US6231834B1
Expired / Lapsed
US
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Methods for ultrasound imaging involving the use of a contrast agent and multiple images and processing of same
Assignee: ImaRx Therapeutics Inc
•
Filing: 1997-12-02
•
Granted: 2001-05-15
•
Expires: 2017-12-02
Abstract
Abstract Improved methods for providing an image of an internal region of a patient. Embodiments of the invention involve the administration to the patient of a contrast agent which comprises, in an aqueous carrier, a lipid, protein, polymer or surfactant, and a gas. The patient is scanned using ultrasound imaging to obtain a visible image of the region. In embodiments of the invention, the scanning step may comprise applying a first quantity of ultrasound energy to the patient to provide a first image, followed by the application substantially immediately thereafter of a second quantity of ultrasound energy to provide a second image. The first and second images are then processed. The methods are particularly useful for obtaining on-line images of the cardiovascular region which may be employed, for example, to diagnose the presence of diseased tissue in the cardiovascular region of a patient.
Inventors
- 👤 Evan C. Unger
- 👤 Thomas A. Fritz
- 👤 Edward W. Gertz
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 09:57
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K49/227; A61K49/228
Claims Analysis
Total Claims: 117
Claim 1
Independent Claim
116 words
A method for providing an image of an internal region of a patient comprising (a) administering to the patient a contrast agent which comprises, in an aqueous carrier, a lipid, protein or polymer, and a gas, and (b) scanning the patient using ultrasound imaging to obtain a visible image of the region, wherein said scanning step comprises: (i) applying a first quantity of ultrasound energy to the patient to provide a first image; (ii) applying within about 100 milliseconds thereafter a second quantity of ultrasound energy to the patient to provide a second image; and (iii) processing said first and second images, wherein said processing step (iii) comprises subtracting said second image from said first image.
Claim 2
Independent Claim
116 words
A method for providing an image of an internal region of a patient comprising (a) administering to the patient a contrast agent which comprises, in an aqueous carrier, a lipid, protein or polymer, and a gas, and (b) scanning the patient using ultrasound imaging to obtain a visible image of the region, wherein said scanning step comprises: (i) applying a first quantity of ultrasound energy to the patient to provide a first image; (ii) applying within about 100 milliseconds thereafter a second quantity of ultrasound energy to the patient to provide a second image; and (iii) processing said first and second images, wherein said processing step (iii) comprises subtracting said second image from said first image.
Claim 3
Dependent Claim
13 words
A method according to claim 1 wherein said contrast agent comprises a lipid.
Claim 4
Dependent Claim
12 words
A method according to claim 2 wherein said lipid comprises a phospholipid.
Claim 5
Dependent Claim
21 words
A method according to claim 3 wherein said phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid.
Claim 6
Dependent Claim
21 words
A method according to claim 4 wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine.
Claim 7
Dependent Claim
11 words
A method according to claim 5 wherein said phosphatidylcholine comprises dipalmitoylphosphatidylcholine.
Claim 8
Dependent Claim
21 words
A method according to claim 6 wherein said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dioleoylphosphatidylethanolamine, N-succinyldioleoylphosphatidylethanolamine and 1-hexadecyl-2-palmitoylglycerophosphoethanolamine.
Claim 9
Dependent Claim
11 words
A method according to claim 7 wherein said phosphatidylethanolamine comprises dipalmitoylphosphatidylethanolamine.
Claim 10
Dependent Claim
13 words
A method according to claim 4 wherein said phosphatidic acid comprises dipalmitoylphosphatidic acid.
Claim 11
Dependent Claim
13 words
A method according to claim 2 wherein said lipid further comprises a polymer.
Claim 12
Dependent Claim
13 words
A method according to claim 10 wherein said polymer comprises a hydrophilic polymer.
Claim 13
Dependent Claim
12 words
A method according to claim 11 wherein said polymer comprises polyethylene glycol.
Claim 14
Dependent Claim
13 words
A method according to claim 1 wherein said contrast agent comprises a protein.
Claim 15
Dependent Claim
11 words
A method according to claim 13 wherein said protein comprises albumin.
