CA2256592A1 - Improved methods for diagnostic imaging by regulating the administration rate of a contrast agent - Google Patents

Improved methods for diagnostic imaging by regulating the administration rate of a contrast agent

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Publication number
CA2256592A1
CA2256592A1 CA002256592A CA2256592A CA2256592A1 CA 2256592 A1 CA2256592 A1 CA 2256592A1 CA 002256592 A CA002256592 A CA 002256592A CA 2256592 A CA2256592 A CA 2256592A CA 2256592 A1 CA2256592 A1 CA 2256592A1
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Prior art keywords
gas
lipid
gaseous precursor
composition
vesicles
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Application number
CA002256592A
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French (fr)
Other versions
CA2256592C (en
Inventor
Evan C. Unger
Terry O. Matsunaga
Thomas A. Fritz
Varada Rajan Ramaswami
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lantheus Medical Imaging Inc
Original Assignee
Imarx Pharmaceutical Corp.
Evan C. Unger
Terry O. Matsunaga
Thomas A. Fritz
Varada Rajan Ramaswami
Dupont Contrast Imaging Inc.
Bristol-Myers Squibb Medical Imaging, Inc.
Lantheus Medical Imaging, Inc.
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Application filed by Imarx Pharmaceutical Corp., Evan C. Unger, Terry O. Matsunaga, Thomas A. Fritz, Varada Rajan Ramaswami, Dupont Contrast Imaging Inc., Bristol-Myers Squibb Medical Imaging, Inc., Lantheus Medical Imaging, Inc. filed Critical Imarx Pharmaceutical Corp.
Publication of CA2256592A1 publication Critical patent/CA2256592A1/en
Application granted granted Critical
Publication of CA2256592C publication Critical patent/CA2256592C/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/788—Of specified organic or carbon-based composition
    • Y10S977/797—Lipid particle
    • Y10S977/798—Lipid particle having internalized material
    • Y10S977/799—Containing biological material
    • Y10S977/801—Drug
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/927—Diagnostic contrast agent
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/927—Diagnostic contrast agent
    • Y10S977/928—X-ray agent
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/927—Diagnostic contrast agent
    • Y10S977/929—Ultrasound contrast agent
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/927—Diagnostic contrast agent
    • Y10S977/93—MRI contrast agent

Abstract

Methods for providing an image of an internal region of a patient. Embodiments of the methods involve administering to the patient a contrast agent which comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers. The patient is scanned using diagnostic imaging, such as ultrasound, to obtain a visible image of the region.
The contrast agent is administered to the patient at a rate to substantially eliminate diagnostic artifacts in the image. The methods are particularly useful for diagnosing the presence of any diseased tissue in the patient.

Claims (411)

1. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said vesicle composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in the image.
2. A method according to Claim 1 wherein said vesicles comprise lipids.
3. A method according to Claim 2 wherein said vesicle composition comprises vesicles selected from the group consisting of micelles and liposomes.
4. A method according to Claim 2 wherein said lipids comprise phospholipids.
5. A method according to Claim 4 wherein said phospholipids are selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
6. A method according to Claim 5 wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine.
7. A method according to Claim 6 wherein said phosphatidylcholine comprises dipalmitoylphosphatidylcholine.
8. A method according to Claim 5 wherein said phosphatidylethanolamine, is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine and1-hexadecyl-2-palmitoylglycerophosphoethanolamine.
9. A method according to Claim 8 wherein said phosphatidylethanolamine, comprises dipalmitoylphosphatidylethanolamine.
10. A method according to Claim 5 wherein said phosphatidic acid comprises dipalmitolylphosphatidic acid.
11. A method according to Claim 2 wherein said lipid further comprises a polymer.
12. A contrast agent according to Claim 11 wherein said polymer comprises a hydrophilic polymer.
13. A method according to Claim 11 wherein said hydrophilic polymer comprises polyethylene glycol.
14. A method according to Claim 1 wherein said vesicles comprise proteins.
15. A method according to Claim 14 wherein said proteins comprise albumin.
16. A method according to Claim 1 wherein said vesicles comprise polymers.
17. A method according to Claim 16 wherein said polymers comprise synthetic polymers or copolymers which are prepared from monomers selected from the group consisting of acrylic acid, methacrylic acid, ethyleneimine, crotonic acid, acrylamide, ethyl acrylate, methyl methacrylate, 2-hydroxyethyl methacrylate, lactic acid, glycolic acid, .epsilon.-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, ethylene glycol, hydroxyalkylmethacrylates, N-substituted acrylamides, N-substituted methacrylamides, N-vinyl-2-pyrrolidone, 2,4-pentadiene-1-ol, vinyl acetate, acrylonitrile, styrene, p-aminostyrene, p-aminobenzylstyrene, sodium styrene sulfonate, sodium 2-sulfoxyethylmethacrylate, vinyl pyridine, aminoethyl methacrylates and 2-methacryloyloxytrimethyl-ammonium chloride.
18. A method according to Claim 16 wherein said polymers comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(.epsilon.-caprolactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate and polystyrene-polyacrylonitrile.
