IP Library Granted Patent US 11,156,684
Granted Patent B2
US 11,156,684 · App. 14/925,507 · Granted Oct 26, 2021

Method for creating hyperpolarization at microTesla magnetic fields

Inventors: Warren S. Warren (Durham, NC); Thomas Theis (Durham, NC); Eduard Y. Chekmenev (Brentwood, TN); Milton L. Truong (Silver Spring, MD); Aaron M. Coffey (Nashville, TN); Boyd Goodson (Carbondale, IL); Fan Shi (Energy, IL); Roman V. Shchepin (Nashville, TN)
Assignees: Duke University; Vanderbilt University; Board of Trustees of Southern Illinois University
G01R33/445G01R33/282
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 11,156,684
App. No.
14/925,507
Granted
Oct 26, 2021
Kind
B2
Abstract

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

Claims (49)

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;

(b) applying a magnetic field with a strength of about 0.1 to about 10 μT to the mixture; and

(c) directly transferring spin order from parahydrogen to the at least one hyperpolarizable heteronucleus,

wherein the application of the magnetic field and the direct transfer of spin order are without radio frequency (rf) irradiation,

wherein the at least one heteronucleus is 15 N, and

wherein the catalyst is [IrCl(COD)(IMes)].

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 about 0.1 to about 1 μT.

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

7. The method of claim 6 , wherein the solvent is a deuterated solvent.

8. The method of claim 1 , wherein the catalyst accommodates the simultaneous exchange of para-H2 and heteronuclear spin center(s), and wherein the condition of spin-spin (weak or strong J) coupling between para-H2 derived protons and heteronuclear spin center(s) is maintained.

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

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

11. 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 about 0.1 to about 10 μT to the mixture;

(c) directly transferring spin order from parahydrogen to the at least one hyperpolarizable heteronucleus; and

(d) performing an NMR measurement on the compound,

wherein the application of the magnetic field and the direct transfer of spin order are without radio frequency (rf) irradiation,

wherein the at least one heteronucleus is 15 N, and

wherein the catalyst is [IrCl(COD)(IMes)].

12. 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 about 0.1 to about 10 μT to the mixture;

(c) directly transferring spin order from parahydrogen to the at least one hyperpolarizable heteronucleus; and

(d) performing an MRI measurement or MR spectroscopy on the compound,

wherein the application of the magnetic field and the direct transfer of spin order are without radio frequency (rf) irradiation,

wherein the at least one heteronucleus is 15 N, and

wherein the catalyst is [IrCl(COD)(IMes)].

13. 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 about 0.1 to about 10 μT to the mixture;

(c) directly transferring spin order from parahydrogen to the at least one hyperpolarizable heteronucleus;

(d) removing the catalyst from the mixture; and

(e) performing an in vivo imaging measurement on the compound,

wherein the application of the magnetic field and the direct transfer of spin order are without radio frequency (rf) irradiation,

wherein the at least one heteronucleus is 15 N, and

wherein the catalyst is [IrCl(COD)(IMes)].

14. The method of claim 1 , wherein the magnetic field has a strength of about 0.1 to about 5 μT.

15. The method of claim 1 , wherein the magnetic field has a strength of about 0.1 to about 3 μT.

16. The method of claim 1 , wherein directly transferring spin order comprises J-coupling between the at least one heteronucleus and parahydrogen-derived hydrides on the catalyst, and overpopulating a spin state of the at least one heteronucleus.

17. The method of claim 1 , wherein the spin order produced on the at least one heteronucleus corresponds to I z -magnetization on the at least one heteronucleus.

18. The method of claim 1 , wherein the spin order produced on the at least one heteronucleus corresponds to alignment or anti-alignment with the magnetic field.

19. The method of claim 1 conducted inside a magnetic shield.

20. The method of claim 11 , further comprising detecting an in-phase signal of the at least one heteronucleus in the NMR measurement on the compound.

21. The method of claim 20 , further comprising detecting the in-phase signal without detecting an anti-phase signal.

Assignments (7)
CONFIRMATORY LICENSE Recorded Sep 13, 2019
From: VANDERBILT UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 050376/0223 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2016
From: WARREN, WARREN S.; THEIS, THOMAS
To: DUKE UNIVERSITY
Reel/Frame 038345/0854 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2016
From: CHEKMENEV, EDUARD Y.; TRUONG, MILTON L.; COFFEY, AARON M.; SHCHEPIN, ROMAN V.
To: VANDERBILT UNIVERSITY
Reel/Frame 038346/0047 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2016
From: GOODSON, BOYD; SHI, FAN
To: THE BOARD OF TRUSTEES OF SOUTHERN ILLINOIS UNIVERSITY
Reel/Frame 038346/0193 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2015
From: GOODSON, BOYD; SHI, FAN
To: BOARD OF TRUSTEES OF SOUTHERN ILLINOIS UNIVERSITY
Reel/Frame 037171/0483 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2015
From: WARREN, WARREN S.; THEIS, THOMAS
To: DUKE UNIVERSITY
Reel/Frame 037171/0403 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2015
From: CHEKMENEV, EDUARD Y.; TRUONG, MILTON L.; COFFEY, AARON M.; SHCHEPIN, ROMAN V.
To: VANDERBILT UNIVERSITY
Reel/Frame 037171/0432 →
Continuity (2)
Provisional Application 62069542 · Oct 28, 2014
Related Publication 20160169998A1 · Jun 16, 2016