Long-lived Nuclear Hyperpolarization of Methyl Groups

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. In an NMR experiment, the nuclei are first magnetised by placing a sample in a strong magnetic field for some time. A sequence of radiofrequency pulses is then applied to the sample, which subsequently emits radiowaves which are detected in the radio receiver. The pattern of emitted waves provides information on the chemical composition and spatial distribution of the sample.

In ordinary circumstances, the NMR and MRI signals emitted by the nuclei are relatively weak, since the magnetic moments of the nuclei point in random directions. In 2003, a revolutionary method was developed for causing the nuclei to temporarily line up with each other, increasing the strength of NMR signals by a factor of ten thousand or even more. This method is called dissolution-DNP (where DNP stands for "dynamic nuclear polarization") 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.

Our group showed in 2004 that for some substances the decay time could be extended by a factor of 10 or more by using special quantum states which are non-magnetic, called long-lived states.

Last year evidence was presented that chemical groups called methyl groups (CH3) support long-lived states. These small symmetric groups are very common in chemistry and biology. A methyl group has the shape of a small propellor and usually rotates very rapidly with respect to the rest of the molecule. Our group showed that this propellor motion gives rise to a certain class of long-lived states. We used our theory to explain some prior results that had not been explained before, and performed a first series of experiments to validate the theory.

In this project we will combine these developments to generate methyl long-lived states that are strongly hyperpolarized and give rise to greatly enhanced NMR signals. We propose methods for validating and exploiting these states in molecules containing methyl groups, which are very common in natural substances. The project involves an interdisciplinary combination of quantum mechanics, engineering, experimental spectroscopy, and chemical synthesis, all of which are essential for the success of the project. 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 maintained in methyl groups, and how can those states be accessed? What are the best methods for polarizing such states? What are the best methods for converting the hyperpolarized methyl long-lived states into enhanced NMR signals? Can chemical reactions trigger the release of hyperpolarization from the methyl long-lived state?

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

1.2 Worldwide scientific advancement
The proposal is part of an ongoing collaboration with project partners from France.

1.3 Development of new methodologies, equipment, techniques, cross-disciplinary approaches.
The project uses new methodologies, equipment and techniques, in particular MRI and spin physics methodologies, and the development of novel hyperpolarization equipment and customised equipment/methodology for sample injection and magnetization-to-singlet conversion. The project is highly cross-disciplinary, involving organic chemistry, quantum physics, imaging, biochemistry, and reaches out into clinical medicine.

1.4 Delivering and training researchers.
Benno Meier (researcher CoI) will be given the opportunity to lead the project and to train as a research leader of the future. The careers of Giuseppe Pileio, Javier Alonso Valdesueiro and Lynda Brown will be furthered by their participation in this highly ambitious and multidisciplinary project. We will endeavour to recruit a graduate student to the project funded by other means, although this can no longer be assured due to the unwise EPSRC policy of not funding graduate students on research projects.

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, especially early detection of cancer and better characterisation of its response to treatment. 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. GE also has facilities located in the UK. The technologies developed in this project may underpin new startup companies.

Improved efficiency in the treatment of diseases such as stroke and cancer 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. Scientific and medical improvements improve social welfare and is beneficial for national security (unlike some other common uses of government funds).