Methods for diagnostic imaging involving the use of a contrast agent and a coronary vasodilator
View Patent ↗Improved methods for providing an image of an internal region of a patient, especially the cardiovascular region. Embodiments of the invention involve the administration to the patient of a contrast agent which comprises a vesicle composition comprising lipid or polymer vesicles and a gas or gaseous precursor, in combination with a coronary vasodilator. The patient is scanned using diagnostic imaging, such as ultrasound, to obtain a visible image of the region. The methods are particularly useful for diagnosing the presence of diseased tissue in the cardiovascular region of a patient, as well as for measuring blood flow in the cardiovascular region of a patient.
1. A method for diagnosing the presence of a disease of the coronary arteries in a patient comprising (i) administering to the patient by continuous intravenous infusion a vesicle composition comprising, in an aqueous carrier, vesicles and a gas or gaseous precursor, wherein said vesicles are selected from the group consisting of liposomes and micelles, and comprise a phospholipid selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine, 1-hexadecyl-2-palmitoylglycerophosphoethanolamine, and phosphatidic acids, (ii) scanning the patient using diagnostic imaging to obtain a visible image of the myocardium, (iii) administering to the patient a coronary vasodilator, (iv) continuing said scanning, and (v) evaluating the degree of myocardial perfusion from a videodensity versus time relationship in the images obtained in steps (ii) through (iv), wherein said vesicle composition is administered for a time period of at least about 30 seconds or longer to maintain the concentration of vesicles in the cardiovascular region at about a constant level, said constant level being of sufficient time to provide a measurement of a baseline videodensitometry.
2. A method according to claim 1 wherein said vesicles comprise unilamellar vesicles.
3. A method according to claim 2 wherein said vesicles comprise one monolayer.
4. A method according to claim 1 wherein said vesicles comprise one bilayer.
5. A method according to claim 1 wherein said vesicles are selected from the group consisting of oligolamellar and multilamellar vesicles.
6. A method according to claim 1 wherein said phosphatidic acid comprises dipalmitolylphosphatidic acid.
7. A method according to claim 1 wherein said lipid further comprises a polymer.
8. A method according to claim 7 wherein said polymer comprises a hydrophilic polymer.
9. A method according to claim 8 wherein said hydrophilic polymer comprises polyethylene glycol.
10. A method according to claim 1 wherein said gas comprises a fluorinated gas.
11. A method according to claim 10 wherein said fluorinated gas is selected from the group consisting of a perfluorocarbon, sulfur hexafluoride and heptafluoropropane.
12. A method according to claim 11 wherein said fluorinated gas comprises a perfluorocarbon.
13. A method according to claim 12 wherein said perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluorocyclobutane.
14. A method according to claim 1 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomography imaging.
15. A method according to claim 14 wherein said diagnostic imaging comprises ultrasound imaging.
16. A method according to claim 1 wherein said coronary vasodilator is selected from the group consisting of arterial vasodilators, venous vasodilators, preload reducers and preload/afterload reducers.
17. A method according to claim 16 wherein said coronary vasodilator is selected from the group consisting of nitroprusside, nitroglycerin, isosorbide dinitrate, isosorbide tetranitrate, nifedipine and dipyridamole.
18. A method according to claim 17 wherein said coronary vasodilator is dipyridamole.
19. A method according to claim 1 wherein said coronary vasodilator enhances brightness in the diagnostic image.
20. A method according to claim 1 wherein said coronary vasodilator substantially eliminates diagnostic artifacts in the diagnostic image.
21. A method according to claim 1 wherein said vesicle composition further comprises an additional bioactive agent.
22. A method according to claim 1 wherein said step of administering said vesicular composition by continuous infusion comprises the use of a constant infusion device.
23. A method according to claim 22 wherein said constant infusion device comprises a power injector.
24. A method for evaluating coronary reserve in a patient comprising (i) administering to the patient by continuous intravenous infusion a vesicle composition comprising, in an aqueous carrier, vesicles and a gas or gaseous precursor, wherein said vesicles are selected from the group consisting of liposomes and micelles, and comprise a phospholipid selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine, 1-hexadecyl-2-palmitoylglycerophosphoethanolamine, and phosphatidic acids, (ii) scanning the patient using diagnostic imaging to obtain a visible image of the myocardium, (iii) administering to the patient a coronary vasodilator, (iv) continuing said scanning, (v) evaluating the difference in myocardial perfusion from a videodensity versus time relationship in the images obtained in steps (ii) through (iv), wherein said vesicle composition is administered for a time period of at least about 30 seconds or longer to maintain the concentration of vesicles in the cardiovascular region at about a constant level, said constant level being of sufficient time to provide a measurement of a baseline videodensitometry.
25. A method according to claim 24 wherein said vesicles comprise unilamellar vesicles.
26. A method according to claim 25 wherein said vesicles comprise one monolayer.
27. A method according to claim 25 wherein said vesicles comprise one bilayer.
28. A method according to claim 24 wherein said vesicles are selected from the group consisting of oligolamellar and multilamellar vesicles.
29. A method according to claim 24 wherein said phosphatidic acid comprises dipalmitolylphosphatidic acid.
30. A method according to claim 24 wherein said lipid further comprises a polymer.
31. A method according to claim 30 wherein said polymer comprises a hydrophilic polymer.
32. A method according to claim 31 wherein said hydrophilic polymer comprises polyethylene glycol.
33. A method according to claim 24 wherein said gas comprises a fluorinated gas.
34. A method according to claim 33 wherein said fluorinated gas is selected from the group consisting of a perfluorocarbon, sulfur hexafluoride and heptafluoropropane.
35. A method according to claim 34 wherein said fluorinated gas comprises a perfluorocarbon.
36. A method according to claim 35 wherein said perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluorocyclobutane.
37. A method according to claim 24 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomography imaging.
38. A method according to claim 37 wherein said diagnostic imaging comprises ultrasound imaging.
39. A method according to claim 24 wherein said coronary vasodilator is selected from the group consisting of arterial vasodilators, venous vasodilators, preload reducers and preload/afterload reducers.
40. A method according to claim 39 wherein said coronary vasodilator is selected from the group consisting of nitroprusside, nitroglycerin, isosorbide dinitrate, isosorbide tetranitrate, nifedipine and dipyridamole.
41. A method according to claim 40 wherein said coronary vasodilator is dipyridamole.
42. A method according to claim 24 wherein said coronary vasodilator enhances brightness in the diagnostic image.
43. A method according to claim 24 wherein said coronary vasodilator substantially eliminates diagnostic artifacts in the diagnostic image.
44. A method according to claim 24 wherein said vesicle composition further comprises an additional bioactive agent.
45. A method according to claim 24 wherein said step of administering said vesicular composition by continuous infusion comprises the use of a constant infusion device.
46. A method according to claim 45 wherein said constant infusion device comprises a power injector.