Intravascular contrast agents in diagnostic applications: Use of red blood cells to improve the lifespan and efficacy of blood pool contrast agents

In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents (CAs) available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells (RBCs) as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.