Researchers from the Institute of Biomedical Engineering at the University of Toronto have developed a novel MRI contrast agent that may enhance the early detection of inflammatory diseases by targeting nitric oxide (NO), a key molecule involved in the body’s immune response. The new agent activates in the presence of NO and provides a bright contrast in T1-weighted MRI scans, potentially allowing clinicians to monitor inflammation more effectively. This approach could eventually help in diagnosing conditions like heart disease, neurodegeneration, and cancer at earlier stages, potentially improving treatment outcomes.
This research was recently published in the journal ACS Sensors.
Nitric oxide plays a critical role in signaling within the body, but it also appears early in many chronic diseases, making it a valuable target for early disease detection. Current imaging techniques struggle to capture NO dynamics in deep tissues, limiting their clinical application. Optical methods like fluorescence and mass spectrometry cannot penetrate deep tissues, while other MRI-based approaches do not offer the sensitivity required to monitor the low levels of NO present in the body. This research addresses that gap by offering a more sensitive and specific imaging method using a NO-activatable MRI contrast agent.
“Our work aims to address a fundamental challenge in medical imaging—how to visualize key molecular changes in real-time, deep within the body, molecular changes that precede functional and structural alterations,” said Professor Hai-Ling Margaret Cheng, the corresponding author. “Nitric oxide is involved in many disease processes, so being able to track its presence and activity could open up new possibilities for diagnosing and treating inflammatory conditions.”
To develop this agent, the team designed a contrast agent based on manganese porphyrin. The agent is activated in the presence of NO, binds to tissue proteins, and accumulates in areas where NO is produced, producing a bright signal in MRI scans. The researchers tested the agent in vitro, confirming its specificity for NO and its lack of reactivity to other similar molecules. In a mouse model of acute myocardial inflammation, the agent increased T1 contrast by over 2.2 times in inflamed heart tissue compared to healthy tissue, demonstrating its ability to detect and track NO in living organisms.
“Our findings suggest that this NO-activated contrast agent can significantly improve the detection of inflammatory activity,” said lead author and PhD student Anlan Hong. “The enhanced sensitivity of this agent could lead to earlier diagnoses of diseases that involve nitric oxide, offering better prognosis and treatment options.”
Looking ahead, the team plans to investigate the value of early detection of inflammation in chronic conditions such as hypertension and heart failure. “The next step is to validate this approach in larger animal models and eventually clinical trials,” said Professor Cheng. “We’re hopeful that this new imaging tool will not only lead to very early and specific detection of inflammatory conditions but also guide the development of new targeted therapeutics.”