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Abstract

The present invention pertains to proteinaceous gas- or gas precursor-containing microbubble contrast agents for use in ultrasound and/or MR imaging, in which the protein matrix is crosslinked by reaction with a bifunctional aldehyde (e.g., a dialdehyde such as glutaraldehyde or an .alpha.,.beta.-unsaturated aldehyde such as acrolein) in an aqueous medium at substantially neutral pH. The contrast agents exhibit improved in vivo and storage stabilities, particularly if the matrix is also reacted with a Schiff's base reducing agent such as a borohydride. Modification of the size distribution of such crosslinked proteinaceous gas-containing contrast agents, e.g. to reduce the mean size of the microbubbles, further enhances their stability and permits preparation of novel contrast agents having a particularly narrow microbubble size distribution.

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First Claim