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US5540909A Expired / Lapsed US ⏱️ 0.0 years remaining

Harmonic ultrasound imaging with microbubbles

Assignee: PHOTOGEN TECHNOLOGIES Inc
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Filing: 1994-09-28
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Granted: 1996-07-30
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Expires: 2014-09-28
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Abstract

Abstract A method for ultrasonic harmonic imaging is disclosed, which uses microbubbles particularly selected for their properties of reradiating ultrasound energy at frequencies other than the exciting frequency.

Inventors

  • 👤 Ernest G. Schutt

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 04:17
CPC Classifications
A; A61; A61B; A61B8/00; A61B8/48; A61B8/481; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223

Claims Analysis

Total Claims: 30
Claim 1
Independent Claim 93 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles having generally spherical membranes and containing gaseous material having vapor pressure at 37° C. over 23 mm Hg, less than about 1% wt./wt. solubility/miscibility in water, concentration in gas phase when detected greater than 2% mole fraction, and a concentration greater than 50% of its saturation concentration; and ultrasonically imaging at least a portion of said object or body.
Claim 2
Independent Claim 93 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles having generally spherical membranes and containing gaseous material having vapor pressure at 37° C. over 23 mm Hg, less than about 1% wt./wt. solubility/miscibility in water, concentration in gas phase when detected greater than 2% mole fraction, and a concentration greater than 50% of its saturation concentration; and ultrasonically imaging at least a portion of said object or body.
Claim 3
Dependent Claim 27 words
The method of claim 1, wherein said material is selected from the group consisting of perfluorohexane, perfluoropentane, perfluorocyclopentane, 1,1,2-trichlorotrifluoroethane, sulfur hexafluoride, cyclopentane, methylene chloride, pentane and hexane.
Claim 4
Dependent Claim 10 words
The method of claim 1, wherein said concentration is 25%.
Claim 5
Dependent Claim 10 words
The method of claim 1, wherein said concentration is 100%.
Claim 6
Dependent Claim 11 words
The method of claim 1, wherein said membranes comprise a surfactant.
Claim 7
Independent Claim 101 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles having generally spherical membranes and containing material that comprises at least 2% mole fraction of a gas that has a solubility of its liquid phase in hexane at 37° C. of more than about 10% mole/mole and a water solubility/miscibility of its liquid phase of less than about 1% wt./wt. in water at 37° C.; and ultrasonically imaging at least a portion of said object or body.
Claim 8
Independent Claim 101 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles having generally spherical membranes and containing material that comprises at least 2% mole fraction of a gas that has a solubility of its liquid phase in hexane at 37° C. of more than about 10% mole/mole and a water solubility/miscibility of its liquid phase of less than about 1% wt./wt. in water at 37° C.; and ultrasonically imaging at least a portion of said object or body.
Claim 9
Dependent Claim 14 words
The method of claim 6, wherein said gas is a hydrocarbon or a fluorocarbon.
Claim 10
Dependent Claim 37 words
The method of claim 6, wherein said gas is selected from the group consisting of perfluorohexane, perfluoropentane, perfluorocyclopentane, 1,1,2-trichlorotrifluoroethane, sulfur hexafluoride, cyclopentane, methylene chloride, pentane, hexane, dichlorodifluoromethane, trichloromonofluoromethane, perfluorobutane, perfluorocyclobutane, perfluoropropane, butane, cyclobutane, propane, methane, and ethane.
Claim 11
Dependent Claim 11 words
The method of claim 6, wherein said membranes comprise a surfactant.
Claim 12
Dependent Claim 10 words
The method of claim 9, wherein said surfactant is fluorinated.
Claim 13
Dependent Claim 18 words
The method of claim 6, wherein said material comprises at least about 25% mole fraction of said gas.
Claim 14
Dependent Claim 16 words
The method of claim 6, wherein said material comprises about 100% mole fraction of said gas.
Claim 15
Independent Claim 66 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles stabilized with at least one surfactant, said stabilized microbubbles generating harmonics with an efficiency greater than a free air bubble; and ultrasonically imaging at least a portion of said object or body.
