Development of Hyperpolarised MRI Diagnostics for Nitric Oxide Tracing in Cardiovascular Pathologies

Supervisors: Prof Matteo Zanda, Prof Michael Frenneaux and Prof David Lurie

Nitric oxide (NO) plays a central patho-physiological role in several tissues including heart and vessels. NO is generated by one of three nitric oxide synthase enzymes (NOS) from the oxidation of the amino acid L-arginine with the generation of L-citrulline and NO. The ability to localise and quantify NOS enzyme activity using Magnetic Resonance (MR) imaging and spectroscopy would have considerable potential applications for the diagnosis and treatment of cardiovascular pathologies. Unfortunately traditional MR is affected by relatively low sensitivity and can be hardly used for imaging physiological processes in vivo. Hyperpolarised MR Imaging is an emerging technology with the potential to revolutionise MRI and provide the potential for assessment of biochemical pathways in-vivo with unprecedented specificity and spatial localisation. Here we will expand groundwork undertaken by our collaborators Professors S B Duckett and colleagues (University or York), for further developing hydrogenative and reversible-exchange hyperpolarisation (PHIP and SABRE technologies) for MRI. We have previously undertaken pilot work to demonstrate that a series of molecules designed in Aberdeen are hyperpolarisable ex-vivo and act as substrates for NO synthases. In this project the student will further develop these analogues and evaluate their use for ex-vivo and in-vivo assessment of NOS activity by hyperpolarised MRI.