Method for hyperpolarization transfer in the liquid state

Patent metadata

Field	Value
Publication number	US-9329246-B2
Application number	US-201213633899-A
Country	US
Kind code	B2
Filing date	Oct 3, 2012
Priority date	Oct 3, 2012
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

A method for producing a hyperpolarized sample for use in a magnetic resonance investigation has the following steps: a) providing a solid sample ( 50 ), containing long T 1 nuclei and short T 1 nuclei in the same molecules ( 51 ); b) hyperpolarizing the short T 1 nuclei in the solid sample ( 50 ); c) transforming the solid sample ( 50 ) into a liquid sample ( 52 ); and d) transferring the polarization of the short T 1 nuclei to the long T 1 nuclei within the molecules in the liquid sample ( 52 ) by Cross Polarization. The method can provide samples with hyperpolarized long T 1 nuclei, in particular 13 C or 15 N, in a simple and efficient way.

First claim

We claim:

1. A method for producing a hyperpolarized sample for use in a magnetic resonance investigation, the method comprising the steps of:
a) providing a solid sample containing long Tl nuclei and short T 1 nuclei in same molecules;
b) hyperpolarizing the short T 1 nuclei in the solid sample;
c) transforming the solid sample into a liquid sample; and
d) transferring a polarization of the short T 1 nuclei to the long T 1 nuclei within the molecules in the liquid sample by Cross Polarization via J coupling.

2. The method of claim 1 , wherein the polarizing in step b) causes a level of at least 1%, at least 5%, at least 20% or at least 50% of the short T 1 nuclei contained in the solid sample to be polarized.

3. The method of claim 1 , wherein step b) takes 30 minutes or less, 10 minutes or less or 3 minutes or less.

4. The method of claim 1 , wherein, during step c), the solid sample is dissolved in a solvent.

5. The method of claim 1 , wherein during or after step c), the solid or liquid sample is transported to a region with a lower static magnetic field as compared to a static magnetic field present during step b) and/or to a region with a higher temperature as compared to a cryogenic temperature present during step b).

6. The method of claim 5 , wherein the liquid sample is transported by pushing or pulling through a conduit by means of over-or under-pressure.

7. The method of claim 1 , wherein a longitudinal relaxation time of the long T 1 nuclei is 5 s or longer, 10 s or longer, 30 s or longer or 60 s or longer and/or a longitudinal relaxation time of the long T 1 nuclei is larger than two times, larger than five times or larger than ten times a longitudinal relaxation time of the short T 1 nuclei.

8. The method of claim 1 , wherein the long T 1 nuclei are 6 Li, 13 C, 15 N, 31 P, 29 Si, 89 Y, 57 Fe, 83 Kr, 107 Ag, 109 Ag, 115 Sn, 117 Sn, 119 Sn, 199 Hg, 129 Xe or 131 Xe and/or the short T 1 nuclei are 1 H or 19 F.

9. The method of claim 1 , wherein, in step b) for polarizing the short T 1 nuclei by Brute Force, the solid sample is exposed to a static magnetic field B 0 ≧10 T, B 0 ≧15 T or B 0 ≧20 T, wherein the solid sample is at a cryogenic temperature T cr ≦40 mK, T cr ≦20 mK or T cr ≦10 mK.

10. The method of claim 1 , wherein, in step b) for polarizing the short T 1 nuclei by DNP, the solid also includes a polarizing agent and is exposed to microwave radiation and a static magnetic field B 0 .

11. The method of claim 10 , wherein the static magnetic field B 0 ≧4.0 T or B 0 ≧6.7 T and an EPR line of a polarizing agent has a width w pa >½ω hg or W Pa >ω hg , with w pa =2√{square root over (2 log 2)}·σ, with σ 2 being a second moment of an EPR line and ω hg being a Larmor frequency of the short T 1 nuclei.

12. The method of claim 10 , wherein during a DNP in step b), the solid sample is at a cryogenic temperature T cr ≦20 K, T cr ≦10 K, T cr ≦4.2 K or T cr ≦1.5 K.

