METHOD OF DETERMINING METABOLIC FUNCTION

• US 20120219507A1
• Filed: 09/03/2010
• Published: 08/30/2012
• Est. Priority Date: 09/04/2009
• Status: Active Grant

• Current Assignee: Aurum Biosciences Limited
• Original Assignee: Greater Glasgow Health Board (Scottish Government), University Court of the University of Glasgow (University of Glasgow)
• Inventors: Santosh, Celestine, Holmes, William, Lopez, Rosario
• Granted Patent: US 9,322,895 B2
• Time in Patent Office: Days
• US Class Current: 424/9.3
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/4076 Diagnosing or monitoring particular conditions of the nervous system A61B5/4821, A61B5/4824 take precedence
• CPC Class Codes: A61B 5/4088 Diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases or dementia
• CPC Class Codes: A61B 5/4094 Diagnosing or monitoring seizure diseases, e.g. epilepsy
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: G01N 24/08 by using nuclear magnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01N 24/088 Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics
• CPC Class Codes: G01R 33/4828 Resolving the MR signals of different chemical species, e.g. water-fat imaging
• CPC Class Codes: G01R 33/483 with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
• 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: G01R 33/5607 by reducing the NMR signal of a particular spin species, e.g. of a chemical species for fat suppression, or of a moving spin species for black-blood imaging
• CPC Class Codes: G01R 33/5617 using RF refocusing, e.g. RARE
• CPC Class Codes: G01R 33/56341 Diffusion imaging
• CPC Class Codes: G01R 33/56366 Perfusion imaging

Abstract

The present invention provides a novel lactate difference imaging (LDI) technique, allowing assessment of the metabolic responses of tissue over a period of time. This approach utilises lactate change over a time period as an indicator of viable tissue, and offers benefits in the management and treatment of the effects of many common diseases, in particular stroke.

Claims

1. A method of imaging metabolic function in a target area of an organism using contrast magnetic resonance imaging (MRI), the method comprising the steps of:

i) obtaining a first measurement of lactate in a target area of the organism;

ii) administering oxygen to said organism;

iii) obtaining a second measurement of lactate in a target area of the organism following said administration of oxygen;

iv) comparing said first and second measurements to obtain data relating to the relative amounts of lactate present in said target area before and following administration of the oxygen, and

v) correlating said data to the metabolic function of the target area.

3. The method of claim 1, wherein obtaining a measurement of lactate comprises obtaining one or more MRI images of the target area.

4. A method of imaging metabolic function in a target area of an organism using contrast magnetic resonance imaging (MRI) as claimed in claim 1, wherein the steps of obtaining first and second measurements comprise the steps of:

generating baseline imaging data of the target area of the organism;

administering oxygen to said organism;

generating imaging data in response to said administration of oxygen; and

processing said imaging data to obtain data relating to the relative amounts of lactate present in said target area following administration of the oxygen.

5. A method of imaging metabolic function in a target area of an organism using contrast magnetic resonance imaging (MRI) as claimed in claim 4 wherein the imaging data so obtained relates to an indication of the relative amount of lipid and/or lactate present in the target area, and a change in image intensity following administration of oxygen indicates utilisation of lactate in the target area of the organism.

6. The method of claim 1, further comprising an MRI sequence, characterised in that the sequence comprises a combination of tailoring pulses to reduce water and fat saturation, optimising the frequency of pulses for the imaging of lactate and utilising a rapid acquisition relaxation enhanced (RARE) imaging method for measuring the magnetic resonance in the target area.

7. The method of claim 1, wherein the method further comprises one or more MRI techniques selected from RARE T₂ imaging, diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), 1H localised spectroscopy and lactate difference imaging (LDI).

8. The method of claim 1, wherein data obtained is processed to produce a metabolic map of the target area.

9. The method of claim 1, wherein the administration of oxygen is continued for a period sufficient to remove all lactate in the target area.

10. The method of claim 1, wherein the observation of a reduction in the lactate signal after administration of free oxygen at low concentration doses indicates metabolic activity and therefore functional integrity in the target area.

11. The A method of claim 1, wherein the target area is selected from the group consisting of a region of tissue and an organ.

20. The A method of claim 1, wherein the oxygen is administered by a method selected from the group consisting of inhalation, intravenous delivery and combinations thereof.

26. The method of claim 1, wherein the imaging method comprises O₂T₂* magnetic resonance image scanning.

27. The method of claim 1, wherein the metabolic function is determined in a patient affected by a condition selected form the group consisting of circulatory disorders including stroke, neural disorders, progressive brain dysfunctionality, autoimmune diseases neoplastic soft tissue dysfunctionality, lung cancers, gastrointestinal cancers, genitourinary cancers, lymphoma, and melanoma.

28. The method of claim 1, wherein the metabolic function is determined and utilised as a means of differentiating tumour recurrence from tumour necrosis.

37. The method of claim 1 to determine effects of a therapeutic agent or prophylactic agent upon soft tissue or an organ in an organism using contrast magnetic resonance imaging (MRI), the method further comprising the steps of:

repeating steps i) to iv) in conjunction with simultaneous or sequential administration of the therapeutic agent, and evaluating the metabolic function to determine changes attributable to effects of the therapeutic agent.

38. An MRI scanner configured to carry out the method of claim 1.

39. The MRI scanner of claim 38 configured to:

i) generate baseline imaging data of the target area of an organism prior to an intervention;

ii) obtain additional imaging data of the target area of an organism following said intervention; and

iii) process said imaging data to obtain data relating to the relative amounts of lactate present in said target area following said intervention, and correlate said data to the metabolic function of the target area.

41. The MRI scanner of claim 38 further configured to execute a sequence for imaging changes in the lactate signal, comprising

i) tailoring pulses to reduce water and fat saturation,

ii) optimising the frequency of pulses for the imaging of lactate, and

iii) utilising a rapid acquisition relaxation enhanced (RARE) imaging method for measuring the magnetic resonance in the target area.

42. The MRI scanner of claim 38, further configured to perform one or more MRI techniques selected from RARE T₂ imaging, diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), 1H localised spectroscopy and lactate difference imaging (LDI).

43. The MRI scanner of claim 38, further configured to process the data obtained to produce a metabolic map of the target area.

44. The MRI scanner of claim 39, wherein the intervention is administration of oxygen.

2. (canceled)

12-19. -19. (canceled)

21-25. -25. (canceled)

29. A method of diagnostic molecular magnetic resonance imaging comprising the steps of:

a) administering oxygen to a patient whilst magnetic resonance imaging is carried out;

b) generating images of the target area of interest of the patient'"'"'s body before, during and after administration of oxygen; and

c) processing said images to obtain data relating to the relative amounts of lactate and/or lipid in said target area following administration of oxygen, said data being indicative of the metabolic function of said target area and being useful in the diagnosis of disease.

30. The method of diagnostic molecular magnetic resonance imaging as claimed in claim 29, comprising the steps of:

a) administering oxygen to a patient whilst magnetic resonance imaging is carried out;

b) generating images of the target area of interest of the patient'"'"'s body before, during and after administration of oxygen; and

c) processing said images to obtain data relating to the relative amounts of water saturation and fat saturation in said target area over time following administration of oxygen, said data being indicative of the metabolic function of said target area and being useful in the diagnosis of disease.

31. The method of claim 30 comprising the additional step of optimising the images obtained so as to reduce the signal from water saturation and fat saturation in said target area.

32-36. -36. (canceled)

40. (canceled)

45-60. -60. (canceled)