Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and a second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ratio of from about 1:100 to about 1000:1, and wherein the first gas has a vapor pressure of at least about (760−x) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; kits for preparing microbubbles; and methods for using such microbubbles as ultrasound contrast agents.

Abstract: Ultrasonic visualization of a subject, particularly of perfusion in the myocardium and other tissues, is performed using novel gas-containing contrast agent preparations which promote controllable and temporary growth of the gas phase in vivo following administration and can therefore act as deposited perfusion tracers. The preparations include a coadministerable composition comprising a diffusible component capable of inward diffusion into the dispersed gas phase to promote temporary growth thereof. In cardiac perfusion imaging the preparations may advantageously be coadministered with vasodilator drugs such as adenosine in order to enhance the differences in return signal intensity from normal and hypoperfused myocardial tissue respectively.

Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and a second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ratio of from about 1:100 to about 1000:1, and wherein the first gas has a vapor pressure of at least about (760−x) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; kits for preparing microbubbles; and methods for using such microbubbles as ultrasound contrast agents.

Abstract: A gas emulsion forming composition comprising a dry, hollow, particulate, approximately microspherical material permeated with a gas or gas mixture, which upon dissolution in aqueous liquid forms a gas emulsion comprising a plurality of bubbles surrounded by a layer of at least a first and a second surfactant, wherein the first surfactant consists essentially of a phospholipid or mixture of phospholipids having at least one acyl chain which comprises at least 10 carbon atoms, and comprising at least about 5% w/w of total surfactant, and wherein the second surfactant may or may not be a phospholipid and is more water soluble than the first surfactant; kits for preparing such microbubbles; and methods for using such microbubbles as contrast agents.

Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ration of from about 1:100 to abut 1000:1, and wherein the first gas has a vapor pressure of at least about (760—X) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; methods and kits for preparing microbubbles; and methods for using such microbubbles as contrast agents.

Abstract: A local and site-specific drug delivery apparatus for delivering a drug to a specific site is characterized by the combination of a carrier material which reflects or absorbs or emits electromagnetic or mechanical (e.g. ultrasonic) vibrations enabling the monitoring of the material, a drug associated with the carrier material, and a local-delivery mechanism for delivering the carrier material and the drug to a specific site. The local-delivery mechanism may comprise a local-delivery catheter, such as a balloon-type catheter, and the drug delivery apparatus may additionally include a monitor for monitoring the delivery of the drug to the specific site, such as an ultrasonic imaging system. The drug delivery apparatus may also include a vibration generator for inducing release of the drug from the carrier material when the carrier material is at the specific site, such as a generator of ultrasonic energy.

Abstract: Microspheres are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microspheres and (ii) reducing the water-solubility of at least the outside of the intermediate microspheres. Suitable wall-forming materials include proteins such as albumin and gelatin. The microsphere have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilisation and cross-linking of the wall-forming material allows novel microsphere preparations to be produced. In particular, the microspheres may be 15-20 &mgr;m, targeted to selected areas of the body or of prolonged life in the circulation.

Abstract: Microspheres are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microspheres and (ii) reducing the water-solubility of at least the outside of the intermediate microspheres. Suitable wall-forming materials include proteins such as albumin and gelatin. The microsphere have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilisation and cross-linking of the wall-forming material allows novel microsphere preparations to be produced. In particular, the microspheres may be 15-20 &mgr;m, targeted to selected areas of the body or of prolonged life in the circulation.

Abstract: The invention relates to microcapsules to a microcapsule with a mean size from a fraction of micrometer to 1000 micrometers having a biodegradable membrane encapsulating a gas core. The membrane comprising one or more biodegradable water insoluble lipids or mixtures thereof and optionally mixtures of the lipids with up to 75% by weight of biodegradable polymers encapsulates the core which is filled with air or a gas. Microcapsules disclosed, may be non-coalescent, dry and instantly dispersible, when in suspension in a physiologically acceptable carrier are useful as delivery vehicles for therapeutically active agents and/or as contrast agents for echographic imaging of organs of human or animal body.

Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

Abstract: Methods for increasing the T1 of injectable microbubble formulations of hyperpolarized 3He include the step of introducing the hyperpolarized 3He to a quantity of microbubbles held in a chamber and increasing the pressure therein to facilitate the movement or loading of the 3He into the microbubbles. Subsequently, a limited quantity of carrier liquid or a carrier liquid solution alone, or pre-mixed with 3He, can be introduced to the microbubble/3He in the chamber to inhibit the tendency of the 3He to leach out of the bubble. Related pharmaceutical products and associated containers as well as an evacuation based method for rapid mixing and delivery of the bubbles and the 3He is also disclosed. An additional method for dissolving 129Xe gas by using bubbles as an accelerant is also described.

Abstract: Novel gas filled microspheres useful as magnetic resonance imaging (MRI) contrast agents are provided.

Abstract: The invention relates to gas-containing microparticles and nanoparticles that consist of biodegradable, synthetic polymers based on hydrophobized polysaccharides, agents that contain these particles for ultrasound diagnosis, and a process for the production of the particles and agents.

Abstract: Compositions containing microparticles having at least one surface-active substance and at least one non-surface-active solid with a gaseous component containing a halogenated hydrocarbon that is gaseous at body temperature, wherein the gaseous component is more poorly water-soluble than air. Also, ultrasonic contrast media containing such composition, processes for their production, kits for their production and methods of use.

Abstract: The present invention describes, among other things, the surprising discovery that gaseous precursor filled compositions are profoundly more effective as acoustically active contrast agents when they are thermally preactivated to temperatures at or above the boiling point of the instilled gaseous precursor prior to their in vivo administration to a patient. Further optimization of contrast enhancement is achieved by administering the gaseous precursor filled compositions to a patient as an infusion. Enhanced effectiveness is also achieved for ultrasound mediated targeting and drug delivery.

Abstract: Disclosed are injectable suspensions of gas filled microbubbles in an aqueous carrier liquid usable as contrast agents in ultrasonic echography. The suspensions comprise amphipathic compounds of which at least one may be a laminarized phospholipid as a stabiliser of the microbubbles against collapse with time and pressure. The concentration of phospholipids in the carrier liquid is below 0.01% wt but is at least equal to or above that at which phospholipid molecules are present solely at the gas microbubble-liquid interface. Also disclosed are methods of preparation of the stable suspensions of gas filled microbubbles, as well as dry formulations which, upon reconstitution in an aqueous carrier liquid, will form the injectable suspensions of gas filled microbubbles of the invention and methods of making and using the same The preferred dry formulations are stable when stored over time and at temperatures above ambient temperature and further comprise a lipid acid preserving agent additive.

Abstract: Gas filled microbubble and microballoon suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles and microballoons used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are disclosed that have advantageous properties. Dry formulations useful in making the contrast agents are also disclosed.

Abstract: Substantially homogeneous aqueous suspensions of low density microspheres are presented as contrast media for imaging the gastrointestinal tract and other body cavities using computed tomography. In one embodiment, the low density microspheres are gas-filled. With computed tomography, the contrast media serve to change the relative density of certain areas within the gastrointestinal tract and other body cavities, and improve the overall diagnostic efficacy of this imaging method.

Abstract: A method of assessing relative rates of blood flow in the coronary arteries which involves observing one or more flow parameters in respect of contrast agent-containing blood flowing in at least one coronary artery of a subject, by generating a sequence of ultrasound images of the heart in a plane at least substantially perpendicular to the cardiac axis. Ultrasound imaging techniques which may be employed include power Doppler imaging and second harmonic B-mode or power Doppler imaging.

Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and a second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ratio of from about 1:100 to about 1000:1, and wherein the first gas has a vapor pressure of at least about (760−x) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; methods and kits for preparing microbubbles; and methods for using such microbubbles as contrast agents.

