Intravascular optical coherence tomography (IV-OCT) is used to inform doctors about the shape and structure of hardened artery buildups, torn arteries, and blood clots in the heart. While the method is useful for anatomical imaging, researchers believe it can be pushed further to realize its potential to assist in earlier detection and risk assessment of heart conditions. A new contrast imaging agent, developed at the University of Ottawa and designed specifically for use with IV-OCT, could make it possible to use IV-OCT to identify the initial signs of heart disease and stratify patient risk. The new contrast agent, named AuSC@(13FS)2, is made of gold superclusters (AuSCs) that work with the IR light used in IV-OCT. The AuSCs maximize light scattering to improve the clarity of IV-OCT images. The superclusters, which are aqueously dispersible, facilitate plasmon hybridization to enhance light scattering at the IV-OCT laser line (approximately 1350 nm). In vivo IV-OCT molecular imaging of intravascular inflammation with AuSC@(13FS)2. Courtesy of Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01802-2. The researchers coated the AuSCs with a polymer to stabilize and allow targeting molecules to be attached to them. The polymer coating reinforces the uniformity of the AuSCs and provides a functional handle for targeting the new contrast agent. “We’ve found a simple and quick way to produce these gold superclusters,” professor Adam J. Shuhendler, who led the research, said. “We can also adjust them to make them perfect for improving IV-OCT imaging.” During the study, the research team targeted AuSC@(13FS)2 to intravascular P-selectin, an early vascular endothelial marker of inflammation. The contrast agent showed strong binding to P-selectin in laboratory testing. In a rat model of intravascular inflammation, where the strength of the signal correlated with the severity of vascular inflammation, the new contrast agent was shown to improve IV-OCT molecular imaging results. The researchers found that AuSC@(13FS)2 created distinct reflections in the IV-OCT images, similar to those seen with stents, when it bound to the inflamed blood vessels. They also observed a direct link between the amount of P-selectin and the number of reflections seen in the images, which suggests that the approach taken in the study could be used to measure the severity of inflammation. The AuSC-based contrast agent is tailored to clinical use and can be integrated into clinically relevant workflows. This will allow physicians and others to obtain detailed molecular information using AuSC@(13FS)2 without having to change the existing IV-OCT procedures used by their clinics. The researchers believe the new contrast agent will be a major advancement for the imaging and diagnosis of heart disease. By enabling detailed imaging with IV-OCT, AuSC@(13FS)2 could offer new opportunities for early detection and the development of treatments that are tailored to the individual. “Our new contrast agent could lead to more personalized heart disease treatments,” Shuhendler said. “This technology might help doctors detect heart diseases earlier and assess the risk more accurately by providing detailed information about the blood vessels.” The research was published in Nature Nanotechnology (www.doi.org/10.1038/s41565-024-01802-2).