19. A method according to Claim 18 wherein said polymers comprise polyvinylidene-polyacrylonitrile copolymer.
20. A method according to Claim 1 wherein said gas comprises a fluorinated gas.
21. A method according to Claim 20 wherein said fluorinated gas is selected from the group consisting of a perfluorocarbon, sulfur hexafluoride andheptafluoropropane.
22. A method according to Claim 21 wherein said fluorinated gas comprises a perfluorocarbon.
23. A method according to Claim 22 wherein said perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluorocyclobutane.
24. A method according to Claim 1 wherein said gaseous precursor has a boiling point of greater than about 37°C.
25. A method according to Claim 24 wherein said gaseous precursor comprises a fluorinated compound.
26. A method according to Claim 25 wherein said fluorinated compound comprises a perfluorocarbon.
27. A method according to Claim 26 wherein said perfluorocarbon is selected from the group consisting of perfluoropentane and perfluorohexane.
28. A method according to Claim 1 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomographyimaging.
29. A method according to Claim 28 wherein said diagnostic imaging comprises ultrasound imaging.
30. A method according to Claim 1 wherein said internal region comprises the heart region.
31. A method according to Claim 1 wherein said vesicle composition is administered to the patient at a rate of from about 1 x 10 6 to less than about 8 x 10 6 vesicles/Kg-sec.
32. A method according to Claim 31 wherein said vesicle composition is administered at a rate of from about 1 x 10 6 to about 7 x 10 6 vesicles/Kg-sec.
33. A method according to Claim 32 wherein said vesicle composition is administered at a rate of from about 1.5 x 10 6 to about 6 x 10 6 vesicles/Kg-sec.
34. A method according to Claim 33 wherein said vesicle composition is administered at a rate of from about 2 x 10 6 to about 5.5 x 10 6 vesicles/Kg-sec.
35. A method according to Claim 34 wherein said vesicle composition is administered at a rate of from about 2.5 x 10 6 to about 5 x 10 6 vesicles/Kg-sec.
36. A method according to Claim 35 wherein said vesicle composition is administered at a rate of from about 3 x 10 6 to about 4.5 x 10 6 vesicles/Kg-sec.
37. A method according to Claim 1 wherein said vesicle composition is administered to the patient at a rate of from about 1 x 10-7 to about 3 x 10-3 CC gas/Kg-sec.
38. A method according to Claim 37 wherein said vesicle composition is administered at a rate of from about 3 x 10-6 to about 3 x 10-3 cc gas/Kg-sec.
39. A method according to Claim 38 wherein said vesicle composition is administered at a rate of from about 4 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
40. A method according to Claim 39 wherein said vesicle composition is administered at a rate of from about 8 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
41. A method according to Claim 40 wherein said vesicle composition is administered at a rate of from about 1 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
42. A method according to Claim 41 wherein said vesicle composition is administered at a rate of from about 4 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
43. A method according to Claim 42 wherein said vesicle composition is administered at a rate of from about 8 x 10-5 to less than about 1 x 10-3 cc gas/Kg-sec.
44. A method according to Claim 43 wherein said vesicle composition is administered at a rate of from about 1 x 10-4 to about 9 x 10-4 cc gas/Kg-sec.
45. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a lipid composition comprising, in an aqueous carrier, a lipid and a gas or gaseous precursor, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said lipid composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in the image.
46. A method according to Claim 43 wherein said lipid comprises a phospholipid.
47. A method according to Claim 46 wherein said phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
48. A method according to Claim 47 wherein said lipid composition comprises a vesicle composition.
49. A method according to Claim 48 wherein said vesicle composition comprises vesicles selected from the group consisting of micelles and liposomes.
50. A method according to Claim 45 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomographyimaging.
51. A method according to Claim 50 wherein said diagnostic imaging comprises ultrasound imaging.
52. A method according to Claim 45 wherein said lipid composition is administered to the patient at a rate of from about 1 x 10-7 to about 3 x 10-3 cc gas/Kg-sec.
53. A method according to Claim 52 wherein said lipid composition is administered at a rate of from about 3 x 10-6 to about 3 x 10-3 cc gas/Kg-sec.
54. A method according to Claim 53 wherein said lipid composition is administered at a rate of from about 4 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
55. A method according to Claim 54 wherein said lipid composition is administered at a rate of from about 8 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
56. A method according to Claim 55 wherein said lipid composition is administered at a rate of from about 1 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
57. A method according to Claim 56 wherein said lipid composition is administered at a rate of from about 4 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
58. A method according to Claim 57 wherein said lipid composition is administered at a rate of from about 8 x 10-5 to less than about 1 x 10-3 cc gas/Kg-sec.
59. A method according to Claim 58 wherein said lipid composition is administered at a rate of from about 1 x 10-4 to about 9 x 10-4 cc gas/Kg-sec.
60. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
61. A method accroding to Claim 60 wherien said vesicles comprise lipids.
62. A method according to Claim 60 wherein said lipids comprise phospholipids.
63. A method according to Claim 62 wherein said phospholipids are selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
64. A method according to Claim 63 wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine.
65. A method according to Claim 64 wherein said phosphatidylcholine comprises dipalmitoylphosphatidylcholine.
66. A method according to Claim 63 wherein said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine and1-hexadecyl-2-palmitoylglycerophosphoethanolamine..
67. A method according to Claim 66 wherein said phosphatidylethanolamine comprises dipalmitoylphosphatidylethanolamine.
68. A method according to Claim 63 wherein said phosphatidic acid comprises dipalmitolylphosphatidic acid.
69. A method according to Claim 60 wherein said vesicles comprise proteins.
70. A method according to Claim 69 wherein said proteins comprise albumin.
71. A method according to Claim 60 wherein said vesicles comprise polymers.
72. A method according to Claim 71 wherein said polymers comprise synthetic polymers or copolymers which are prepared from monomers selected from the group consisting of acrylic acid, methacrylic acid, ethyleneimine, crotonic acid, acrylamide, ethyl acrylate, methyl methacrylate, 2-hydroxyethyl methacrylate, lactic acid, glycolic acid, .epsilon.-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, ethylene glycol, hydroxyalkylmethacrylates, N-substituted acrylamides, N-substituted methacrylamides, N-vinyl-2-pyrrolidone, 2,4-pentadiene-1-ol, vinyl acetate, acrylonitrile, styrene, p-amino-styrene, p-aminobenzylstyrene, sodium styrene sulfonate, sodium 2-sulfoxyethylmethacrylate, vinyl pyridine, aminoethyl methacrylates and 2-methacryloyloxytrimethylammonium chloride.
73. A method according to Claim 71 wherein said polymers comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(.epsilon.-caprolactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate and polystyrene-polyacrylonitrile.
74. A method according to Claim 73 wherein said polymers comprise polyvinylidene-polyacrylonitrile copolymer.
75. A method according to Claim 60 wherein said vesicle composition is flushed with a saline solution.
76. A method according to Claim 60 wherein said gas comprises a fluorinated gas.
77. A method according to Claim 76 wherein said fluorinated gas is selected from the group consisting of a perfluorocarbon gas, sulfur hexafluoride and heptafluoropropane.
78. A method according to Claim 77 wherein said fluorinated gas comprises a perfluorocarbon.
79. A method according to Claim 78 wherein said perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluorocyclobutane.
80. A method according to Claim 60 wherein said gaseous precursor has a boiling point of greater than about 37°C.
81. A method according to Claim 80 wherein said gaseous precursor comprises a fluorinated compound.
82. A method according to Claim 81 wherein said fluorinated compound comprises a perfluorocarbon.
83. A method according to Claim 82 wherein said perfluorocarbon is selected from the group consisting of perfluoropentane and perfluorohexane.
84. A method according to Claim 61 wherein said vesicle composition comprises vesicles selected from the group consisting of micelles and liposomes.
85. A method according to Claim 60 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomographyimaging.
86. A method according to Claim 85 wherein said diagnostic imaging comprises ultrasound imaging.
87. A method according to Claim 60 wherein said internal region comprises the heart region.
88. A method according to Claim 60 wherein said vesicle composition is flushed at a rate of from about 0.01 to about 2.4 mL/sec.
89. A method according to Claim 88 wherein said vesicle composition is flushed at a rate of from about 0.05 to about 2 mL/sec.
90. A method according to Claim 89 wherein said vesicle composition is flushed at a rate of from about 0.07 to about 1.8 mL/sec.
91. A method according to Claim 90 wherein said vesicle composition is flushed at a rate of from about 0.09 to about 1.6 mL/sec.
92. A method according to Claim 91 wherein said vesicle composition is flushed at a rate of from about 0.1 to about 1.5 mL/sec.
93. A method according to Claim 92 wherein said vesicle composition is flushed at a rate of from about 0.3 to about 1.3 mL/sec.
94. A method according to Claim 93 wherein said vesicle composition is flushed at a rate of from about 0.5 to about 1.1 mL/sec.
95. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a lipid composition comprising, in an aqueous carrier, a lipid and a gas or gaseous precursor, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
96. A method according to Claim 95 wherein said lipid comprises a phospholipid.
97. A method according to Claim 96 wherein said phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
98. A method according to Claim 97 wherein said lipid composition comprises a vesicle composition.
99. A method according to Claim 95 wherein said vesicle composition comprises vesicles selected from the group consisting of micelles and liposomes.
100. A method according to Claim 95 wherein said diagnostic imaging is selected from the group consisting of ultrasound imaging and computed tomographyimaging.
101. A method according to Claim 90 wherein said diagnostic imaging comprises ultrasound imaging.
102. A method according to Claim 95 wherein said internal region comprises the heart region.
103. A method according to Claim 95 wherein said composition is flushed at a rate of from about 0.01 to about 2.4 mL/sec.
104. A method according to Claim 103 wherein said lipid composition is flushed at a rate of from about 0.05 to about 2 mL/sec.
105. A method according to Claim 104 wherein said lipid composition is flushed at a rate of from about 0.07 to about 1.8 mL/sec.