Abstract: Oil-in-water emulsions in which the oil phase comprises condensed or dissolved oil-soluble gas/fluid or gas precursor are useful as ultrasound contrast agents. Such products contain insignificant amounts of free gas bubbles or microbubbles in their stored form and exhibit good stability, but may be designed to promote rapid microbubble generation immediately before or upon administration.

Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ration of from about 1:100 to abut 1000:1, and wherein the first gas has a vapor pressure of at least about (760−X) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; methods and kits for preparing microbubbles; and methods for using such microbubbles as contrast agents.

Abstract: A gas emulsion forming composition comprising a dry, hollow, particulate, approximately microspherical material permeated with a gas or gas mixture, which upon dissolution in aqueous liquid forms a gas emulsion comprising a plurality of bubbles surrounded by a layer of at least a first and a second surfactant, wherein the first surfactant consists essentially of a phospholipid or mixture of phospholipids having at least one acyl chain which comprises at least 10 carbon atoms, and comprising at least about 5% w/w of total surfactant, and wherein the second surfactant may or may not be a phospholipid and is more water soluble than the first surfactant; kits for preparing such microbubbles; and methods for using such microbubbles as contrast agents.

Abstract: Microparticulate contrast agents comprising gas or a gas precursor encapsulated by a non-polymeric and non-polymerisable wall-forming material are readily characterisable materials exhibiting surprising structural integrity and stability.

Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.

Abstract: Microbubble dispersions stabilized by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilized by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

Abstract: Methods for increasing the T1 of injectable microbubble formulations of hyperpolarized 3He include the step of introducing the hyperpolarized 3He to a quantity of microbubbles held in a chamber and increasing the pressure therein to facilitate the movement or loading of the 3He into the microbubbles. Subsequently, a limited quantity of carrier liquid or a carrier liquid solution alone, or pre-mixed with 3He, can be introduced to the microbubble/3He in the chamber to inhibit the tendency of the 3He to leach out of the bubble. Related pharmaceutical products and associated containers as well as an evacuation based method for rapid mixing and delivery of the bubbles and the 3He is also disclosed. An additional method for dissolving 129Xe gas by using bubbles as an accelerant is also described.

Abstract: A method of obtaining an image of a part of a patient, comprising: (a) providing microcapsules which have been formed by (i) providing a solution of a material in an aqueous solvent containing water and a liquid of greater volatility than water and (ii) spraying the said solution into a gas such that the aqueous solvent evaporates, thereby forming hollow microcapsules suitable for use as an echogenic contrast agent, (b) injecting the microcapsules into a patient, and (c) subjecting the patient to ultrasonic energy to obtain an image based on the ultrasound reflectivity transmissibility or resonance of the microcapsules, characterized in that at least 5 minutes elapse between steps (b) and (c). The patient can be exercised between administration and imaging without having to be reinjected.

Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.

Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.

Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.

Abstract: A microbubble preparation formed of a plurality of microbubbles comprising a first gas and a second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ratio of from about 1:100 to about 1000:1, and wherein the first gas has a vapor pressure of at least about (760−x) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; kits for preparing microbubbles; and methods for using such microbubbles as ultrasound contrast agents.

Abstract: Targeted ultrasound contrast agents are described. The contrast agents are porous particles of an inorganic material containing an entrapped gas or liquid and having an average particle diameter of about 0.05 to 500 microns. The outer surfaces of the particles incorporate a targeting ligand to target delivery of the contrast agent.

Abstract: The present invention describes processes for the preparation of a lipid blend and a uniform filterable phospholipid suspension containing the lipid blend, such suspension being useful as an ultrasound contrast agent.

Abstract: The invention discloses an ultrasound contrast media comprising a microbubble shell and a composition of the general formula: A-P-L, wherein A is an ultrasound contrast agent microbubble-shell binding moiety; P is a spacer arm; and L is a ligand. The present invention discloses compositions, methods of imaging, and methods for attachment of targeting ligands to USCM agents, allowing selective targeting of USCM agents to desired sites.

