Systems and methods of performing NMR spectroscopy and MRI

Patent metadata

Field	Value
Publication number	US-9566354-B2
Application number	US-201313998342-A
Country	US
Kind code	B2
Filing date	Oct 23, 2013
Priority date	Oct 23, 2012
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

A method of performing Nuclear Magnetic Resonance (NMR) spectroscopy or Magnetic Resonance Imaging (MRI). The methods may include: a) generating a compound comprising a first nuclear species (I 1 ), a second nuclear species (I 2 ), a third nuclear species (S), a heteronuclear coupling asymmetry (|J 1S −J 2S |) and a nuclear singlet state spin order localized on I 1 and I 2 ; b) transferring the nuclear singlet state spin order into heteronuclear magnetization localized on S by applying a single, non-recursive pulse sequence at a low magnetic field in the strong coupling regime of protons; and c) performing NMR spectroscopy or MRI with the compound comprising heteronuclear magnetization localized on S. The |J 1S −J 2S | may be non-zero. The pulse sequence may include a plurality of sequential radio frequency pulses separated by independent evolution interval. The pulse sequence may be capable of transferring at least about 75% of the nuclear singlet state spin order into heteronuclear magnetization localized on S at any |J 1S −J 2S | when the independent evolution intervals are optimized.

First claim

What is claimed is:

1. A method of performing Nuclear Magnetic Resonance (NMR) spectroscopy or Magnetic Resonance Imaging (MRI), the method comprising:
a) generating a compound comprising a first nuclear species (I 1 ), a second nuclear species (I 2 ), a third nuclear species (S), a heteronuclear coupling asymmetry (|J 1S −J 2S |) and a nuclear singlet state spin order localized on I 1 and I 2 ;
b) transferring the nuclear singlet state spin order into heteronuclear magnetization localized on S by applying a single, non-recursive pulse sequence at a low magnetic field in the strong coupling regime of protons; and
c) performing NMR spectroscopy or MRI with the compound comprising heteronuclear magnetization localized on S,

wherein |J 1S −J 2S | is non-zero,
wherein the pulse sequence comprises a plurality of sequential radio frequency pulses separated by independent evolution intervals,
wherein the pulse sequence transfers at least about 75% of the nuclear singlet state spin order into heteronuclear magnetization localized on S at any |J 1S −J 2S | when the independent evolution intervals are optimized, and
wherein the pulse sequence comprises the following sequential steps:
a) waiting a time t 1 after generating the compound;
b) applying a 180(+x) pulse on I 1 and I 2 ;
c) waiting a time t 2 ;
d) applying a 90(+y) pulse on S;
e) waiting a time t 3 ;
f) applying a 180(+x) pulse on I 1 and I 2 ;
g) waiting a time t 4 ; and
h) applying a 90(+x) pulse on S.

2. The method of claim 1 , wherein generating a compound comprises hyperpolarizing the compound by parahydrogen induced polarization (PHIP).

3. The method of claim 1 , wherein the compound has a Hamiltonian of
H= 2π[ J 12 ( I 1 ·I 2 )+ J 1S I 1z S z +J 2S I 2z S z ].

4. The method of claim 1 , wherein the pulse sequence comprises a first portion and a second portion, wherein the first portion converts the nuclear singlet state spin order localized on I 1 and I 2 into a pure state which is coupled to S, and wherein the second portion converts the pure state which is coupled to S into longitudinal net magnetization on S.

5. The method of claim 1 , wherein t 1 , t 2 , t 3 and t 4 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into longitudinal net magnetization on S.

6. The method of The method of claim 1 , wherein t 1 and t 2 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into a pure state which is coupled to S, and wherein t 3 and t 4 are selected to maximize transfer of the pure state which is coupled to S into longitudinal net magnetization on S.

7. The method of claim 1 , wherein the pulse sequence transfers at least about 90% of the nuclear singlet state spin order into heteronuclear magnetization localized on S at any |J 1S −J 2S | when the independent evolution intervals are optimized.

