The goal of this research project is to design and develop novel iodinated polysulfides as biodegradable macromolecular blood pool X-ray computed tomography (CT) contrast agents. There is an unmet clinical need for safe and effective blood pool contrast agents for clinical diagnostic imaging and image-guided interventions. Currently clinical agents have a transient blood half-life. High dose and multiple injections are often used to generate sufficient contrast enhancement in many clinical protocols. However, high dose may cause contrast-induced nephropathy. Although nanosized CT have agents have been reported, their clinical use is limited by the safety concerns associated their slow clearance from the body. In this exploratory research project, we propose to develop novel biodegradable macromolecular blood pool CT contrast agents to address the limitations of clinical CT agents and nanosized agents and the unmet clinical need. We will first design, synthesize and characterize iodinated polysulfides as biodegradable macromolecular blood pool CT contrast agents and determine their in vitro and in vivo degradability and clearance in an animal model in the specific aim 1, and then determine the effectiveness of the novel blood pool CT contrast agents for cardiovascular imaging, cancer imaging and quantitative perfusion imaging in an animal tumor model in the specific aim 2. Our long-term goal is to develop a safe and effective biodegradable macromolecular blood pool CT contrast agent for clinical cardiovascular imaging, cancer imaging, perfusion imaging and image- guided interventions.