106. A method according to Claim 105 wherein said lipid composition is flushed at a rate of from about 0.09 to about 1.6 mL/sec.
107. A method according to Claim 106 wherein said lipid composition is flushed at a rate of from about 0.1 to about 1.5 mL/sec.
108. A method according to Claim 107 wherein said lipid composition is flushed at a rate of from about 0.3 to about 1.3 mL/sec.
109. A method according to Claim 108 wherein said lipid composition is flushed at a rate of from about 0.5 to about 1.1 mL/sec.
110. A method for substantially eliminating diagnostic artifacts in a diagnostic image of an internal region of a patient comprising regulating the rate at which a contrast agent is administered to the patient.
111. A method according to Claim 110 wherein the diagnostic image is selected from the group consisting of ultrasound images and computed tomography images.
112. A method according to Claim 111 wherein the diagnostic image comprises ultrasound images.
113. A method according to Claim 110 wherein the diagnostic artifacts are selected from the group consisting of ultrasound artifacts and computed tomography artifacts.
114. A method according to Claim 113 wherein the diagnostic artifacts comprise ultrasound artifacts.
115. A method according to Claim 110 wherein said contrast agent comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers.
116. A method according to Claim 115 wherein said vesicles comprise lipids.
117. A method according to Claim 116 wherein said vesicle composition comprises vesicles selected from the group consisting of micelles and liposomes.
118. A method according to Claim 116 wherein said lipids comprise phospholipids.
119. A method according to Claim 118 wherein said phospholipids are selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
120. A method according to Claim 119 wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine.
121. A method according to Claim 120 wherein said phosphatidylcholine comprises dipalmitoylphosphatidylcholine.
122. A method according to Claim 119 wherein said phosphatidyl-ethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanol-amine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine and 1-hexadecyl-2-palmitoylglycerophosphoethanolamine.
123. A method according to Claim 122 wherein said phosphatidylethanolamine comprises dipalmitoylphosphatidylethanolamine.
124. A method according to Claim 119 wherein said phosphatidic acid comprises dipalmitolylphosphatidic acid.
125. A method according to Claim 116 wherein said lipid further comprises a polymer.
126. A contrast agent according to Claim 125 wherein said polymer comprises a hydrophilic polymer.
127. A method according to Claim 126 wherein said hydrophilic polymer comprises polyethylene glycol.
128. A method according to Claim 115 wherein said vesicles comprise proteins.
129. A method according to Claim 128 wherein said proteins comprise albumin.
130. A method according to Claim 115 wherein said vesicles comprise polymers.
131. A method according to Claim 130 wherein said polymers comprise synthetic polymers or copolymers which are prepared from monomers selected from the group consisting of acrylic acid, methacrylic acid, ethyleneimine, crotonic acid, acrylamide, ethyl acrylate, methyl methacrylate, 2-hydroxyethyl methacrylate, lactic acid, glycolic acid, .epsilon.-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, ethylene glycol, hydroxyalkylmethacrylates, N-substituted acrylamides, N-substituted methacrylamides, N-vinyl-2-pyrrolidone, 2,4-pentadiene-1-ol, vinyl acetate, acrylonitrile, styrene, p-amino-styrene, p-aminobenzylstyrene, sodium styrene sulfonate, sodium 2-sulfoxyethyl-methacrylate, vinyl pyridine, aminoethyl methacrylates and 2-methacryloyloxytrimethyl-ammonium chloride.
132. A method according to Claim 130 wherein said polymers comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(.epsilon.-caprolactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate and polystyrene-polyacrylonitrile.
133. A method according to Claim 132 wherein said polymers comprise polyvinylidene-polyacrylonitrile copolymer.
134. A method according to Claim 115 wherein said vesicle composition is administered to the patient at a rate of from about 1 x 10 6 to less than about 8 x 10 6 vesicles/Kg-sec.
135. A method according to Claim 134 wherein said vesicle composition is administered at a rate of from about 1 x 10 6 to about 7 x 10 6 vesicles/Kg-sec.
136 A method according to Claim 135 wherein said vesicle composition is administered at a rate of from about 1.5 x 10 6 to about 6 x 10 6 vesicles/Kg-sec.
137. A method according to Claim 136 wherein said vesicle composition is administered at a rate of from about 2 x 10 6 to about 5.5 x 10 6 vesicles/Kg-sec.
138. A method according to Claim 137 wherein said vesicle composition is administered at a rate of from about 2.5 x 10 6 to about 5 x 10 6 vesicles/Kg-sec.
139. A method according to Claim 138 wherein said vesicle composition is administered at a rate of from about 3 x 10 6 to about 4.5 x 10 6 vesicles/Kg-sec.
140. A method according to Claim 115 wherein said vesicle composition is administered to the patient at a rate of from about 1 x 10-7 to about 3 x 10-3 cc gas/Kg-sec.
141. A method according to Claim 140 wherein said vesicle composition is administered at a rate of from about 3 x 10-6 to about 3 x 10-3 cc gas/Kg-sec.