Claim 16
Independent Claim 66 words
A method of ultrasonic harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged, comprising: introducing into said object or body a contrast agent comprising microbubbles stabilized with at least one surfactant, said stabilized microbubbles generating harmonics with an efficiency greater than a free air bubble; and ultrasonically imaging at least a portion of said object or body.
Claim 17
Dependent Claim 38 words
The method of claim 13, wherein said surfactant will change the surface tension of water by more than 5 dynes/cm when the area per molecule of surfactant has changed by 10% as measured on a Langmuir film balance.
Claim 18
Dependent Claim 18 words
The method of claim 13, wherein said surfactant has a component having a hydrophilic-lipophilic balance less than 11.
Claim 19
Dependent Claim 16 words
The method of claim 15, wherein said hydrophilic-lipophilic balance is less than or equal to 8.
Claim 20
Dependent Claim 31 words
The method of claim 13, wherein said surfactant has a component with a molecular weight over 1,000 and capable of lowering the surface tension of water to 40 dynes/cm or lower.
Claim 21
Dependent Claim 36 words
The method of claim 13, wherein said surfactant is capable of lowering the surface tension of water to 40 dynes/cm or lower and has a critical micelle concentration of 0.3 or less volume fraction in water.
Claim 22
Dependent Claim 10 words
The method of claim 13, wherein said surfactant is non-Newtonian.
Claim 23
Dependent Claim 96 words
In a method for ultrasonic harmonic imaging of an object or body comprising introducing into said object or body a contrast agent and transmitting ultrasonic energy from an ultrasonic source to said object or body and detecting radiated energy from said object or body, the improvement comprising: said contrast agent comprising microbubbles having the property of radiating imageable ultrasonic energy at a frequency which is different from that transmitted by the ultrasonic source and that is independent of the resonant frequency of the microbubbles; and said detecting step utilizing a different frequency than said transmitting step.
Claim 24
Dependent Claim 96 words
In a method for ultrasonic harmonic imaging of an object or body comprising introducing into said object or body a contrast agent and transmitting ultrasonic energy from an ultrasonic source to said object or body and detecting radiated energy from said object or body, the improvement comprising: said contrast agent comprising microbubbles having the property of radiating imageable ultrasonic energy at a frequency which is different from that transmitted by the ultrasonic source and that is independent of the resonant frequency of the microbubbles; and said detecting step utilizing a different frequency than said transmitting step.
Claim 25
Dependent Claim 14 words
The method of claim 20, wherein said microbubbles contain a gas or gas mixture.
Claim 26
Dependent Claim 17 words
The method of claim 21, wherein said microbubbles are stabilized by their gas or gas mixture contents.
Claim 27
Dependent Claim 55 words
The method of claim 20, wherein said microbubbles are produced by spray drying a liquid formulation containing a biocompatible membrane-forming material to form a microsphere powder therefrom; combining the microspheres with a gas osmotic agent; and mixing an aqueous phase with the powder, wherein said powder substantially dissolves in the aqueous phase to form microbubbles.
Claim 28
Dependent Claim 15 words
The method of claim 22, wherein said microbubbles are coated with a monolayer of surfactant.
Claim 29
Dependent Claim 32 words
In method for harmonic ultrasound imaging utilizing microbubbles, the improvement comprising: providing at least one hydrocarbon gas or fluorocarbon gas in said microbubbles in a concentration of at least 2% mole fraction.
Claim 30
Dependent Claim 32 words
In method for harmonic ultrasound imaging utilizing microbubbles, the improvement comprising: providing at least one hydrocarbon gas or fluorocarbon gas in said microbubbles in a concentration of at least 2% mole fraction.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1999-07-30 2000-01-29 2000-07-30 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2003-07-30 2004-01-29 2004-07-30 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2007-07-30 2008-01-29 2008-07-30 $7700.00 Window Closed / Lapsed

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