Grant: Project Grant

Heart disease remains a leading cause of illness and death, and many forms of heart damage are driven by early molecular changes that cannot currently be seen with medical imaging. One key molecule involved is nitric oxide (NO), a small signaling molecule that helps regulate blood flow, inflammation, energy use in heart muscle, and tissue repair. While NO can protect the heart, it can also contribute to long-term damage when its signaling becomes abnormal. Because of this dual role, NO has been a major target for drug development for over 30 years. However, many NO-targeted treatments have failed in clinical trials, largely because we do not understand when, where, and how NO acts in the living heart. The main challenge is that existing tools cannot directly measure NO activity inside the heart in real time. Current imaging methods only show the end results of disease, such as scarring or loss of function, long after NO-driven processes have already occurred. Without the ability to visualize NO itself, it is impossible to determine whether treatments fail because they target the wrong patients, the wrong stage of disease, or the wrong biological processes. To address this gap, our team has developed a new MRI contrast agent that safely and selectively responds to nitric oxide. Unlike conventional MRI agents, this probe is designed to highlight regions of active NO signaling, allowing us to create detailed maps of NO activity inside the living heart. Using this technology, we aim to understand how NO signaling patterns differ between types of heart disease, how they change over time, and how they influence treatment response. By directly imaging NO activity, this research will provide critical insight into why NO-targeted therapies succeed in some cases but fail in others. Ultimately, this work will support the development of more precise, mechanism-based treatments and improve outcomes for patients with heart disease.