Hyperpolarized Nuclear Singlet States

Nuclear Magnetic Resonance (NMR) is a technique which uses the fact that the nuclei of many atoms act as tiny
radiotransmitters, emitting radio signals at precisely-defined frequencies, which can be detected by a carefully-tuned detector. The frequencies and strengths of the signals depend on the magnetic field in which the sample is placed: the higher field, the higher the frequency, and the stronger the signals. In an NMR experiment, the nuclei are first magnetized by placing a sample in a strong magnetic field for some time. A sequence of radiofrequency pulses is then applied to the sample, which then emits radiowaves which can be detected in the radio receiver. The pattern of emitted waves depends on what the nuclei experienced during the pulse sequence.

One useful feature is that the nuclei can "remember" what happened to them some seconds before the radiosignals are emitted. This "memory" property allows one to track movements such as chemical reactions, the random displacement of molecules, and the flow of blood and other fluids by NMR. Until recently, the "memory time" of the atomic nuclei was thought to be a fixed property of the substance under study, which could not be changed significantly by the way one does the experiment. However, our group showed in 2004 that for some substances the memory time could be extended by a factor of 10 or more by using special quantum states which are non-magnetic, called singlet states.

At roughly the same time, a group of researchers in Sweden, including our project partner Jan-Henrik Ardenkjaer-Larsen, developed a revolutionary method for increasing the amplitude of NMR signals by a factor of ten thousand or even more. This method is called dissolution-DNP and an instrument to implement this is built and marketed by the British company Oxford Instruments. However a drawback of the technique is that the greatly enhanced polarization (called hyperpolarization) dies out quickly.

In this project we will combine these two developments by using dissolution-DNP to generate hyperpolarization and then convert the hyperpolarized substances into singlet states, which have a much longer lifetime.

We will synthesize molecules which have the right properties to sustain the long-lived singlet states and perform hyperpolarized NMR imaging experiments, mapping out slow processes such as diffusion and flow. We also expect to develop methods that allow one to construct a map of the oxygen content of fluids such as blood.

In this way we will develop and demonstrate a range of new magnetic resonance methods with a wide range of applications in medicine, chemical engineering and materials science.

1. Academic impact

1.1 New knowledge and scientific advancement.
The research in this proposal is basic in nature. How are long-lived nuclear singlet states constructed? How can molecules be synthesized that support such long-lived states? How can these states be exploited to generate new technologies capable of new types of imaging, or enhancements to existing imaging modalities? How can parameters such as oxygenation levels be encoded in an NMR image, independent of the signal strength?

In addition the proposal is highly interdisciplinary involving organic chemistry, quantum physics, image processing, and medical imaging.

1.2 Worldwide scientific advancement
The proposal is part of an ongoing global collaboration with project partners from Denmark and the USA.

1.3 Development of new methodologies, equipment, techniques, cross-disciplinary approaches.
The project fits perfectly into all of these categories. It uses new methodologies, equipment and techniques, in particular MRI and spin physics methodologies, and novel equipment such as HYPERSENSE as well as the customized equipment for sample shuttling and magnetization-to-singlet conversion. The project is highly cross-disciplinary, involving organic chemistry, quantum physics, and imaging.

1.4 Delivering and training researchers.
Three researchers will be directly involved in this project. One postdoctoral researcher will conduct organic syntheses but also be trained in advanced NMR and MRI techniques. The postdoctoral researcher in NMR will have expertise in NMR imaging and bring this expertise into the group, training the others.

2. Economic and Societal Impact
2.1 Cultural. Science is a cultural activity - especially basic science. Basic research of this nature is therefore culturally enriching.

2.2 Societal benefits. The research described here is directed towards the development of enhanced imaging modalities, of potentially great benefit to the diagnosis and treatment of a wide range of diseases. For example, enhanced imaging of flow would allow more precise diagnosis of coronary disease and other circulatory disorders. Imaging of oxygen levels would be invaluable for the assessment of cancer treatments, since a successful cancer treatment is associated with a rise in the local oxygenation, long before visible signs of cancer regression can be noted. These new modalities can therefore considerably increase the efficacy of treatments while reducing cost.

2.3 Economic benefits. Magnet technology is a strength of UK engineering so enhancements in NMR and MRI are of long-term economic benefit to the UK. In particular Oxford Instruments has invested heavily in HYPERSENSE technology so that advances in this technology are very important for that key company, which is a UK success story.

Improved efficiency in the treatment of diseases such as stroke and cancer due to the new ability to image oxygen levels will reduce the cost burden on health services.

The training of researchers in advanced NMR and MRI techniques and their associated theory will equip UK industry to compete better in these areas in the future, bringing further economic benefits.

2.4 National security and social welfare. Improvements to medical treatment improve social welfare. The pursuit of cross-continental scientific cooperation is beneficial for national security (as opposed to some other uses of government funds).