142. A method according to Claim 141 wherein said vesicle composition is administered at a rate of from about 4 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
143. A method according to Claim 142 wherein said vesicle composition is administered at a rate of from about 8 x 10-6 to about 2 x 10-3 cc gas/Kg-sec.
144. A method according to Claim 143 wherein said vesicle composition is administered at a rate of from about 1 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
145. A method according to Claim 144 wherein said vesicle composition is administered at a rate of from about 4 x 10-5 to about 1 x 10-3 cc gas/Kg-sec.
146. A method according to Claim 145 wherein said vesicle composition is administered at a rate of from about 8 x 10-5 to less than about 1 x 10-3 cc gas/Kg-sec.
147. A method according to Claim 146 wherein said vesicle composition is administered at a rate of from about 1 x 10-4 to about 9 x 10-4 cc gas/Kg-sec.
148. A method according to Claim 100 wherein said administration also comprises flushing said contrast agent.
149. A method according to Claim 148 wherein said contrast agent is flushed at a rate of administered to the patient at a rate of from about 1 x 10-7 to about 3 x 10-3 cc gas/Kg-sec.
150. A method according to Claim 149 wherein said contrast agent is flushed at a rate of from about 0.05 to about 2 mL/sec.
151. A method according to Claim 150 wherein said contrast agent is flushed at a rate of from about 0.07 to about 1.8 mL/sec.
152. A method according to Claim 151 wherein said contrast agent is flushed at a rate of from about 0.09 to about 1.6 mL/sec.
153. A method according to Claim 152 wherein said contrast agent is flushed at a rate of from about 0.1 to about 1.5 mL/sec.
154. A method according to Claim 153 wherein said contrast agent is flushed at a rate of from about 0.3 to about 1.3 mL/sec.
155. A method according to Claim 154 wherein said contrast agent is flushed at a rate of from about 0.5 to about 1.1 mL/sec.
156. A method according to Claim 100 wherein the region comprises the heart region.
157. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said vesicle composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in said image.
158. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a lipid composition comprising, in an aqueous carrier, a lipid and a gas or gaseous precursor, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said lipid composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in said image.
159. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said vesicle composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
160. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a lipid composition comprising. in an aqueous carrier, a lipid and a gas or gaseous precursor, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said lipid composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
161. A system for administering a contrast agent to a patient comprising:
(a) a first vessel containing a contrast agent;
(b) a second vessel containing a flushing agent;
(c) a conduit having means for directing fluid into a blood vessel of the patient;
(d) means for placing said first and second vessels into flow communication with said conduit;
(e) first flow inducing means for inducing said contrast agent to flow from said first vessel into said conduit; and (f) second flow inducing means for inducing said flushing agent to flow from said second vessel into said conduit subsequent to said flowing of said contrast agent into said conduit by said first flow inducing means.
162. A system according to Claim 161 wherein said second flow inducing means further comprises means for inducing said contrast agent to flow from said conduit into said blood vessel and for subsequently inducing said flushing agent to flow from said conduit into said blood vessel.
163. A system according to Claim 162 wherein said second flow inducing means has means for inducing flow at variable rates, whereby said contrast agent flows into said blood vessel at a first rate and said flushing agent flows into said blood vessel at a second rate.
164. A system according to Claim 161 wherein said first flow inducing means comprises a syringe plunger and said first vessel comprises a syringe barrel in which said plunger slides.
165. A system according to Claim 161 wherein said second flow inducing means comprises a mechanical injector.
166. A system according to Claim 165 wherein said mechanical injector operates using pneumatic or hydraulic pressure.
167. A system according to Claim 161 wherein said conduit comprises a needle.
168. A system according to Claim 161 wherein said conduit comprises tubing.
169. A system according to Claim 161 wherein said means for placing said first and second vessels into flow communication with said conduit comprises a three-way stopcock.
170. A system according to Claim 161 wherein said means for placing said first and second vessels into flow communication with said conduit comprises a port.
171. A system according to Claim 161 wherein said contrast agent comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers.
172. A system according to Claim 161 wherein said contrast agent comprises a lipid composition comprising, in an aqueous carrier, a lipid and a gas or gaseous precursor.
173. A system according to Claim 161 wherein said flushing agent comprises a saline solution.
174. A method according to Claim 2 wherein said vesicles comprise lipid-coated bubbles.
175. A method according to Claim 174 wherein said vesicles are selected from the group consisting of unilamellar vesicles, oligolamellar vesicles and multilamellar vesicles.
176. A method according to Claim 175 wherein said vesicles comprise unilamellar vesicles.
177. A method according to Claim 176 wherein said vesicles comprise one monolayer.
178. A method according to Claim 177 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
179. A method according to Claim 177 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
180. A method according to Claim 177 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
181. A method according to Claim 176 wherein said vesicles comprise one bilayer.
182. A method according to Claim 181 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
183. A method according to Claim 181 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
184. A method according to Claim 181 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
185. A method according to Claim 175 wherein said vesicles are selected from the group consisting of oligolamellar vesicles and multilamellar vesicles.