Claim 16
Dependent Claim
13 words
A method according to claim 1 wherein said contrast agent comprises a polymer.
Claim 17
Dependent Claim
83 words
A method according to claim 15 wherein said polymer comprises 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, propylene 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.
Claim 18
Dependent Claim
44 words
A method according to claim 15 wherein said polymer comprises synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(ε-caprolactone), epoxy resin, poly(ethylene oxide), poly(propylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate and polystyrene-polyacrylonitrile.
Claim 19
Dependent Claim
12 words
A method according to claim 17 wherein said polymer comprises polyvinylidene-polyacrylonitrile copolymer.
Claim 20
Dependent Claim
13 words
A method according to claim 1 wherein said gas comprises a fluorinated gas.
Claim 21
Dependent Claim
23 words
A method according to claim 19 wherein said fluorinated gas is selected from the group consisting of a perfluorocarbon, sulfur hexafluoride and heptafluoropropane.
Claim 22
Dependent Claim
13 words
A method according to claim 20 wherein said fluorinated gas comprises a perfluorocarbon.
Claim 23
Dependent Claim
23 words
A method according to claim 21 wherein said perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluorocyclobutane.
Claim 24
Dependent Claim
19 words
A method according to claim 1 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 25
Dependent Claim
20 words
A method according to claim 23 wherein said gaseous precursor has a boiling point of greater than about 37° C.
Claim 26
Dependent Claim
14 words
A method according to claim 23 wherein said gaseous precursor comprises a fluorinated compound.
Claim 27
Dependent Claim
13 words
A method according to claim 25 wherein said fluorinated compound comprises a perfluorocarbon.
Claim 28
Dependent Claim
19 words
A method according to claim 26 wherein said perfluorocarbon is selected from the group consisting of perfluoropentane and perfluorohexane.
Claim 29
Dependent Claim
12 words
A method according to claim 1 wherein said contrast agent comprises vesicles.
Claim 30
Dependent Claim
19 words
A method according to claim 28 wherein said vesicles are selected from the group consisting of micelles and liposomes.
Claim 31
Dependent Claim
23 words
A method according to claim 2 wherein said lipid is selected from the group consisting of unilamellar lipids, oligolamellar lipids and multilamellar lipids.
Claim 32
Dependent Claim
12 words
A method according to claim 30 wherein said lipids comprise unilamellar lipids.
Claim 33
Dependent Claim
12 words
A method according to claim 31 wherein said lipid comprises one monolayer.
Claim 34
Dependent Claim
18 words
A method according to claim 32 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 35
Dependent Claim
17 words
A method according to claim 32 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 36
Dependent Claim
17 words
A method according to claim 32 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 37
Dependent Claim
19 words
A method according to claim 32 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 38
Dependent Claim
20 words
A method according to claim 36 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
Claim 39
Dependent Claim
12 words
A method according to claim 31 wherein said lipid comprises one bilayer.
Claim 40
Dependent Claim
18 words
A method according to claim 38 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 41
Dependent Claim
17 words
A method according to claim 38 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 42
Dependent Claim
17 words
A method according to claim 38 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 43
Dependent Claim
19 words
A method according to claim 38 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 44
Dependent Claim
18 words
A method according to claim 42 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
Claim 45
Dependent Claim
21 words
A method according to claim 30 wherein said lipids are selected from the group consisting of oligolamellar lipids and multilamellar lipids.
Claim 46
Dependent Claim
12 words
A method according to claim 44 wherein said lipids comprise one monolayer.
Claim 47
Dependent Claim
18 words
A method according to claim 45 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 48
Dependent Claim
17 words
A method according to claim 45 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 49
Dependent Claim
17 words
A method according to claim 45 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 50
Dependent Claim
19 words
A method according to claim 45 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 51
Dependent Claim
18 words
A method according to claim 49 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
Claim 52
Dependent Claim
12 words
A method according to claim 44 wherein said lipids comprise one bilayer.
Claim 53
Dependent Claim
18 words
A method according to claim 51 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 54
Dependent Claim
17 words
A method according to claim 51 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 55
Dependent Claim
17 words
A method according to claim 51 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 56
Dependent Claim
19 words
A method according to claim 51 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 57
Dependent Claim
18 words
A method according to claim 55 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
Claim 58
Dependent Claim
13 words
A method according to claim 2 wherein said lipid is a polymerized lipid.
