Methods for detecting blood perfusion variations by magnetic resonance imaging

• US 5,494,655 A
• Filed: 09/14/1994
• Issued: 02/27/1996
• Est. Priority Date: 03/09/1990
• Status: Expired due to Term

• Current Assignee: Medrad Incorporated (Bayer AG)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Kucharczyk, John, Rocklage, Scott M., Moseleyp, Michael E.
• Primary Examiner(s): Hollinden, Gary E.
• Application Number:
  US08/306,221
• Time in Patent Office: 531 Days
• Field of Search: 424/9.36, 424/9.363, 424/9.364, 424/9.365, 324/306, 324/309, 436/173, 128/653.4, 128/654, 128/653.3, 514/184, 514/492, 514/502, 514/836
• US Class Current: 424/9.36
• 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 monitoring the vasodilatory or vasoconstrictive effects of a physiologically active substance administered to a human or non-human animal body, said method comprising the steps of: administering said substance into said body; administering into the systemic vasculature of said body a contrast enhancing amount of an intravascular paramagnetic metal containing magnetic resonance imaging contrast agent; subjecting 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, said procedure being a fast imaging procedure having an image acquisition time of less than five seconds; and detecting temporal variations in said signals or images whereby to monitor the vasoconstriction or vasodilation induced by said substance.

Claims

1. A method of monitoring the vasodilatory or vasoconstrictive effects of a physiologically active substance administered to a human or non-human body, said method comprising the steps of:

administering said substance into said body;

administering into the systemic vasculature of said body a contrast enhancing amount of an intravascular paramagnetic metal containing magnetic resonance imaging contrast agent;

subjecting 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, said procedure being a fast imaging procedure having an image acquisition time of less than five seconds; and

detecting temporal variations in said signals or images whereby to monitor the vasoconstriction or vasodilation induced by said substance.

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

3. A method according to claim 2 wherein said contrast agent is a chelate complex of a metal ion selected from the paramagnetic ions of Yb, Tm, Dy, Ho, Er and Gd, or a physiologically tolerable salt thereof.

4. A method according to claim 3 wherein said contrast agent is a chelate complex of Dy(III) or a physiologically tolerable salt thereof.

5. A method according to claim 2 wherein said contrast agent comprises a physiologically tolerable non-ionic paramagnetic lanthanide chelate complex.

6. A method according to claim 2 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.

7. A method according to claim 6 wherein said chelate complex is a complex of a chelant selected from the group consisting of DTPA, DTPA-BMA, DOTA, Do3A, DTPA-BMO and HP-DO3A.

8. A method according to claim 2 wherein said chelate complex is DyDTPA-BMA.

9. A method according to any one of claims 1, 2, 4 or 8 wherein said contrast agent is administered at a dosage of 0.02 to 3 mmol/kg bodyweight.

10. A method according to claim 9 wherein said contrast agent is administered at a dosage of 0.08 to 0.5 mmol/kg.

11. A method according to any one of claims 1, 2, 4 or 8 wherein said procedure is one having an image acquisition time of less than 0.5 seconds.

12. A method according to any one of claims 1, 2, 4 or 8 wherein said procedure is an echo planar imaging procedure.

13. A method according to any one of claims 1, 2, 4 or 8 wherein administration of said contrast agent is by bolus injection.

14. A method according to any one of claims 1, 2, 4 or 8 comprising generating temporally spaced T₂ * or T₂ -weighted images.

15. A method according to claim 14 wherein said magnetic resonance imaging procedure is a spin-echo or gradient echo procedure.

16. A method according to claim 14 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.

17. A method according to claim 1 being a method of detecting body regions of blood flow deficit in which blood perfusion is thermally or chemically modified.

18. 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.

19. A method according to claim 8 wherein said contrast agent is administered as a contrast medium composition comprising DyDTPA-BMA and CaNaDTPA-BMA in a molar ratio of about 20:

1.

21. A method according to any one of claims 1 or 20 including the steps of identifying from said temporal variations 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.

20. A method of monitoring the vasodilatory or vasoconstrictive effects of a physiologically active substance administered to a human or non-human animal body said method comprising administering said substance into said body, administering into the systemic vasculature of said body a contrast enhancing amount of an intravascular paramagnetic metal containing magnetic susceptibility magnetic resonance imaging contrast agent, subjecting 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 monitor the vasoconstriction or vasodilation induced by said substance.