186. A method according to Claim 185 wherein said vesicles comprise one monolayer.
187. A method according to Claim 186 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
188. A method according to Claim 186 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
189. A method according to Claim 186 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
190. A method according to Claim 185 wherein said vesicles comprise one bilayer.
191. A method according to Claim 190 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
192. A method according to Claim 190 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
193. A method according to Claim 190 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
194. A method according to Claim 45 wherein said lipid is selected from the group consisting of unilamellar lipids, oligolamellar lipids or multilamellar lipids.
195. A method according to Claim 194 wherein said lipid is a unilamellar lipid.
196. A method according to Claim 195 wherein said unilamellar lipid comprises one monolayer.
197. A method according to Claim 196 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
198. A method according to Claim 196 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
199. A method according to Claim 196 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
200. A method according to Claim 196 wherein said lipid comprises one bilayer.
201. A method according to Claim 200 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
202. A method according to Claim 200 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
203. A method according to Claim 200 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
204. A method according to Claim 194 wherein said lipid is selected from the group consisting of oligolamellar lipids and multilamellar lipids.
205. A method according to Claim 204 wherein said lipid comprises one monolayer.
206. A method according to Claim 205 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
207. A method according to Claim 205 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
208. A method according to Claim 205 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
209. A method according to Claim 204 wherein said lipid comprises one bilayer.
210. A method according to Claim 209 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
211. A method according to Claim 209 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
212. A method according to Claim 209 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
213. A method according to Claim 60 wherein said vesicles comprise lipid-coated bubbles.
214. A method according to Claim 213 wherein said vesicles are selected from the group consisting of unilamellar vesicles, oligolamellar vesicles and multilamellar vesicles.
215. A method according to Claim 214 wherein said lipids comprise a phospholipid.
216. A method according to Claim 214 wherein said vesicles comprise unilamellar vesicles.
217. A method according to Claim 216 wherein said vesicles comprise one monolayer.
218. A method according to Claim 216 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
219. A method according to Claim 216 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
220. A method according to Claim 216 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
221. A method according to Claim 216 wherein said vesicles comprise one bilayer.
222. A method according to Claim 221 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
223. A method according to Claim 221 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
224. A method according to Claim 221 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
225. A method according to Claim 214 wherein said vesicles are selected from the group consisting of oligolamellar vesicles and multilamellar vesicles.
226. A method according to Claim 225 wherein said vesicles comprise one monolayer.
227. A method according to Claim 226 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
228. A method according to Claim 226 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
229. A method according to Claim 226 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
230. A method according to Claim 225 wherein said vesicles comprise one bilayer.
231. A method according to Claim 230 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
232. A method according to Claim 230 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
233. A method according to Claim 230 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
234. A system according to Claim 171 wherein said vesicles comprise lipid vesicles.
235. A system according to Claim 234 wherein said vesicles comprise lipid-coated bubbles.
236. A system according to Claim 234 wherein said vesicles are selected from the group consisting of unilamellar vesicles, oligolamellar vesicles and multilamellar vesicles.
237. A system according to Claim 236 wherein said vesicles comprise unilamellar vesicles.
238. A system according to Claim 237 wherein said vesicles comprise one monolayer.
239. A system according to Claim 238 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
240. A system according to Claim 238 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
241. A method according to Claim 238 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
242. A system according to Claim 237 wherein said vesicles comprise one bilayer.
243. A system according to Claim 242 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
244. A system according to Claim 242 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
245. A system according to Claim 242 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
246. A system according to Claim 236 wherein said vesicles are selected from the group consisting of oligolamellar vesicles and multilamellar vesicles.
247. A system according to Claim 246 wherein said vesicles comprise one monolayer.
248. A system according to Claim 247 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
249. A system according to Claim 247 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
250. A system according to Claim 248 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
251. A system according to Claim 246 wherein said vesicles comprise one bilayer.
252. A system according to Claim 251 wherein said lipid is a phospholipid and said gas or gaseous precursor is sulfur hexafluoride.
