METHOD OF IMAGING METABOLIC FUNCTION

• US 20090246138A1
• Filed: 08/24/2007
• Published: 10/01/2009
• Est. Priority Date: 08/25/2006
• Status: Active Grant

• Current Assignee: Aurum Biosciences Limited
• Original Assignee: Greater Glasgow Health Board (Scottish Government)
• Inventors: Brennan, David, Santosh, Celestine
• Granted Patent: US 9,144,392 B2
• Time in Patent Office: Days
• US Class Current: 424/9.200
• 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 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: G01R 33/54 Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
• 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: G06T 2207/30004 Biomedical image processing
• CPC Class Codes: G06T 7/0012 Biomedical image inspection

Abstract

A contrast imaging method e.g. of the T2* weighted “BOLD” type is adapted by use together with an oxygen challenge to provide imaging for the assessment of the metabolic responses of tissue over a period of time the method utilizing three components, oxygen, deoxyhaemoglobin, and oxyhaemoglobin together with time, to provide four variable parameters which allows oxygen to be used as a metabolic marker that can be utilized in an imaging evaluation of soft tissue and organs, e.g. in the study of viable tissue and organ function or dysfunction, which allows utility in diagnosis and assessment of conditions such as cancer, dementia, circulatory disorders, and autoimmune disorders.

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

ii) administering oxygen to said organism, wherein the administration of oxygen is continued for a period sufficient to convert all deoxyhaemoglobin in the plasma in the target area to oxyhaemoglobin which generates a positive imaging signal, and thereafter continued to the intent that the deoxyhaemoglobin is saturated such that administered oxygen remains free in the plasma and generates a negative imaging signal;

iii) generating imaging data in response to said administration of oxygen;

iv) processing said imaging data to obtain data relating to the relative amounts of deoxyhaemoglobin and free oxygen present in said target area following administration of the oxygen, and correlating said data to the metabolic function of the target area.

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

4. The method of claim 1, wherein the observation of a negative imaging signal after administration of free oxygen at low concentration doses indicates a low metabolic rate.

5. The method of claim 4, wherein a change in signal over time from positive to negative is used to provide information on the rate of oxidative metabolism.

13. The method of claim 1, wherein the administration of oxygen is in stages including a low level stage, and at least one stage at an elevated level in comparison with the “

low level”

stage.

14. The method of claim 13, wherein the method comprises a final low level stage or “

rest phase”

.

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

16. The method of claim 15, wherein an oxygen carrier is utilised in the intravenous delivery.

17. The method of claim 16, wherein the oxygen carrier is a physiologically inert oxygen carrier.

18. The method of claim 16, wherein the oxygen carrier is selected from the group consisting of perfluorocarbons.

19. The method of claim 18, wherein the perfluorocarbon is a stable emulsion of small particles having median diameter <

0.2 μ

m.

20. The method of claim 18, wherein the perfluorocarbon is delivered as a bolus to facilitate determination of tissue perfusion information.

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

22. 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 including epilepsy (recurrent seizure), dementia and the like progressive brain dysfunctionality, autoimmune diseases including multiple sclerosis, neoplastic soft tissue dysfunctionality including cancers of the head and neck, lung cancers, gastrointestinal cancers, genitourinary cancers, lymphoma, and melanoma.

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

40. A method of determining effects of a therapeutic agent or prophylactic agent upon soft tissue or an organ comprising the step of carrying out the method of claim 1, 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.

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24. A diagnostic molecular magnetic resonance imaging method 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 deoxyhaemoglobin and free oxygen 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.

25. The method of claim 24, wherein the oxygen is administered using a physiologically inert oxygen carrier.

26. The method of claim 24, wherein the oxygen carrier is selected from the group consisting of perfluorocarbons.

34. The method of claim 24, wherein the administration of oxygen is in stages including a low level stage, and at least one stage at an elevated level in comparison with the “

low level”

stage.

35. The method of claim 34, wherein the method comprises a final low level stage or “

rest phase”

.

36. The method of claim 24, wherein the oxygen is administered by a method selected from the group consisting of inhalation, intravenous delivery and combinations thereof.

37. The method of claim 24, wherein the imaging method comprises O₂T2* magnetic resonance image scanning.

38. The method of claim 24, 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 including epilepsy (recurrent seizure), dementia and the like progressive brain dysfunctionality, autoimmune diseases including multiple sclerosis, neoplastic soft tissue dysfunctionality including cancers of the head and neck, lung cancers, gastrointestinal cancers, genitourinary cancers, lymphoma, and melanoma.

39. The method of claim 24, wherein the metabolic function is determined and utilised in a method of differentiating tumour recurrence from tumour necrosis.

41. A method of determining effects of a therapeutic agent or prophylactic agent upon soft tissue or an organ comprising the step of carrying out the method of claim 24, 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.

27. (canceled)

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