8. An NMR spectroscopy or MRI system configured to perform the method of claim 1 .

9. A method of performing Nuclear Magnetic Resonance (NMR) spectroscopy or Magnetic Resonance Imaging (MRI), the method comprising:
a) generating a compound comprising a first nuclear species (I 1 ), a second nuclear species (I 2 ), a third nuclear species (S), a heteronuclear coupling asymmetry (|J 1S −J 2S |) and nuclear singlet state spin order localized on I 1 and I 2 ;
b) transferring the nuclear singlet state spin order into heteronuclear magnetization localized on S by applying a single, non-recursive pulse sequence at a low magnetic field in the strong coupling regime of protons; and
c) performing NMR spectroscopy or MRI with the compound comprising heteronuclear magnetization localized on S,

wherein |J 1S −J 2S | is non-zero,
wherein the pulse sequence comprises a plurality of sequential radio frequency pulses separated by independent evolution intervals,
wherein the pulse sequence transfers at least about 75% of the nuclear singlet state spin order into heteronuclear magnetization localized on S at an |J 1S −J 2S | when the independent evolution intervals are optimized, and
wherein the hyperpolarized sample further comprises a fourth nuclear species (R), and wherein the pulse sequence comprises the following sequential steps:
a) waiting a time t 1 after generating the compound;
b) applying a 180(+x) pulse on S;
c) waiting a time t 2 ;
d) applying a 180(+x) pulse on I 1 and I 2 ;
e) waiting a time t 3 ;
f) applying a 90(+y) pulse on S;
g) waiting a time t 4 ;
h) applying a 180(+x) pulse on S;
i) waiting a time t 5 ;
j) applying a 180(+x) pulse on I 1 and I 2 ;
k) waiting a time t 6 ; and
l) applying a 90(+x) pulse on S.

10. The method of claim 9 , wherein t 1 , t 2 , t 3 , t 4 , t 5 and t 6 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into longitudinal net magnetization on S.

11. The method of claim 9 , wherein t 1 , t 2 and t 3 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into a pure state which is coupled to S, and wherein t 4 , t 5 and t 6 are selected to maximize transfer of the pure state which is coupled to S into longitudinal net magnetization on S.

12. A method of performing Nuclear Magnetic Resonance (NMR) spectroscopy or Magnetic Resonance Imaging (MRI), the method comprising:
a) generating a compound comprising a first nuclear species (I 1 ), a second nuclear species (I 2 ), a third nuclear species (S), a fourth nuclear species (R) and a nuclear singlet state spin order localized on I 1 and I 2 ;
b) transferring the nuclear singlet state spin order into heteronuclear magnetization localized on S by applying a pulse sequence at a low magnetic field in the strong coupling regime of protons; and
c) performing NMR spectroscopy or MRI with the compound comprising heteronuclear magnetization localized on S;

wherein the pulse sequence comprises the following sequential steps:
a) waiting a time t 1 after hyperpolarizing the sample;
b) applying a 180(+x) pulse on S;
c) waiting a time t 2 ;
d) applying a 180(+x) pulse on I 1 and I 2 ;
e) waiting a time t 3 ;
f) applying a 90(+y) pulse on S;
g) waiting a time t 4 ;
h) applying a 180(+x) pulse on S;
i) waiting a time t 5 ;
j) applying a 180(+x) pulse on I 1 and I 2 ;
k) waiting a time t 6 ; and
l) applying a 90(+x) pulse on S.

13. The method of claim 12 , wherein the compound has a Hamiltonian of
H= 2π[ J 12 ( I 1x I 2x +I 1y I 2y +I 1z I 2z )+ J 1S I 1z S z +J 1R I 1z R z +J 2S I 2z S z +J 2R I 2z R z +J SR S z R z ].

14. The method of claim 12 , wherein t 1 , t 2 , t 3 , t 4 , t 5 and t 6 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into longitudinal net magnetization on S.

15. The method of claim 12 , wherein t 1 , t 2 and t 3 are selected to maximize transfer of the nuclear singlet state spin order localized on I 1 and I 2 into a pure state which is coupled to S, and wherein t 4 , t 5 and t 6 are selected to maximize transfer of the pure state which is coupled to S into longitudinal net magnetization on S.

16. A method of performing Nuclear Magnetic Resonance (NMR) spectroscopy or Magnetic Resonance Imaging (MRI), the method comprising:
a) determining J-couplings for a compound comprising a first nuclear species (I 1 ), a second nuclear species (I 2 ), a third nu

Assignees

• Univ Vanderbilt

Inventors

• Waddell Kevin
• Cai Chong

Classifications

• A61K49/06 Primary

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• G01R33/4608 Primary

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