Method for creating hyperpolarization at microtesla magnetic fields

Patent metadata

Field	Value
Publication number	US-2016169998-A1
Application number	US-201514925507-A
Country	US
Kind code	A1
Filing date	Oct 28, 2015
Priority date	Oct 28, 2014
Publication date	Jun 16, 2016
Grant date	—

Abstract

Provided are methods for nuclear spin polarization enhancement via signal amplification by reversible exchange at very low magnetic fields.

First claim

What is claimed is:

1 . A method of hyperpolarizing heteronuclei, the method comprising:
(a) combining parahydrogen, a compound comprising at least one hyperpolarizable heteronucleus, and a catalyst to form a mixture; and (b) applying a magnetic field with a strength of less than 50 μT to the mixture, thereby transferring the spin order from parahydrogen to the at least one hyperpolarizable heteronucleus.

2 . The method of claim 1 , wherein the spin order is transferred during a temporary association of parahydrogen, the compound, and the catalyst while maintaining the chemical identity of the compound.

3 . The method of claim 1 , wherein the resonance frequencies of parahydrogen and the at least one hyperpolarizable heteronucleus are different.

4 . The method of claim 1 , wherein the magnetic field is determined by matching the resonance frequency of parahydrogen with the resonance frequency of at least one hyperpolarizable nucleus of the compound.

5 . The method of claim 1 , wherein the magnetic field has a strength of less than 20 μT.

6 . The method of claim 1 , wherein the magnetic field has a strength of about 0.1 to about 1 μT.

7 . The method of claim 1 , wherein the at least one heteronucleus is selected from the group consisting of 3 C, 15 N, 19 F, 29 Si, 31 P, 2 H and 29 Xe.

8 . The method of claim 1 , wherein the at least one heteronucleus is 15 N.

9 . The method of claim 1 , wherein the mixture further comprises a solvent.

10 . The method of claim 9 , wherein the solvent is a deuterated solvent.

11 . The method of claim 1 , wherein the catalyst is a heterogeneous catalyst.

12 . The method of claim 1 , wherein the catalyst is a homogeneous catalyst.

13 . The method of claim 1 , wherein the catalyst comprises a transition metal.

14 . The method of claim 13 , wherein the transition metal is iridium.

15 . The method of claim 1 , wherein the catalyst is [IrCl(COD)(IMes)].

16 . The method of claim 1 , wherein the catalyst is a homogeneous or heterogeneous catalyst, wherein the catalyst accommodates the simultaneous exchange of para-H 2 and heteronuclear spin center(s), and wherein the condition of spin-spin (weak or strong J) coupling between para-H 2 derived protons and heteronuclear spin center(s) is maintained.

17 . The method of claim 1 , wherein the compound is isotopically enriched.

18 . The method of claim 1 , wherein the compound is a contrast agent for an in vivo imaging technique.

19 . A method of performing an NMR experiment, the method comprising:
(a) combining parahydrogen, a compound comprising at least one hyperpolarizable heteronucleus, and a catalyst to form a mixture; (b) applying a magnetic field with a strength of less than 50 μT to the mixture, thereby transferring the spin order from parahydrogen to the at least one hyperpolarizable heteronucleus; and (c) performing an NMR measurement on the compound.

20 . A method of obtaining an MRI image, the method comprising:
(a) combining parahydrogen, a compound comprising at least one hyperpolarizable heteronucleus, and a catalyst to form a mixture; (b) applying a magnetic field with a strength of less than 50 μT to the mixture, thereby transferring the spin order from parahydrogen to the at least one hyperpolarizable heteronucleus; and (c) performing an MRI measurement or MR spectroscopy on the compound.

21 . A method of in vivo pH sensing, the method comprising:
(a) combining parahydrogen, a compound comprising at least one hyperpolarizable heteronucleus, and a catalyst to form a mixture; wherein the compound has at least one pKa value of about 6 to about 9; (b) applying a magnetic field with a strength of less than 50 μT to the mixture, thereby transferring the spin order from parahydrogen to the at least one hyperpolarizable heteronucleus; (c) removing the catalyst from the mixture; and (d) performing an in vivo imaging measurement on the compound.

Assignees

• Univ Duke
• Univ Vanderbilt
• Univ Southern Illinois

Inventors

• Warren Warren S
• Theis Thomas
• Chekmenev Eduard Y
• Truong Milton Y
• Coffey Aaron M
• Goodson Boyd
• Shi Fan
• Shchepin Roman V

Classifications

• A61K49/04

  X-ray contrast preparations · CPC title

• G01R33/4804

  Spatially selective measurement of temperature or pH · CPC title

• G01R33/5601 Primary

  involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent · CPC title

• G01R33/282

  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

• G01R33/445 Primary

  MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging · CPC title