Using Magnetic Resonance to Detect and Analyse Nerve Agent Adducts

Organophosphorus nerve agents have been used in chemical warfare for more than 50 years. In the body, such agents bind to biological materials to form nerve agent adducts. The presence of these adducts can allow assessment of human exposure, due to their long-term persistence in the body. Recent developments in ultra-high performance liquid chromatography have demonstrated the identification of nerve agent adducts in blood, urine and hair. However, the significant work-up of samples required for this technique can be time consuming. Magnetic resonance imaging (MRI) contrast agents could offer a unique solution to this. Due to their strong (magnetically-driven) dipolar interactions with water, even minute changes in surrounding molecular hydrodynamics can result in dramatic changes in their magnetic (relaxation) behaviour. These properties have previously been used to understand the properties of medical contrast agents, and water interactions at surfaces. In this project, we aim to harness the power of this characterisation technique as a new approach to the diagnosis of the presence of nerve agent adducts in patient samples. MRI-active contrast agents will be prepared with varying structural characteristics, and will be evaluated in terms of their interaction with nerve agent adducts and their analogues. Changing MRI signal upon interaction with the nerve agent will provide clear and strong evidence for positive nerve agent detection. The development of magnetic resonance imaging (MRI) to identify the presence of such nerve agent adducts in patient samples could revolutionise their detection and avoid the need for significant sample processing.

Key objectives of the project:
To develop MRI-active agents capable of showing a clear change in the MRI signal upon interaction with a nerve agent species
Novel science of the project:
Developing MRI as a diagnostic technique for a novel approach to detect nerve agents after human exposure.