HyperStore: Singlet states and supercritical fluids for storage and transport of hyperpolarised spin order

Nuclear magnetic resonance (NMR) is a versatile analytical tool with applications ranging from basic physics to medicine. In its imaging mode, MRI, it provides information on anatomy, metabolism and biological functions. However, NMR has low sensitivity, making many of its uses difficult and others impossible without some form of signal enhancement. For example, metabolic imaging of human cancer by MRI was only made possible by the recent introduction of nuclear spin hyperpolarisation methods. Among these methods, dissolution dynamic nuclear polarisation (dDNP - central to this proposal) prepare a very high degree of nuclear spin polarisation that can increase the signal-to-noise ratio up to 10,000 times. However, despite this enormous enhancement, in-vivo applications remain on the borderline of feasibility because of the relatively short lifetime of the enhanced polarisation. For example, the spatial resolution of hyperpolarised MRI images of cancer metabolism is compromised by the loss of signal during transport and purification of the hyperpolarised material. Improvements to post-hyperpolarisation protocols, allowing transport of hyperpolarised material, would therefore improve emerging techniques and open up new areas of research and applications.

The proposed research will address three interconnected main obstacles: the lack of purity of the hyperpolarised material (electron radicals are required by the hyperpolarisation technique); the limited lifetime of hyperpolarised magnetisation (the presence of radicals and many other intrinsic factors make nuclear spin polarisation to decay over time, a mechanism know as spin relaxation); the limited mobility of the polarising equipment (dissolution-DNP equipment is expensive and bulky and the limited lifetime of the hyperpolarised agents makes it impossible to transport the agent for significant distances. The point-of-use is therefore confined to the near vicinity of the point-of-production).

In order to overcome these obstacles we will use supercritical-CO2 chromatography to rapidly and efficiently purify the hyperpolarised material. Because spin polarisation storage times are roughly inversely proportional to viscosity, and because supercritical-CO2 has a viscosity 10-30 times lower than that of conventional solvents, we will also store the purified material under supercritical-CO2, potentially extending the length of storage time by 5-10 times. We will then explore extending storage time further by using long-lived states and by freezing the hyperpolarised solution under liquid nitrogen, freezing molecular motion and therefore minimising relaxation losses. We aim to extend storage of hyperpolarised material to over two hours, increasing distance between the point-of-production and the point-of-use. We also intend to build a convenient and portable transport device to enable transport of hyperpolarised material over long distances (as allowed by maximum lifetime achieved) with loss of no more than 50% of polarisation.

Societal Impact. The proposed research aims to extend the lifetime of hyperpolarised material, and improve methods for handling it. Hyperpolarised material generates substantially enhanced NMR/MRI signals (by over 10,000 times) and is important in a variety of areas such as materials science, catalysis and clinical medicine. Human clinical trials conducted in the USA showed that hyperpolarised NMR can be used to characterize cancer in a way that is inaccessible to other methods. Cheaper and more widespread use of such technology may lead to early detection of cancer and better characterisation of its response to treatment. Consequently, new modalities may increase treatment efficacy while reducing cost.
It is also important to have an informed society, and we will use the internet as a rapid, worldwide medium to maximise dissemination. In addition, the University scientific press will be used to communicate crucial developments to the non-expert public. Finally, we will disseminate our results using scientific video journals, a new format that is direct and user-friendly.

Economic Impact. There is a good chance that the engineering and methodological parts of this project will give rise to IP that may be the basis for a new start-up company; especially if hyperpolarised material lifetimes are long enough to allow the material to be generated at a central site (possibly a company) and transported to the point-of-use in the hyperpolarised state (similar to PET, which uses centralized "hot lab" production). We will work in coordination with the Research and Innovation Services (RIS) and the IP team at the University of Southampton to explore the possibility of patent filing, engage with industries and setup a start-up company.