Methods for detecting blood perfusion variations by magnetic resonance imaging

• US 5,190,744 A
• Filed: 03/09/1990
• Issued: 03/02/1993
• Est. Priority Date: 03/09/1990
• Status: Expired due to Term

• Current Assignee: Medrad Incorporated (Bayer AG)
• Original Assignee: Salutar, Inc. (GE Healthcare Technologies, Inc.), Regents of the University of California (University of California)
• Inventors: Kucharczyk, John, Moseley, Michael E., Rocklage, Scott M.
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/490,859
• Time in Patent Office: 1,089 Days
• Field of Search: 424/9, 436/173, 514/492, 514/184, 514/836, 324/306, 324/309, 128/653 AF, 128/653 CA, 128/654
• US Class Current: 424/9.34
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• 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 33/563 of moving material, e.g. flow contrast angiography
• CPC Class Codes: G01R 33/56308 Characterization of motion or flow; Dynamic imaging
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The invention provides a method of detecting blood flow abnormality or variation in a human or non-human body, said method comprising administering into the cardiovascular system of a said body a contrast enhancing amount of an intravascular paramagnetic metal containing magnetic resonance imaging contrast agent, subject said body to a magnetic resonance imaging procedure capable of generating from magnetic resonance signals from said body a series of temporally spaced images of at least a part of said body into which said agent passes, and detecting temporal variations in said signals or images whereby to identify regions of abnormal or modified blood flow in said body and to indicate the degree of blood flow abnormality or modification therein.

Claims

1. A method of detecting regions of blood flow abnormality or variation in a human or non-human body, said method comprising the steps of (1) administering into the cardiovascular system of said body a contrast enhancing amount of a paramagnetic metal containing magnetic resonance imaging contrast agent, (2) subjecting said body to a magnetic resonance imaging procedure and obtaining a series of temporally spaced magnetic resonance signals or images from regions in at least a part of said body into which said agent passes, (3) detecting temporal variations in said signals or images, and (4) identifying from said temporal variations in said signals or images regions of abnormal or modified blood flow in said body and providing a quantitative indication of the degree of blood flow abnormality or modification therein.

3. A method according to claim 1 wherein said contrast agent comprises a physiologically tolerable chelate complex of a paramagnetic lanthanide ion or a physiologically tolerable salt of such a chelate.

4. A method according to claim 3 wherein said contrast agent is a chelate complex of a lanthanide, or a physiologically tolerable salt thereof.

5. A method according to claim 4 wherein said contrast agent is a chelate complex of a metal ion selected from the group consisting of the paramagnetic ions of Yb, Tm, Dy, Ho, Er and Gd, or a physiologically tolerable salt thereof.

6. A method according to claim 5 wherein said contrast agent is a chelate complex of Dy(III) or a physiologically tolerable salt thereof.

7. A method according to claim 4 wherein said contrast agent comprises a physiologically tolerable non-ionic paramagnetic chelate complex.

8. A method according to claim 7 wherein said contrast agent comprises a physiologically tolerable non-ionic Dy(III) paramagnetic chelate complex.

9. A method according to claim 3 wherein said chelate complex is a complex of a linear, branched or macrocyclic chelant selected from polyaminopolycarboxylic acid chelants and from chelants wherein one or more carboxylic acid groupings are replaced with an amide, ester or hydroxamate grouping.

10. A method according to claim 9 wherein said chelate complex is a complex of a chelant selected from the group consisting of DTPA, DTPA-BMA, DOTA, D03A -and DTPA-BMO.

11. A method according to claim 5 wherein said chelate complex is a complex of a chelant selected from the group consisting of DTpA, DTpA-BMA, DOTA, DO3A, DTPA-BMO.

12. A method according to claim 11 wherein said chelate complex is DyDTPA-BMA.

13. A method according to claim 3 wherein said contrast agent is administered at a dosage of 0.02 to 3 mmol/kg bodyweight.

14. A method according to claim 13 wherein said contrast agent is administered at a dosage of 0.08 to 0.5 mmol/kg.

15. A method according to claim 1 wherein said magnetic resonance imaging procedure is a fast imaging procedure.

16. A method according to claim 15 wherein said procedure is one having an image acquisition time of less than 5 seconds.

17. A method according to claim 16 wherein said procedure is one having an image acquisition time of less than 0.5 seconds.

18. A method according to claim 17 wherein said procedure is an echo planar imaging procedure.

19. A method according to claim 1 comprising generating temporally spaced T₂ * or T₂ -weighted images.

20. A method according to claim 19 wherein said magnetic resonance imaging procedure is a spin-echo or gradient echo procedure.

21. A method according to claim 19 comprising generating and comparing T₁ -weighted images or signals transformable thereto and T₂ * or T₂ -weighted images or signals transformable thereto whereby to identify body regions in which blood perfusion occurs.

22. A method according to claim 1 being a method of detecting body regions of blood flow deficit.

23. A method according to claim 22 being a method of detecting ischemic regions.

24. A method according to claim 1 wherein said contrast agent comprises a physiologically tolerable complex of a paramagnetic transition metal ion or a physiologically tolerable salt of such a chelate.

25. The method of claim 1 wherein said magnetic resonance imaging contrast agent contains as a said metal a species having a magnetic moment of at least 4 Bohr magnetons.

26. The method of claim 1 wherein said magnetic resonance imaging agent contains as a said metal a transition metal selected from Cr, V, Mn, Fe and Co.

27. The method of claim 1 wherein said magnetic resonance imaging agent contains as a said metal a lanthanide selected from Gd, Tb, Dy, Ho, Er, Tm and Yb.

28. The method of claims 1 or 2 comprising the further step of obtaining a quantitative indication of the blood volume in said regions affected by said blood flow abnormality or modification.

29. The method of claim 28 comprising the further step of numerically evaluating the area under a curve of a plot of signal intensity change over time.

30. The method of claims 1 or 2 comprising the further steps of subjecting said body to a magnetic resonance imaging procedure in the absence of said contrast agent and obtaining a magnetic resonance signal or image from at least a part of said body to establish a native signal or image, and wherein temporal variations are detected between said native signal or image and said temporally spaced series of signals or images obtained in the presence of said contrast agent.

31. The method of claim 1 comprising the further step of detecting rates of signal intensity changes in said temporally spaced signals or images.

32. The method of claim 1 comprising the further step of detecting degrees of signal intensity changes in said temporally spaced signals or images.

33. The method of claim 32 comprising the further step of detecting durations of signal intensity changes in said temporally spaced signals or images.

34. The method of claims 1 or 2 wherein said step of obtaining a series of temporally spaced magnetic resonance signals or images further comprises obtaining signals or images from regions of normally perfused tissue in at least a part of said body to establish a reference perfusion signal or image.

35. The method of claims 1 or 2 wherein said part of said body is within the cranium.

36. The method of claims 1 or 2 wherein said part of said body is a cardiac region.

2. A method of detecting and quantitatively evaluating the severity and spatial extent of ischemic regions in a human or non-human body, said method comprising the steps of (1) administering into the cardiovascular system of said body a contrast enhancing amount of a paramagnetic metal containing magnetic susceptibility magnetic resonance imaging contrast agent, (2) subjecting said body to a magnetic resonance imaging procedure and obtaining a series of temporally spaced magnetic resonance signals or images from regions in at least a part of said body into which said agent passes, (3) detecting temporal variations in said signals or images, and (4) detecting from said temporal variations in said signals or images ischemic tissue and providing a quantitative and spatial indication of the degree of blood perfusion deficit therein.