253. A system according to Claim 251 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
254. A method according to Claim 251 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropropane.
255. A method according to Claim 174 wherein said lipid is a polymerized lipid.
256. A method according to Claim 174 wherein said vesicles further comprise polyethylene glycol.
257. A method according to Claim 213 wherein said lipid is a polymerized lipid.
258. A method according to Claim 213 wherein said vesicles further comprise polyethylene glycol.
259. A system according to Claim 234 wherein said lipid is a polymerized lipid.
260. A system according to Claim 234 wherein said vesicles further comprise polyethylene glycol.
261. A method according to Claim 16 wherein said polymer comprises a polysaccharide.
262. A method according to Claim 261 wherein said polysaccharide comprises galactose.
263. A method according to Claim 261 wherein said gas is nitrogen gas.
264. A method according to Claim 71 wherein said polymer comprises a polysaccharide.
265. A method according to Claim 264 wherein said polysaccharide comprises galactose.
266. A method according to Claim 264 wherein said gas is nitrogen gas.
267. A method according to Claim 130 wherein said polymer comprises a polysaccharide.
268. A method according to Claim 267 wherein said polysaccharide comprises galactose.
269. A method according to Claim 267 wherein said gas is nitrogen gas.
270. A method according to Claim 157 wherein said vesicles comprise polymers.
271. A method according to Claim 270 wherein said polymer comprises a polysaccharide.
272. A method according to Claim 271 wherein said polysaccharide comprises galactose.
273. A method according to Claim 271 wherein said gas is nitrogen gas.
274. A method according to Claim 159 wherein said vesicles comprise polymers.
275. A method according to Claim 274 wherein said polymer comprises a polysaccharide.
276. A method according to Claim 275 wherein said polysaccharide comprises galactose.
277. A method according to Claim 275 wherein said gas is nitrogen gas.
278. A method according to Claim 171 wherein said vesicles comprise polymers.
279. A method according to Claim 278 wherein said polymer comprises a polysaccharide.
280. A method according to Claim 279 wherein said polysaccharide comprises galactose.
281. A method according to Claim 279 wherein said gas is nitrogen gas.
282. A method according to Claim 17 wherein said polymer comprises an acrylate.
283. A method according to Claim 282 wherein said gas is air.
284. A method according to Claim 17 wherein said polymer comprises a methacrylate.
285. A method according to Claim 284 wherein said gas is air.
286. A method according to Claim 17 wherein said polymer comprises a cyanoacrylate.
287. A method according to Claim 286 wherein said gas is air.
288. A method according to Claim 72 wherein said polymer comprises an acrylate.
289. A method according to Claim 288 wherein said gas is air.
290. A method according to Claim 72 wherein said polymer comprises a methacrylate.
291. A method according to Claim 290 wherein said gas is air.
292. A method according to Claim 72 wherein said polymer comprises a cyanoacrylate.
293. A method according to Claim 292 wherein said gas is air.
294. A method according to Claim 131 wherein said polymer comprises an acrylate.
295. A method according to Claim 294 wherein said gas is air.
296. A method according to Claim 131 wherein said polymer comprises a methacrylate.
297. A method according to Claim 296 wherein said gas is air.
298. A method according to Claim 131 wherein said polymer comprises a cyanoacrylate.
299. A method according to Claim 298 wherein said gas is air.
300. A method according to Claim 270 wherein said polymer comprises an acrylate.
301. A method according to Claim 300 wherein said gas is air.
302. A method according to Claim 270 wherein said polymer comprises a methacrylate.
303. A method according to Claim 302 wherein said gas is air.
304. A method according to Claim 270 wherein said polymer comprises a cyanoacrylate.
305. A method according to Claim 304 wherein said gas is air.
306. A method according to Claim 274 wherein said polymer comprises an acrylate.
307. A method according to Claim 306 wherein said gas is air.
308. A method according to Claim 274 wherein said polymer comprises a methacrylate.
309. A method according to Claim 308 wherein said gas is air.
310. A method according to Claim 274 wherein said polymer comprises a cyanoacrylate.
311. A method according to Claim 310 wherein said gas is air.
312. A method according to Claim 278 wherein said polymer comprises an acrylate.
313. A method according to Claim 312 wherein said gas is air.
314. A method according to Claim 278 wherein said polymer comprises a methacrylate.
315. A method according to Claim 314 wherein said gas is air.
316. A method according to Claim 278 wherein said polymer comprises a cyanoacrylate.
317. A method according to Claim 316 wherein said gas is air.
318. A method according to Claim 174 wherein said lipid is a phospholipid.
319. A method according to Claim 177 wherein said lipid is a phospholipid.
320. A method according to Claim 181 wherein said lipid is a phospholipid.
321. A method according to Claim 186 wherein said lipid is a phospholipid.
322. A method according to Claim 190 wherein said lipid is a phospholipid.
323. A method according to Claim 196 wherein said lipid is aphospholipid.
324. A method according to Claim 200 wherein said lipid is a phospholipid.
325. A method according to Claim 205 wherein said lipid is a phospholipid.
326. A method according to Claim 209 wherein said lipid is a phospholipid.
327. A method according to Claim 217 wherein said lipid is a phospholipid.
328. A method according to Claim 221 wherein said lipid is a phospholipid.
329. A method according to Claim 226 wherein said lipid is a phospholipid.
330. A method according to Claim 230 wherein said lipid is a phospholipid.
331. A system according to Claim 235 wherein said lipid is a phospholipid.
332. A system according to Claim 238 wherein said lipid is a phospholipid.
333. A system according to Claim 242 wherein said lipid is a phospholipid.
334. A system according to Claim 247 wherein said lipid is a phospholipid.
335. A system according to Claim 251 wherein said lipid is a phospholipid.
336. A method according to Claim 1 wherein said composition is reconstituted from a lyophilized composition.
337. A method according to Claim 2 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
338. A method according to Claim 337 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
339. A method according to Claim 337 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
340. A method according to Claim 14 wherein said gas or gaseous precursor comprises a perfluorocarbon.
341. A method according to Claim 340 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
342. A method according to Claim 341 wherein said perfluorocarbon is perfluoropropane.
343. A method according to Claim 45 wherein said composition is reconstituted from a lyophilized composition.
344. A method according to Claim 45 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
345. A method according to Claim 344 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
346. A method according to Claim 344 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
347. A method according to Claim 60 wherein said composition is reconstituted from a lyophilized composition.
348. A method according to Claim 61 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
349. A method according to Claim 348 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