Claim 59
Dependent Claim
13 words
A method according to claim 2 wherein said contrast agent further comprises polyethyleneglycol.
Claim 60
Dependent Claim
12 words
A method according to claim 28 wherein said vesicles comprise lipid vesicles.
Claim 61
Dependent Claim
23 words
A method according to claim 59 wherein said vesicles are selected from the group consisting of unilamellar vesicles, oligolamellar vesicles and multilamellar vesicles.
Claim 62
Dependent Claim
12 words
A method according to claim 60 wherein said vesicles comprise unilamellar vesicles.
Claim 63
Dependent Claim
12 words
A method according to claim 61 wherein said vesicles comprise one monolayer.
Claim 64
Dependent Claim
18 words
A method according to claim 62 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 65
Dependent Claim
17 words
A method according to claim 62 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 66
Dependent Claim
17 words
A method according to claim 63 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 67
Dependent Claim
19 words
A method according to claim 62 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 68
Dependent Claim
20 words
A method according to claim 66 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
Claim 69
Dependent Claim
13 words
A method according to claim 62 wherein said lipid is a polymerized lipid.
Claim 70
Dependent Claim
12 words
A method according to claim 61 wherein said vesicles comprise a bilayer.
Claim 71
Dependent Claim
18 words
A method according to claim 69 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 72
Dependent Claim
17 words
A method according to claim 69 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 73
Dependent Claim
17 words
A method according to claim 69 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 74
Dependent Claim
19 words
A method according to claim 69 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 75
Dependent Claim
18 words
A method according to claim 73 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
Claim 76
Dependent Claim
13 words
A method according to claim 69 wherein said lipid comprises a polymerized lipid.
Claim 77
Dependent Claim
21 words
A method according to claim 60 wherein said vesicles are selected from the group consisting of oligolamellar vesicles and multilamellar vesicles.
Claim 78
Dependent Claim
12 words
A method according to claim 76 wherein said vesicles comprise one monolayer.
Claim 79
Dependent Claim
18 words
A method according to claim 77 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 80
Dependent Claim
17 words
A method according to claim 77 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 81
Dependent Claim
17 words
A method according to claim 77 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 82
Dependent Claim
19 words
A method according to claim 77 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 83
Dependent Claim
18 words
A method according to claim 81 wherein said lipid is a phospholipid and said gaseous precursor is perfluoropentane.
Claim 84
Dependent Claim
13 words
A method according to claim 77 wherein said lipid is a polymerized lipid.
Claim 85
Dependent Claim
12 words
A method according to claim 76 wherein said vesicles comprise a bilayer.
Claim 86
Dependent Claim
18 words
A method according to claim 84 wherein said lipid is a phospholipid and said gas is sulfur hexafluoride.
Claim 87
Dependent Claim
17 words
A method according to claim 84 wherein said lipid is a phospholipid and said gas is perfluoropropane.
Claim 88
Dependent Claim
17 words
A method according to claim 84 wherein said lipid is a phospholipid and said gas is perfluorobutane.
Claim 89
Dependent Claim
19 words
A method according to claim 84 wherein said gas is derived, at least in part, from a gaseous precursor.
Claim 90
Dependent Claim
20 words
A method according to claim 88 wherein said lipid is a phospholipid and said gas or gaseous precursor is perfluoropentane.
Claim 91
Dependent Claim
12 words
A method according to claim 13 wherein said gas comprises a perfluorocarbon.
Claim 92
Dependent Claim
27 words
A method according to claim 90 wherein said perfluorocarbon is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane and perfluorononane.
Claim 93
Dependent Claim
11 words
A method according to claim 91 wherein said perfluorocarbon is perfluoropropane.
Claim 94
Dependent Claim
11 words
A method according to claim 13 wherein said protein is crosslinked.
Claim 95
Dependent Claim
11 words
A method according to claim 91 wherein said protein is crosslinked.
Claim 96
Dependent Claim
13 words
A method according to claim 1 wherein said region comprises the myocardial region.