13. The method of claim 10 , wherein, during a DNP in step b), the solid sample ( 50 )is at a cryogenic temperature T cr ≧2.2 K or T cr ≧4.2 K.

14. The method of claim 10 , wherein a polarizing agent comprises nitroxyl radicals, TEMPO radicals or TEMPOL radicals.

15. The method of claim 1 , wherein, during step d), the liquid sample is at room temperature.

16. A method of magnetic resonance investigation, comprising the steps of preparing a hyperpolarized sample using the method of claim 1 , transporting the liquid sample to an NMR device or an MRI device, and measuring a magnetic resonance signal of the long T 1 nuclei of the liquid sample or measuring a magnetic resonance signal of the long T 1 nuclei for metabolic imaging.

17. An apparatus for producing a hyperpolarized sample in a magnetic resonance investigation, the apparatus comprising:
a) means for providing a solid sample, containing long T 1 nuclei and short T 1 nuclei in same molecules;
b) means for hyperpolarizing the short T 1 nuclei in the solid sample;
c) means for transforming the solid sample into a liquid sample; and
d) means for transferring a polarization of the short T 1 nuclei to the long T 1 nuclei within the molecules in the liquid sample by Cross Polarization via j coupling.

18. The apparatus of claim 17 , wherein the apparatus comprises:
a magnet or a superconducting magnet suitable for generating a static magnetic field B 0 in a polarization generation region;
a cryostat containing a sample holder for the sample in solid and liquid state, wherein the sample holder is located in the polarization generation region;
a holding chamber for the sample in liquid state, located in a polarization transfer region separate from the polarization generation region;
a first transfer conduit connecting a solvent reservoir with the sample holder;
a second transfer conduit connecting the sample holder with the holding chamber;
a field generating device suitable for generating a static magnetic field B 0 * in the polarization transfer region; and
a coil assembly or an RF coil assembly for generating an oscillating magnetic field within the holding chamber.

19. The apparatus of claim 18 , wherein, for polarizing a sample within the sample holder by DNP in the polarization generation region, the apparatus further comprising a microwave container located within the cryostat, wherein the sample holder is located within the microwave container.

20. The apparatus of claim 18 , wherein, for polarizing a sample within the sample holder by Brute Force in the polarization generation region, the apparatus further comprising a cooling means for cooling the sample holder to a cryogenic temperature T cr ≦40 mK, T cr ≦20 mK or T cr ≦10 mK, the cooling means comprising a dilution refrigerator and the magnet being suitable for generating a static magnetic field in the polarization generation region of B 0 ≧10T, B 0 ≧15 T or B 0 ≧20 T.

21. The apparatus of claim 18 , wherein the field generating device comprises one or more electro magnets or solenoidal electro magnets and/or one or more permanent magnets, separate from the magnet.

22. The apparatus of claim 18 , wherein the field generating device is at least partially included and/or integrated into the magnet, wherein the field generating device comprises one or more ferromagnetic structures coupled to the magnet or to a stray field thereof.

23. The apparatus of claim 18 , wherein the apparatus comprises a sample positioning device for placing the sample holder within the cryostat.

24. The apparatus of claim 18 , wherein the second conduit has a length between the sample container and the holding chamber of 50 cm or less, 25 cm or less or 15 cm or less.

25. The apparatus of claim 18 , wherein the holding chamber, the field generating device and the coil assembly are located within a room temperature bore of a cryostat of the magnet and above the sample holder.

Assignees

• Bruker Biospin Ag
• Ecole Polytech
• Ecole Polytechnique Fédérale De Lausanne Epfl

Inventors

• Jannin Sami
• Lohman Joost
• Bodenhausen Geoffrey
• Golman Klaes

Classifications

• G01R33/4608

  RF excitation sequences for enhanced detection, e.g. NOE, polarisation transfer, selection of a coherence transfer pathway · CPC title

• G01R33/307

  specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer · CPC title

• G01R33/282 Primary

  Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent · CPC title

• G01R33/381

  using electromagnets · CPC title