Contrast agents for ultrasonic imaging

• US 4,718,433 A
• Filed: 12/05/1985
• Issued: 01/12/1988
• Est. Priority Date: 01/27/1983
• Status: Expired due to Term

• Current Assignee: SLF Limited Partnership
• Original Assignee: Steven B. Feinstein
• Inventors: Feinstein, Steven B.
• Primary Examiner(s): Jaworski, Francis J.
• Application Number:
  US06/805,975
• Time in Patent Office: 768 Days
• Field of Search: 128/660-663, 424/2, 424/9, 530/427, 523/300
• US Class Current: 424/9.52
• CPC Class Codes: A61B 2090/3925 ultrasonic
• 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
• CPC Class Codes: G01S 15/899 Combination of imaging systems with ancillary equipment

Abstract

A method of ultrasonic imaging for use in medical procedures is disclosed. The method comprises providing specifically defined microbubbles formed by sonicating a bicompatible liquid comprising a sonicated aqueous protein solution, preferably a 5% solution of human serum albumin, and denaturing the protein therein by heat or chemical methods; injecting the microbubbles into an animal or human to thereby alter the acoustic properties of an area to be imaged; and then ultrasonically scanning the area so as to obtain an ultrasound scanning image.

Claims

1. The method of ultrasonic imaging in which microbubbles are injected into a mammal to alter the accoustic properties of a predetermined area which is then ultrasonically scanned to obtain an image of the area for use in medical procedures, wherein the improvement comprises the steps of forming an aqueous protein solution, subjecting said solution to high frequency sonication while heating the solution sufficiently to denature portions of the protein, said sonication forming microbubbles of relatively uniform size stabilized by the denatured protein, and using the stabilized microbubbles as an injectate for said ultrasonic imaging.

2. The method of claim 1 in which the improvement further comprises forming said aqueous protein solution from albumin.

3. The method of claim 1 in which the improvement further comprises forming said stabilized microbubbles with substantially all of the microbubbles having diameters less than 9 microns.

4. The method of claim 1 in which the improvement further comprises forming said stabilized microbubbles with the microbubbles having diameters predominantly in the range from 2 to 5 microns.

5. The method of claims 1, 3, or 4 in which said stabilized microbubbles are used by injection into a peripheral vein for ultrasonic heart imaging via transpulmonary passage.

6. The method of ultrasonic imaging in which microbubbles are injected into a mammal to alter the accoustic properties of a predetermined area which is then ultrasonically scanned to obtain an image of the area for use in medical procedures, wherein the improvement comprises the steps of forming an aqueous protein solution, subjecting said solution to high frequency sonication while heating the solution sufficiently by means of the sonication to denature portions of the protein, said sonication forming microbubbles stabilized by the denatured protein with substantially all of the microbubbles having diameters less than 9 microns, and using the stabilized microbubbles as an injectate for said ultrasonic imaging.

7. The method of claim 6 in which the improvement further comprises forming said protein solution from human serum albumin.

8. The method of claims 6 or 7 in which the improvement further comprises forming said stabilized microbubbles with the microbubbles having diameters predominantly in the range from 2 to 5 microns.

9. The method of claims 6 or 7 in which said stabilized microbubbles are used by injection into a peripheral vein for ultrasonic heart imaging via transpulmonary passage.