Claim 97
Dependent Claim
13 words
A method according to claim 95 wherein said region comprises the left atrium.
Claim 98
Dependent Claim
26 words
A method according to claim 1 wherein said contrast agent is administered to the patient at a rate which substantially eliminates diagnostic artifacts in the image.
Claim 99
Dependent Claim
23 words
A method according to claim 1 wherein each of said first and second quantities of ultrasound energy comprises a pulse of ultrasound energy.
Claim 100
Dependent Claim
19 words
A method according to claim 98 wherein said first and second images are obtained during the same cardiac cycle.
Claim 101
Dependent Claim
21 words
A method according to claim 99 wherein said first pulse of ultrasound energy is applied at end systole or end diastole.
Claim 102
Dependent Claim
18 words
A method according to claim 100 wherein said first pulse of ultrasound energy is applied at end systole.
Claim 103
Dependent Claim
18 words
A method according to claim 100 wherein said first pulse of ultrasound energy is applied at end diastole.
Claim 104
Dependent Claim
24 words
A method according to claim 99 wherein said second pulse of ultrasound energy is applied from about 5 to less than about 100 milliseconds.
Claim 105
Dependent Claim
32 words
A method according to claim 103 wherein said second pulse of ultrasound energy is applied from about 10 to about 80 milliseconds after said application of said first pulse of ultrasound energy.
Claim 106
Dependent Claim
32 words
A method according to claim 104 wherein said second pulse of ultrasound energy is applied from about 20 to about 60 milliseconds after said application of said first pulse of ultrasound energy.
Claim 107
Dependent Claim
32 words
A method according to claim 105 wherein said second pulse of ultrasound energy is applied from about 30 to about 40 milliseconds after said application of said first pulse of ultrasound energy.
Claim 108
Dependent Claim
28 words
A method according to claim 106 wherein said second pulse of ultrasound energy is applied about 40 milliseconds after said application of said first pulse of ultrasound energy.
Claim 109
Dependent Claim
30 words
A method according to claim 99 wherein said first quantity of energy is applied at a time which corresponds to about the end of the T-wave in the patient's ECG.
Claim 110
Dependent Claim
30 words
A method according to claim 99 wherein said first quantity of energy is applied at a time which corresponds to about the end of the R-wave in the patient's ECG.
Claim 111
Dependent Claim
18 words
A method according to claim 1 wherein said processed images are displayed in gray scale or color format.
Claim 112
Dependent Claim
21 words
A method according to claim 1 which comprises administering said contrast agent to the patient at a rate of constant infusion.
Claim 113
Dependent Claim
16 words
A method according to claim 111 comprising administering said contrast agent using a constant infusion device.
Claim 114
Dependent Claim
13 words
A method according to claim 1 wherein said region comprises the myocardial region.
Claim 115
Dependent Claim
13 words
A method according to claim 113 wherein said region comprises the left atrium.
Claim 116
Independent Claim
119 words
A method for diagnosing the presence of diseased tissue in a patient comprising (a) administering to the patient a contrast agent which comprises, in an aqueous carrier, a lipid, protein or polymer, and a gas, and (b) scanning the patient using ultrasound imaging to obtain a visible image of any diseased tissue in the patient, wherein said scanning step comprises: (i) applying a first quantity of ultrasound energy to the patient to provide a first image; (ii) applying within about 100 milliseconds thereafter a second quantity of ultrasound energy to the patient to provide a second image; and (iii) processing said first and second images, wherein said processing step (iii) comprises subtracting said second image from said first image.
Claim 117
Independent Claim
119 words
A method for diagnosing the presence of diseased tissue in a patient comprising (a) administering to the patient a contrast agent which comprises, in an aqueous carrier, a lipid, protein or polymer, and a gas, and (b) scanning the patient using ultrasound imaging to obtain a visible image of any diseased tissue in the patient, wherein said scanning step comprises: (i) applying a first quantity of ultrasound energy to the patient to provide a first image; (ii) applying within about 100 milliseconds thereafter a second quantity of ultrasound energy to the patient to provide a second image; and (iii) processing said first and second images, wherein said processing step (iii) comprises subtracting said second image from said first image.
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