350. A method according to Claim 348 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
351. A method according to Claim 69 wherein said gas or gaseous precursor comprises a perfluorocarbon.
352. A method according to Claim 351 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
353. A method according to Claim 352 wherein said perfluorocarbon is perfluoroplopane.
354. A method according to Claim 95 wherein said composition is reconstituted from a lyophilized composition.
355. A method according to Claim 95 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
356. A method according to Claim 355 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
357. A method according to Claim 355 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
358. A method according to Claim 115 wherein said composition is reconstituted from a lyophilized composition.
359. A method according to Claim 116 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
360. A method according to Claim 359 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
361. A method according to Claim 359 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
362. A method according to Claim 128 wherein said gas or gaseous precursor comprises a perfluorocarbon.
363. A method according to Claim 362 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
364. A method according to claim 363 wherein said perfluorocarbon is perfluoropropane.
365. A method according to Claim 157 wherein said composition is reconstituted from a lyophilized composition.
366. A method according to Claim 157 wherein said vesicles comprise lipids and wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
367. A method according to Claim 366 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
368. A method according to Claim 366 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
369. A method according to Claim 157 wherein said vesicles comprise proteins, and wherein said gas or gaseous precursor comprises a perfluorocarbon.
370. A method according to Claim 369 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
371. A method according to Claim 370 wherein said perfluorocarbon is perfluoropropane.
372. A method according to Claim 158 wherein said composition is reconstituted from a lyophilized composition.
373. A method according to Claim 158 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
374. A method according to Claim 373 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
375. A method according to Claim 373 wherein said gas or gaseous precursor is a combination of nitrogen and perfluolopropane.
376. A method according to Claim 159 wherein said composition is reconstituted from a lyophilized composition.
377. A method according to Claim 159 wherein said vesicles comprise lipids and wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
378. A method according to Claim 377 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
379. A method according to Claim 377 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
380. A method according to Claim 159 wherein said vesicles comprise proteins and wherein said gas or gaseous precursor comprises a perfluorocarbon.
381. A method according to Claim 380 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
382. A method according to claim 381 wherein said perfluorocarbon is perfluoropropane.
383. A method according to Claim 160 wherein said composition is reconstituted from a lyophilized composition.
384. A method according to Claim 160 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
385. A method according to Claim 384 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
386. A method according to Claim 384 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
387. A system according to Claim 171 wherein said composition is reconstituted from a lyophilized composition.
388. A system according to Claim 171 wherein said vesicles comprise lipids and wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
389. A system according to Claim 388 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
390. A system according to Claim 388 wherein said gas orgaseous precursor is a combination of nitrogen and perfluoropropane.
391. A system according to Claim 171 wherein said vesicles comprise proteins and wherein said gas or gaseous precursor comprises a perfluorocarbon.
392. A system according to Claim 391 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
393. A system according to Claim 392 wherein said perfluorocarbon is perfluoropropane.
394. A system according to Claim 172 wherein said composition is reconstituted from a lyophilized composition.
395. A system according to Claim 172 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
396. A system according to Claim 395 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
397. A system according to Claim 395 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
398. A method for providing an image of an intemal region of a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said vesicle composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in the image.
399. A method for providing an image of an intemal region of a patient comprising (i) administering to the patient a composition comprising, in an aqueous carrier, a surfactant and a gas or gaseous precursor, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in the image.
400. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
401. A method for providing an image of an internal region of a patient comprising (i) administering to the patient a composition comprising, in an aqueous carrier, a surfactant and a gas or gaseous precursor, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of the region, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
402. A method according to Claim 110 wherein said contrast agent comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants.
403. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said vesicle composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in said image.
404. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a composition comprising, in an aqueous carrier, a surfactant and a gas or gaseous precursor, and (ii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said composition is administered to the patient at a rate which substantially eliminates diagnostic artifacts in said image.
405. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
406. A method for diagnosing the presence of diseased tissue in a patient comprising (i) administering to the patient à composition comprising, in an aqueous carrier, a surfactant and a gas or gaseous precursor, (ii) flushing said composition, and (iii) scanning the patient using diagnostic imaging to obtain a visible image of any diseased tissue in the patient, wherein said composition is flushed at a rate which substantially eliminates diagnostic artifacts in the image.
407. A system according to Claim 161 wherein said contrast agent comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising surfactants.
408. A method according to Claim 398 wherein said composition is reconstituted from a lyophilized composition.
409. A method according to Claim 398 wherein said gas or gaseous precursor is selected from the group consisting of nitrogen, sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
410. A method according to Claim 409 wherein said gas or gaseous precursor is a combination of nitrogen and perfluorohexane.
411. A method according to Claim 409 wherein said gas or gaseous precursor is a combination of nitrogen and perfluoropropane.
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