MR-method for the in vivo measurement of temperature or pH-value by means of a hyperpolarised contrast agent

• US 7,251,519 B2
• Filed: 04/12/2001
• Issued: 07/31/2007
• Est. Priority Date: 04/14/2000
• Status: Expired due to Term

• Current Assignee: Oxford Instruments Molecular Biotools Ltd. (Oxford Instruments PLC)
• Original Assignee: GE Healthcare As (GE Healthcare Technologies, Inc.)
• Inventors: Axelsson, Oskar, Petersson, Stefan, Ardenkjaer-Larsen, Jan Henrik, Leunbach, Ib, Mansson, Sven
• Primary Examiner(s): Casler; Brian L.
• Assistant Examiner(s): Roy; Baisakhi
• Application Number:
  US10/240,754
• Publication Number:
  US 20030124732A1
• Time in Patent Office: 2,301 Days
• Field of Search: 324/300, 324307-309, 324/315, 600/410, 600/412, 600/420, 600/431, 600/407, 424/9.3, 424/9.32, 424/9.36, 436/173
• US Class Current: 600/410
• CPC Class Codes: G01R 33/4804 Spatially selective measurement of temperature or pH
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention provides a method of MR investigation of a sample, said method comprising: (i) nuclear spin polarizing a high T1 MR imaging agent which contains in its molecular structure at least two hyperpolarisable nuclei within the same molecule, the frequency difference between the two resonance lines from said nuclei, δυ, being dependent upon either the temperature or the pH of said sample; (ii) administering the nuclear spin polarized MR imaging agent to said sample; (iii) exposing said sample to a radiation at a frequency selected to excite nuclear spin transitions in said MR imaging agent; and (iv) detecting and manipulating magnetic resonance signals from said sample using a single-shot RARE acquisition sequence with shifted data acquisition.

Claims

1. A method of MR investigation of a sample, said method comprising:

(i) nuclear spin polarising a MR imaging agent, wherein said agent is a high T₁ agent and contains in its molecular structure at least two hyperpolarisable nuclei of the same type of MR imaging nuclei within the same molecule, having similar signal amplitudes, and wherein the frequency difference between the two resonance lines from said nuclei, δ

υ

, is dependent upon either the temperature, pH, pO₂, pCO₂, or ionic concentration of said sample;

(ii) administering the nuclear spin polarised MR imaging agent to said sample;

(iii) exposing said sample to a radiation at a frequency selected to excite nuclear spin transitions in selected nuclei therein;

(iv) detecting and manipulating magnetic resonance signals from said sample using a single-shot RARE acquisition sequence with shifted data acquisition, and wherein and excitation and detection steps iii) and iv) are such that said nuclei are all being excited and detected in the same sequence; and

(v) optionally generating an image, dynamic flow data, diffusion data or physiological and/or metabolic data from said detected signals.

2. A method as claimed in claim 1 wherein said hyperpolarisable nuclei in said high T₁ agent are two non-hydrogen spin ½

nuclei.

3. A method as claimed in claim 2 wherein said nuclei are two ¹³C nuclei.

4. A method as claimed in claim 1 wherein said administration in step ii) is by bolus injection.

5. A method as claimed in claim 1 wherein said administration in step ii) is after said agent has undergone dissolution in a physiologically tolerable solvent.

6. A method as claimed in claim 1 wherein said administration in step ii) is after said agent is separated from some or all of the species providing the nuclear spin polarisation to said agent.

7. A method as claimed in claim 6 wherein at least 80% of the polarisation transferring material is removed.

8. A method as claimed in claim 1 wherein said radiation in step iii) is at a frequency selected to excite nuclear spin transitions in the spin polarised nuclei of said MR imagining agent.

9. A method as claimed in claim 1 wherein said high T₁ agent is water soluble.

10. A method as claimed in claim 1, wherein said T₁ value is 100 secs or more.

11. A method as claimed in claim 1, wherein said high T₁ agent contains said hyperpolarisable nuclei in an amount greater that isotopic abundance.

12. A method as claimed in claim 1 wherein δ

υ

is dependent upon either the temperature or pH of the sample.

13. A method as claimed in claim 12 wherein said frequency difference in step i) is greater that 0.5 Hz per K or per 0.1 pH unit.

14. A method as claimed in claim 12 wherein said frequency difference in step i) is between 10 Hz and 50 Hz per K or per 0.1 pH unit.

15. A method as claimed in claim 1, wherein said MR imaging agent comprises ¹³C nuclei at two particular positions in an amount in excess of natural abundance and wherein the ¹³C nuclei amounts to ≧

2% of all carbon atoms in the agent.

16. A method as claimed in claim 15 wherein said ¹³C nuclei are present in said agent at said positions to a level of enrichment in excess of 99%.

17. A method as claimed in claim 15, wherein said agent is ³C enriched at carbonyl or quaternary carbon positions.

19. A method as claimed in claim 1 wherein the said at least two hyperpolarisable nuclei of the same type of MR imaging nuclei within the same molecule have the same signal amplitude.

18. A method as claimed in 15, wherein said ¹³C nuclei are surrounded by one or more non-MR active nuclei.

20. A method of MR investigation of a sample previously administered with a nuclear spin polarised MR imaging agent formed by nuclear spin polarising a MR imaging agent, wherein said agent is a high T₁ agent and contains in its molecular structure at least two hyperpolarisable nuclei of the same type of MR imaging nuclei within the same molecule having similar signal amplitudes, and wherein the frequency difference between the two resonance lines from said nuclei, δ

υ

, is dependent upon either the temperature, pH, pO2, pCO2 or ionic concentration of said sample, said method comprising;

i) exposing said sample to a radiation at a frequency selected to excite nuclear spin transitions in selected nuclei therein;

ii) detecting and manipulating magnetic resonance signals from said sample using a single-shot RARE acquisition sequence with shifted data acquisition, and wherein the exposing and detecting steps are such that said nuclei are all being excited and detected in the same sequence; and

iii) optionally generating an image, dynamic flow data, diffusion data or physiological and/or metabolic data from said detected signals.