MRI compatible method and device for rapid DNP on a solid state hyperpolarized sample material

Patent metadata

Field	Value
Publication number	US-9329245-B2
Application number	US-201213443903-A
Country	US
Kind code	B2
Filing date	Apr 11, 2012
Priority date	Apr 11, 2012
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

A method for producing hyperpolarized sample material for use in magnetic resonance investigations involves preparing a target material containing high γ nuclei with a short T 1 , a polarizing agent with a broad EPR line, and low γ nuclei with a long T 1 . The polarizing agent in the target material is irradiated with microwave radiation, wherein the target material is at a cryogenic temperature and exposed to a static magnetic field B 0 ≧4.0 T, thus polarizing the high γ nuclei by DNP, and the polarization is transferred from the high γ nuclei to the low γ nuclei by Cross Polarization. A dissolved sample material is prepared containing the hyperpolarized low γ nuclei from the target material. Nuclei with a long longitudinal relaxation time T 1 can thereby be quickly hyperpolarized to a high polarization level.

First claim

We claim:

1. A method of producing hyperpolarized sample material that is utilized with magnetic resonance investigations, the method comprising the steps of:
a) disposing a target material within a sample container, the target material containing high γ nuclei having a gyromagnetic ratio γ hg with |γ hg/ 2π|≧40 MHz/T, along with a polarizing agent and low γ nuclei having a gyrornagnetic ratio γ lg with 4.3 MHz/T≦|γ lg /2π|≦18 MHz/T, the high γ nuclei having a short longitudinal relaxation time T 1 hg and the low γ nuclei having a long longitudinal relaxation time T 1 lg , wherein T 1 hg <T 1 lg ;
b) placing the sample container with the target material in a magnet, thereby exposing the target material to a static magnetic field B 0 ≧4.0 T generated by that magnet;
c) placing and keeping the sample container within a cryostat having liquid or gaseous helium, thereby maintaining the target material at a cryogenic temperature Tcr such that the target material is solid before performing step d);
d) irradiating the polarizing agent in the solid target material with microwave radiation generated by a microwave source, thereby polarizing the high γ nuclei by DNP, wherein an EPR line of the polarizing agent has a width w Pa >½ω hg , with w Pa =2√{square root over (2 log 2)}·σ, σ 2 being a second moment of the EPR line and ω hg being a Larmor frequency of the high γ nuclei;
e) subjecting the solid target material to RF radiation generated by at least one RF coil with two Larmor frequencies, thereby transferring polarization from the high γ nuclei to the low γ nuclei by Cross Polarization, wherein the solid target material is thereby disposed within the at least one RF coil; and
f) dissolving the solid target material with a dissolution device having solvents, thereby preparing a dissolved sample material from the solid target material, wherein the sample material contains hyperpolarized low γ nuclei.

2. The method of claim 1 , wherein the static magnetic field generated by the magnet of step b) is chosen with B 0 ≧4.5 T or B 0 ≧6.7 T.

3. The method of claim 1 , wherein the cryogenic temperature Tcr maintained by the cryostat of step c) is chosen with Tcr≧2.2K or Tcr≧4.2 K.

4. The method of claim 1 , wherein the cryogenic temperature Tcr maintained by the cryostat of step c) is chosen with Tcr≦10 K.

5. The method of claim 1 , wherein the cryogenic temperature Tcr maintained by the cryostat of step c) is chosen with Tcr<2.2 K, Tcr≦1.4 K or Tcr≦1.2 K.

6. The method of claim 1 , wherein the high γ nuclei and the low γ nuclei disposed within the sample container of step a) are chosen such that |γ hg /γ lg |>3.

7. The method of claim 1 , wherein the high γ nuclei disposed within the sample container of step a) are 1 H or 19 F.

8. The method of claim 1 , wherein the low γ nuclei disposed within the sample container of step a) are 6 Li, 13 C, 15 N, 31 P or 29 Si.

9. The method of claim 1 , wherein the polarization agent of step a) is selected such that w Pa ≧ω hg .

10. The method of claim 1 , wherein the polarizing agent of step a) contains nitroxyl radicals.

11. The method of claim 1 , wherein the polarizing agent of step a) contains TEMPO or TEMPOL radicals.

12. The method of claim 1 , wherein, in step d), the polarizing agent is irradiated by the microwave source until a polarization level of the high γ nuclei has reached at least 75%, at least 90% or at least 95% of a maximum achievable polarization at the static magnetic field B 0 , at the cryogenic temperature Tcr and for the applied microwave radiation.

