Polarizing agents for dynamic nuclear polarization
We describe polarizing agents for use in enhancing NMR and MRI signals via dynamic nuclear polarization (DNP). The polarizing agents include two or more paramagnetic centers, preferably two paramagnetic centers. In a preferred embodiment, the polarizing agent comprises two nitroxide radicals tethered by a polyethylene glycol chain of variable length. Signal enhancements of up to 175 have been achieved in comparison with factors of ˜45 at similar concentrations of monomeric radical such as TEMPO.
1. A method comprising steps of:
placing a sample that includes a polarizing agent within a magnetic field, wherein the polarizing agent is a ground state triplet molecule which comprises two or more unpaired electrons and at least two of the unpaired electrons have spin resonance frequencies that are separated by the spin resonance frequency of a selected nucleus within the sample; and
irradiating the sample with radiation that causes a mutual electron spin flip of the at least two unpaired electrons in combination with a nuclear spin flip of the selected nucleus so that the nuclear polarization of the selected nucleus is enhanced.
2. The method of claim 1 further comprising detecting the enhanced nuclear polarization by nuclear magnetic resonance.
3. The method of claim 1 further comprising introducing the sample into an organism and detecting the enhanced nuclear polarization by magnetic resonance imaging.
4. The method of claim 1 wherein the polarizing agent comprises two tethered radical molecules.
5. The method of claim 4 wherein the two tethered radical molecules are the same.
6. The method of claim 5 wherein the EPR linewidth of the polarizing agent is greater than the nuclear spin resonance frequency of the selected nucleus.
7. The method of claim 5 wherein the tethered radical molecules are nitroxides.
8. The method of claim 7 wherein the tethered radical molecules are TEMPO linked by polyethylene glycol.
9. The method of claim 4 wherein the two tethered radical molecules are different.
10. The method of claim 9 wherein maxima in spectral intensity of EPR spectra of the two tethered radical molecules are approximately separated by the nuclear spin resonance frequency of the selected nucleus.
11. The method of claim 9 wherein the tethered radical molecules are trityl and nitroxide radicals.
12. The method of claim 2 or 3 wherein the sample further includes an imaging agent and wherein the enhanced nuclear polarization is detected on a nucleus of the imaging agent after the enhanced nuclear polarization has been transferred from the selected nucleus to the nucleus on the imaging agent.
13. The method of claim 12 wherein the enhanced nuclear polarization is detected on a nucleus of the imaging agent with a longitudinal relaxation time constant that is greater than 10 seconds.
14. The method of claim 12 wherein the imaging agent is selected from the group consisting of sodium pyruvate-1- 13 C, acetate-1- 13 C, bicarbonate- 13 C, alanine-1- 13 C and 13 C-urea.
15. The method of claim 1 wherein in the step of irradiating, the sample is at a temperature of less than about 150 K.
16. The method of claim 15 wherein the sample further includes an imaging agent and wherein the enhanced nuclear polarization is detected on a nucleus of the imaging agent after enhanced nuclear polarization has been transferred from the selected nucleus to the nucleus on the imaging agent, the method further comprising melting or subliming the sample and then introducing the sample into an organism.
17. The method of claim 1 wherein the difference in spin resonance frequency of the at least two unpaired electrons results solely from g-anisotropy.
18. The method of claim 1 wherein the difference in spin resonance frequency of the at least two unpaired electrons results from a difference in isotropic g-value.
19. The method of claim 16 wherein the enhanced nuclear polarization is detected on the nucleus of the imaging agent by magnetic resonance imaging.
20. The method of claim 1 wherein the sample includes an amount of non-deuterated wate and the selected nucleus is a proton of the non-deuterated water.