarding the superiority of emerging light-based imaging modalities in guiding interventional therapy. Meet the authors Laura Marcu, Ph.D., is a professor of biomedical engineering and neurological surgery at the University of California, Davis. She received her doctorate in biomedical engineering in 1998 from the University of Southern California. Marcu’s research interest is in the area of biomedical optics, with a particular focus on research for the development of optical techniques for tissue diagnostics, including applications in oncology, interventional cardiology, and tissue engineering. She serves as director for the National Center for Interventional Biophotonic Technologies; email: lmarcu@ucdavis.edu. Christos Bourantas, M.D., Ph.D., is a consultant cardiologist at Barts Health Centre and honorary senior lecturer at University College London and Queen Mary University of London. He graduated from medical school at the University of Ioannina and received his doctorate there in 2005. Bourantas completed his cardiology training in 2011 in the U.K. then a postdoc research fellowship in Erasmus Medical Center’s Thoraxcentre and a CCT fellowship in interventional cardiology at Barts Health; email: cbourantas@gmail.com. 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