Long-lived Nuclear Hyperpolarization of Methyl Groups

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

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.

Planned Impact

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).

Publications

10 25 50
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Alonso-Valdesueiro J (2018) Testing signal enhancement mechanisms in the dissolution NMR of acetone. in Journal of magnetic resonance (San Diego, Calif. : 1997)

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Bengs C (2018) SpinDynamica: Symbolic and numerical magnetic resonance in a Mathematica environment. in Magnetic resonance in chemistry : MRC

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Dumez JN (2017) Dynamic Nuclear Polarization of Long-Lived Nuclear Spin States in Methyl Groups. in The journal of physical chemistry letters

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Eills J (2017) Singlet order conversion and parahydrogen-induced hyperpolarization of 13C nuclei in near-equivalent spin systems. in Journal of magnetic resonance (San Diego, Calif. : 1997)

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Elliott SJ (2018) Hyperpolarized long-lived nuclear spin states in monodeuterated methyl groups. in Physical chemistry chemical physics : PCCP

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Elliott SJ (2016) Long-lived nuclear spin states in monodeuterated methyl groups. in Physical chemistry chemical physics : PCCP

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Elliott SJ (2016) Long-lived nuclear spin states in rapidly rotating CH2D groups. in Journal of magnetic resonance (San Diego, Calif. : 1997)

 
Description Methyl groups support long-lived states.
Exploitation Route Enhanced NMR and MRI
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description EPSRC Platform Grant
Amount £1,784,689 (GBP)
Funding ID EP/P009980/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 02/2022
 
Description European Research Council Advanced Grant
Amount € 2,762,223 (EUR)
Funding ID 786707 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 09/2018 
End 09/2023
 
Description Underpinning Equipment
Amount £1,999,999 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2018
 
Title Bullet-DNP equipment 
Description Device and control system for rapid dissolution of a solid polarized by dynamic nuclear polarization 
Type Of Material Improvements to research infrastructure 
Year Produced 2019 
Provided To Others? Yes  
Impact Research insights and advances 
 
Title Cryogenic NMR probe 
Description Equipment for performing NMR at cryogenic temperatures 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? No  
Impact Advances in scientific understanding from measurement results 
 
Title SpinDynamica software 
Description SpinDynamica software is a Mathematica-based system for analyzing, understanding, and simulating nuclear spin dynamics, with applications to NMR and MRI. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact Widespread use in the NMR community 
URL http://www.spindynamica.soton.ac.uk/
 
Description CH2D collaboration 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Country France 
Sector Academic/University 
PI Contribution NMR theory, measurements and methodology
Collaborator Contribution NMR theory, measurements and methodology. Quantum chemistry collaborations.
Impact see grant entries.
Start Year 2016
 
Description CH2D collaboration 
Organisation Pomona College
Country United States 
Sector Academic/University 
PI Contribution NMR theory, measurements and methodology
Collaborator Contribution NMR theory, measurements and methodology. Quantum chemistry collaborations.
Impact see grant entries.
Start Year 2016
 
Description Hyperpolarization collaboration 
Organisation Cambridge Cancer Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description dDNP collaboration 
Organisation Technical University of Denmark
Country Denmark 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation École Normale Supérieure, Paris
Country France 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Description dDNP collaboration 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution NMR methodology, theory and experiments.
Collaborator Contribution NMR methodology, theory and experiments.
Impact see grant entries.
Start Year 2016
 
Title SpinDynamica 
Description Large set of Mathematica packages for analyzing, simulating, and understanding NMR experiments. 
Type Of Technology Software 
Year Produced 2017 
Impact widely used in NMR community 
URL http://www.spindynamica.soton.ac.uk