13. The method of claim 1 , wherein the irradiation by the microwave source in step d) takes 30 minutes or less, 10 minutes or less or 3 minutes or less.

14. The method of claim 1 , wherein the long longitudinal relaxation time T 1 lg of the low γ nuclei disposed within the sample container of step a) is 5 s or longer, 10 s or longer, 30 s or longer or 60 s or longer.

15. The method of claim 1 , wherein, for the target material disposed within the sample container of step a), T 1 hg ≦½ T 1 lg , T 1 hg ≦⅕ T 1 hg or T 1 hg ≦ 1/10 T 1 lg .

16. The method of claim 1 , wherein, during irradiation by the RF coil in step e), the target material is kept in the static magnetic field B 0 generated by the magnet of step b) at the cryogenic temperature Tcr maintained by the cryostat of step c).

17. The method of claim 1 , wherein, during irradiation by the RF coil of step e), the target material is exposed to a static magnetic field lower than B 0 generated by the magnet of step b) and/or the target material is at a cryogenic temperature higher than Tcr maintained by the cryostat of step c).

18. The method of claim 1 , wherein molecules containing the low γ nuclei undergo a chemical reaction during dissolution of the target material by the dissolution device in step f).

19. The method of claim 1 , further comprising the step of subjecting the dissolved sample material containing the hyperpolarized low γ nuclei to a magnetic resonance investigation following dissolution of the target material by the dissolution device in step f).

20. The method of claim 19 , wherein the sample container, the magnet, the cryostat, the microwave source, the at least one RF coil and the dissolution device are structured such that the magnetic resonance investigation is an MRI investigation or an MRI of metabolic imaging type.

21. The method of claim 19 , wherein the sample container, the magnet, the cryostat, the microwave source, the at least one RF coil and the dissolution device are structured such that the magnetic resonance investigation is an MRS investigation or a localized MRS investigation.

22. A combined dissolution DNP and Cross Polarization device that is utilized with magnetic resonance investigations, the combined device being structured to carry out a method of producing hyperpolarized sample material, the method comprising the steps of:
a) disposing a target material within a sample container, the target material containing high γ nuclei having a gyromagnetic ratio γ hg with |γ hg /2π|≧40 MHz/T, along with a polarizing agent and low γ nuclei having a gyromagnetic ratio γ lg with 4.3 MHz/T≦|γ lg /2π|≦18 MHz/T, the high γ nuclei having a short longitudinal relaxation time T 1 hg and the low γ nuclei having a long longitudinal relaxation time T 1 lg , wherein T 1 hg <T 1 lg ;
b) placing the sample container with the target material in a magnet, thereby exposing the target material to a static magnetic field B 0 ≧4.0 T generated by that magnet;
c) placing and keeping the sample container within a cryostat having liquid or gaseous helium, thereby maintaining the target material at a cryogenic temperature Tcr such that the target material is solid before performing step d);
d) irradiating the polarizing agent in the solid target material with microwave radiation generated by a microwave source, thereby polarizing the high γ nuclei by DNP, wherein an EPR line of the polarizing agent has a width w Pa ≧ω hg with w Pa =2√{square root over (2 log 2)}·σ, σ 2 being a second moment of the EPR line and ω hg being a Larmor frequency of the high γ nuclei;
e) subjecting the solid target material to RF radiation generated by at least one RF coil with two coil with two Larmor frequencies, thereby transferring polarization from the high γ nuclei to the low γ nuclei by Cross Polarization, wherein the solid target material is thereby disposed within the at least one RF coil; and

Assignees

• Jannin Sami
• Gianotti Antonio Giuseppe
• Lohman Joost
• Engelke Frank
• Melzi Roberto
• Bornet Aurélien
• Bodenhausen Geoffrey
• Bruker Biospin Ag
• Ecole Polytechnique Fédérale De Lausanne Epfl

Inventors

• Jannin Sami
• Gianotti Antonio Giuseppe
• Lohman Joost
• Engelke Frank
• Melzi Roberto
• Bornet Aurélien
• Bodenhausen Geoffrey

Classifications

• 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

• G01R33/4608

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

• G01R33/62

  using double resonance (G01R33/24 takes precedence) · CPC title

• G01R33/5605

  by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE] · CPC title