Harmonic ultrasound imaging with microbubbles

• US 20030044355A1
• Filed: 10/09/2002
• Published: 03/06/2003
• Est. Priority Date: 09/28/1994
• Status: Active Grant

• Current Assignee: Targeson, Inc.
• Original Assignee: Photogen Technologies Inc.
• Inventors: Schutt, Ernest G.
• Granted Patent: US 7,374,744 B2
• Time in Patent Office: Days
• US Class Current: 424/9.52
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

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.

Claims

1. A method of ultrasound harmonic imaging using ultrasonic energy comprised of compression waves 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 containing at least one gas other than water vapor having a vapor pressure of over 23 mm Hg at 37°

C.;

less than about 1% wt./wt. solubility/miscibility in water;

a concentration in the gas phase when detected greater than 2% mole fraction, and a partial pressure when compressed by said compression wave equal to its vapor pressure at 37°

C. when compressed by said ultrasound wave; and

ultrasonically imaging at least a portion of said object or body and detecting at least one frequency other than the transmitted frequency.

2. The method of claim 1, wherein the at least one gas is selected from the group consisting of perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluorocyclopentane, 1,1,2-trichlorotrifluoroethane, sulfur hexafluoride, cyclopentane, methylene chloride, pentane and hexane or mixtures thereof.

3. A method of ultrasound 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 comprising at least one gas other than water vapor;

wherein said gas has a vapor pressure of over 23 mm Hg at 37°

C.;

less than about 1% wt./wt. solubility/miscibility in water at a temperature of about 23°

C. and a pressure of about 1 atmosphere;

a concentration in the gas phase when detected greater than 2% mole fraction, and a partial pressure when compressed by said compression wave equal to its vapor pressure at 37°

C. when compressed by said ultrasound wave; and

,

ultrasonically imaging at least a portion of said object or body and detecting a frequency other than the transmitted frequency.

4. The method of claim 3, wherein said at least one gas is a hydrocarbon or a fluorocarbon gas.

5. A method of ultrasound harmonic imaging comprising the following steps:

introducing into a body a contrast agent comprised of microbubbles;

ultrasonically imaging at least a portion of said body;

said microbubbles being designed to enhance the nonlinear response of the microbubble when irradiated by ultrasonic energy by utilizing a gas other than water vapor that at least partially liquefies under the peak pressure of the ultrasound wave; and

,

detecting a frequency other than the transmitted frequency.

6. The method of claim 5 wherein the microbubbles contain a fluorocarbon or a hydrocarbon gas.

7. The method of claim 5 wherein the microbubbles contain a mixture of gases.

8. The method of claim 5 wherein the microbubbles are stabilized by their gas or gas mixture.

9. A method of ultrasound harmonic imaging using ultrasonic energy transmitted by an ultrasonic source to an object or body to be imaged wherein an ultrasound contrast agent comprised of microbubbles with membranes are introduced into said object or body and said microbubbles are designed to produce enhanced harmonics, wheren:

said microbubbles contain at least one gas other than water which at least partially dissolves in the microbubble membrane when exposed to the peak pressure of the ultrasound wave; and

,

detecting a frequency other than the transmitted frequency.

10. The method of claim 9 wherein the microbubble membrane comprises a surfactant.

11. The method of claim 10 wherein the surfactant is non-Newtonian.

12. The method of claim 9 wherein said microbubbles are coated with a monolayer of surfactant.

13. A method of ultrasound 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 an ultrsound contrast agent comprising microbubbles comprising membranes wherein said microbubble membrances contain a surfactant wherein said surfactant increases surface tension as the bubble expands and decreases surface tension as the bubble contracts;

wherein said microbubbles contain a gaseous material;

ultrasonically imaging at least a portion of said object or body;

detecting a nonlinear signal.

14. The method of claim 13 wherein said gaseous material is either a hydrocarbon or fluorocarbon gas.

15. A method of ultrasound 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;

said 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 different from the resonant frequency of the microbubbles.

16. The method of claim 15 wherein the microbubbles contain a gaseous material that is either a hydrocarbon or a fluorocarbon gas.

17. A method of ultrasound harmonic imaging of an object or body comprising the following steps:

introducing into said object or body a contrast agent comprising microbubbles which radiate ultrasonic energy at a frequency which is different from that transmitted by the ultrasonic source and that is different from the resonant frequency of the microbubbles;

transmitting ultrasonic energy from an utlrasonic source to said object or body; and

,

detecting radiated energy from said object or body which is of a different frequency than the radiated energy transmitted from the ultrasonic source and the resonant frequency of the microbubbles.

18. The method of claim 17 wherein the microbubble is osmotically stabilized.

19. A method of ultrasound imaging comprising the following steps:

introducing into a body a contrast agent comprised of microbubbles;

ultrasonically imaging at least a portion of said body;

said microbubbles being designed to enhance the nonlinear response of the microbubble when irradiated by the ultrasonic energy by utilizing a gas other than water vapor that at least partially liquefies under the peal pressure of the ultrasound wave; and

,

detecting the enhanced nonlinear response of said microbubbles.

20. The method of claim 42 wherein said microbubbles comprise a gas selected from the group of perfluorohexane, perfluoropentane, perfluorocyclopentane, 1,1,2-trichlorotrifluoroethane, sulfur hexafluoride, cyclopentane, methylene chloride, pentane and hexane or mixtures thereof.

21. A method of ultrasound harmonic imaging using ultrasonic energy comprised of compression waves transmitted by an ultrasonic source to an object or body to be imaged, comprising:

introducing into said object or body a contrast agent containing at least one gas having a vapor pressure of over 23 mm Hg at 37 °

C.;

less than about 1 % wt./wt. solubility/miscibility in water;

a concentration in gas phase when detected greater than 2% mole fraction, and a partial pressure when compressed by said compression wave equal to its vapor pressure at 37 °

C. when compressed by said ultrasound wave; and

,

ultrasonically imaging at least a portion of said object or body and detecting the enhanced non-linear response.

22. The method of claim 21 wherein the at least one gas is a fluorocarbon gas.