Grant: Project Grant

Fibrosis, or tissue scarring, may be seen in all life-sustaining organs after injury. The injury can take the form of an ischemic attack (loss of blood flow to the heart or brain), uncontrolled hypertension (heavier load on the heart), viral infection (lung scarring), systemic inflammation (diabetes), or alcohol abuse (liver cirrhosis). What begins as a wound healing process goes awry and becomes abnormally prolonged, initiating the build-up of scar and eventually causing organ failure. Unfortunately, fibrosis cannot be detected with medical imaging until the late stages, a timepoint when no effective treatment, other than organ transplantation, exists. This limitation hinders not only early disease detection (when fibrosis may be halted or reversed) but also the testing of novel anti-fibrosis drugs. In this project, we introduce a game-changing targeted imaging agent to highlight fibrotic (scar) tissue in the heart, even at early stages of fibrosis. Unlike current "fibrosis imaging" methods, our agent can selectively bind to collagen - the predominant ingredient of scar - and accumulate at the diseased site to offer high signal contrast on non-ionizing magnetic resonance imaging (MRI). Furthermore, our fibrosis-targeted agent is a safe and non-irradiative compound that is naturally eliminated by the body. Our goal in this project is to demonstrate the ability of this agent to detect active, expanding fibrosis post-ischemic infarction and progressive, diffuse fibrosis in hypertension. We will also demonstrate the value of our new fibrosis agent for monitoring the efficacy of early anti-fibrosis treatment post-infarction and in hypertensive disease. The results of this project will lay the groundwork for broader application of our new fibrosis-targeting MRI agent in conditions afflicting other organs. More importantly, it will offer a hitherto inaccessible window on early and ongoing fibrosis, thus providing an opportunity to guide novel anti-fibrosis therapies.