Contents
grad

SABRE

Signal Amplification By Reversible Exchange

Parahydrogen provides magnetic resonance signal enhancement via reversible interactions.





Introduction to SABRE

We have used parahydrogen to study inorganic reaction mechanisms for many years. Others have used it to polarise organic materials which have recently found use in MRI studies. However, both these approaches require the addition of parahydrogen to the molecule that is to be observed. Consequently, they involve the chemical functionalisation of materials and require the accessibility of a suitable unsaturated precursor. This marks a substantial limitation of the parahydrogen approach.

Our new technique, Signal Amplification By Reversible Exchange (SABRE), achieves a similar result without any chemical change being necessary. The SABRE method delivers a proven 1000-fold increase in sensitivity. This 1000-fold signal gain means that NMR measurements which would have previously taken months can now be completed in seconds.

We are grateful to Professor Gary Green and colleagues of the York Neuroimaging Center (YNIC) for their assistance in this work.



Concept: Transfer of polarisation from parahydrogen to substrate

The images and videos shown below illustrate the concept behind this new method.


The SABRE method
Fig 1: Schematic representation of the SABRE method. The polarisation (represented by the orange colouring) is transferred from parahydrogen to a substrate which can then be seen by NMR and MRI.

Examples of spectra and images generated by the SABRE method

The following spectra and images were generated by Andreas Steingoetter, Ralph Adams and Michael Cowley.

Nicotinamide enhancement. MRI of pyrazine.
Fig 2: 13C spectrum of nicotinamide. This data was collected in a matter of seconds using SABRE. With conventional methods, this would have taken approximately three months.
Fig 3: MRI image of a SABRE-enhanced sample. Single average RAREst 1H image on a pyrazine sample on Bruker BioSpin 70/30 employing a 1350-fold signal gain. The data collected in 3 seconds that would otherwise take 42 days.


Pyridine enhancement.
Fig 4: Single average 1H True-FISP MRI image of polarised pyridine within a 0.5 mm slice at 9.4 T on a Bruker DRX system.




Video


There are five video sequences to download that demonstrate the method in operation.

Sample Preparation


Setting up a SABRE experiment; the iridium based catalyst and substrate are dissolved in deuterated methanol. Once transferred to an NMR tube, the system is ready to accept parahydrogen.




Polarisation


Hydrogen is flushed through the rig several times to remove any air before parahydrogen is introduced over the sample. Shaking increases the surface area of the solvent to increase the amount of H2 that dissolves.




NMR 400 Spectroscopy


A non-polarised sample is scanned on the 400 MHz spectrometer. By refreshing the parahydrogen and shaking, polarisation occurs and the signal appears enhanced.




NMR 600 Imaging


The same hyperpolarisation technique can be applied to an imaging experiment (MRI). This is an important step in the development of the technique for medical applications.




3T MRI Imaging


Using an MRI scanner produces the same results. Shaking the tube to induce hyperpolarisation before introducing the sample into the instrument.

If you would like further information about this research, the underlying technology or possibilities for collaboration, please email Helen Fagan on hf510@york.ac.uk.

Acknowledgements

This work was supported by the University of York, the White-Rose Health Innovation Partnership, the Engineering and Physical Sciences Research Council, the Medical Research Council, Biotechnology and Biological Sciences Research Council, the Spanish Ministry of Education and Science [Project Consolider ORFEO (CSD 2007-00006)], and Bruker Bio-Spin.

We are grateful to further funding from the EPSRC and Bruker Bio-Spin for further support to continue to develop the chemical basis of this work.

We also thank, R. Perutz, P. Walton, M. Hymers, S. Johnson, M. Mortimer, and K. Armour for advice and helpful discussions. We have filed a patent application, P115707GB, based on this work.

References