Ultrasonic contrast agents for color Doppler imaging

• US 5,425,366 A
• Filed: 06/07/1993
• Issued: 06/20/1995
• Est. Priority Date: 02/05/1988
• Status: Expired due to Term

• Current Assignee: Acusphere Incorporated
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Heldmann, Dieter, Reinhardt, Michael, Fritzsch, Thomas, Siegert, Joachim
• Primary Examiner(s): Jaworski, Francis
• Application Number:
  US08/072,748
• Time in Patent Office: 743 Days
• Field of Search: 128/660.02, 128/662.02, 424/9, 424/11
• US Class Current: 600/458
• CPC Class Codes: A61K 49/226 Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
• CPC Class Codes: A61K 49/228 Host-guest complexes, clathrates, chelates
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01S 15/8979 Combined Doppler and pulse-echo imaging systems

Abstract

The invention relates to a method for obtaining an ultrasonic image of a patient with ultrasonic color Doppler modality with microparticulate ultrasonic contrast agents in regions where the ultrasonic contrast agents are essentially motionless.

Claims

1. A method of obtaining an ultrasonic image of a patient comprising administering to the patient microparticles comprising a cavity containing a gas or a volatile fluid, which particles upon exposure to an effective color Doppler sonography modality produce a Doppler signal when the particles are essentially motionless in the patient, and imaging said patient with an effective ultrasonic color Doppler modality in a region where said microparticles are essentially motionless.

2. A method of claim 1, comprising administering microparticles which comprise a polymeric material having entrapped therein gases and/or fluids having a boiling point below 60°

C. in free or bonded form and/or microbubbles comprising a gelatin or albumin microcapsule having a gas or volatile fluid entrapped therein.

3. A method of claim 2, comprising administering microparticles which are gas-filled gelatin microcapsules.

4. A method of claim 2, comprising administering microparticles which are gas-filled microcapsules having walls comprising denatured protein.

5. A method of claim 4, wherein the denatured protein is denatured albumin or human serum albumin.

6. A method of claim 1, comprising administering microparticles which are gas- or liquid-filled microcapsules having walls of a biodegradable polyester of a gas- or liquid-filled polycyanoacrylate or a biodegradable polyester of an α

-, β

- or γ

-hydroxycarboxylic acid.

7. A method of claim 1, comprising administering microparticles which are gas- or liquid-filled microcapsules having walls of a biodegradable polyaldehyde which optionally contains additives and/or crosslinks capable of copolymerization, surfactants or surfactant mixtures, coupling agents or biomolecules or macromolecules optionally bound by these coupling agents.

8. A method of claim 1, wherein the region where said microparticles are essentially motionless is in the reticuloendothelial system.

9. A method as in claim 1, wherein the region where said microparticles are essentially motionless is in the myocardium.

10. A method as in claim 1, wherein the region where said microparticles are essentially motionless is in the GI tract.

11. A method as in claim 1, wherein the region where said microparticles are essentially motionless is in the lymphatic system, liver or spleen.

12. A method as in claim 1, comprising administering microparticles which are administered in an amount which provides 10⁵ -10⁷ microparticles per cm³ of the tissue to be imaged.

13. A method as in claim 1, comprising administering microparticles by peroral, intraarticular, intravesical, transvaginal, intraperitoneal or intravenous administration.

14. A method according to claim 1, comprising administering microparticles which contain a gas which is air, nitrogen, oxygen, carbon dioxide, hydrogen, ammonia, ethylene, methane, ethane, propane, butane or a mixture thereof.

15. A method according to claim 1, wherein the patient is imaged with effective ultrasonic radiation and the Doppler effects are photographically recorded as a change in color.

16. A method of obtaining an ultrasonic image of a patient comprising administering to the patient, microparticles comprising a cavity containing a volatile fluid which particles become sited in tissue or a body cavity of said patient and become essentially motionless therein, irradiating such tissue or cavity with an ultrasound frequency of a strength effective to burst said particles and imaging said patient by recording the ultrasound frequencies scattered as a result of said bursting.

17. A method of claim 16, comprising administering microparticles which are gas- or liquid-filled microcapsules having walls of a biodegradable polyester of a gas- or liquid-filled polycyanoacrylate or a biodegradable polyester of an α

-, β

- or γ

-hydroxycarboxylic acid.

18. A method of claim 16, comprising administering microparticles which are gas- or liquid-filled microcapsules having walls of a biodegradable polyaldehyde, which optionally contains additives and/or crosslinks capable of copolymerization, surfactants or surfactant mixtures, coupling agents or biomolecules or macromolecules optionally bound by these coupling agents.

19. A method of claim 16, wherein the region where said microparticles are essentially motionless is in the reticuloendothelial system, the myocardium or the GI tract.