Abstract: Agents for enhancing the contrast in a diagnostic ultrasound procedure comprise colloidal dispersions of the liquid-in-liquid type, i.e., emulsions or microemulsions, in which the dispersed liquid phase is a liquid having a boiling point below the temperature of the animal to be imaged and which therefore undergoes a phase change from a dispersed liquid to a highly echogenic dispersed gaseous foam or kugelschaum following administration to the animal. The liquid state of the dispersed phase allows one to manufacture extremely stable, pharmaceutically acceptable emulsions with particle sizes typically below 1000 nm. The gaseous state at body temperature yields highly echogenic microbubbles, typically below 10,000 nm in diameter, which are effective as ultrasound contrast agents. Intravenous, intraarterial, oral, intraperitoneal, and intrauterine dosage forms, methods of administration, and imaging techniques are described.

Abstract: The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in utility for agents such as oligonucleotides which are plagued with problems in reaching targeted sites in necessary therapeutic levels. The delivery system includes gas-filled microbubbles formed in a nitrogen-free environment. Microbubbles formed through sonication in a nitrogen-free environment are smaller and more stable than microbubbles sonicated in the presence of room air.

Abstract: Ultrasonic visualisation of a subject, particularly of perfusion in the myocardium and other tissues, is performed using novel gas-containing contrast agent preparations which promote controllable and temporary growth of the gas phase in vivo following administration and can therefore act as deposited perfusion tracers. The preparations include a coadministerable composition comprising a diffusible component capable of inward diffusion into the dispersed gas phase to promote temporary growth thereof. In cardiac perfusion imaging the preparations may advantageously be coadministered with vasodilator drugs such as adenosine in order to enhance the differences in return signal intensity from normal and hypoperfused myocardial tissue respectively.

Abstract: One can impart outstanding resistance against collapse under pressure to gas-filled microvesicle used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003.

Abstract: Disclosed are injectable suspensions of gas filled microbubbles in an aqueous carrier liquid usable as contrast agents in ultrasonic echography. The suspensions comprise amphipathic compounds of which at least one may be a laminarized phospholipid as a stabilizer of the microbubbles against collapse with time and pressure. The concentration of phospholipids in the carrier liquid is below 0.01% wt but is at least equal to or above that at which phospholipid molecules are present solely at the gas microbubble-liquid interface. Also disclosed is a method of preparation of the stable suspensions of air or gas filled microbubbles.

Abstract: Improved methods for providing an image of an internal region of a patient. Embodiments of the invention involve the administration to the patient of a contrast agent which comprises, in an aqueous carrier, a lipid, protein, polymer or surfactant, and a gas. The patient is scanned using ultrasound imaging to obtain a visible image of the region. In embodiments of the invention, the scanning step may comprise applying a first quantity of ultrasound energy to the patient to provide a first image, followed by the application substantially immediately thereafter of a second quantity of ultrasound energy to provide a second image. The first and second images are then processed. The methods are particularly useful for obtaining on-line images of the cardiovascular region which may be employed, for example, to diagnose the presence of diseased tissue in the cardiovascular region of a patient.

Abstract: Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

Abstract: Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful both as efficacious contrast agents per se and as intermediates in the preparation of contrast agents wherein the phospholipids are crosslinked or polymerised. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

Abstract: Methods and compositions are provided for enhancing the bioadhesive properties of polymers used in drug delivery systems. The bioadhesive properties of a polymer are enhanced by incorporating an anhydride oligomer into the polymer to enhance the ability of the polymer to adhere to a tissue surface such as a mucosal membrane. Anhydride oligomers which enhance the bioadhesive properties of a polymer include oligomers synthesized from dicarboxylic acid monomers, preferably those found in Krebs glycolysis cycle, especially fumaric acid. The oligomers can be incorporated within a wide range of polymers including proteins, polysaccharides and synthetic biocompatible polymers. In one embodiment, anhydride oligomers can be incorporated within polymers used to form or coat drug delivery systems, such as microspheres, which contain a drug or diagnostic agent. The oligomers can either be solubilized and blended with the polymer before manufacture or else used as a coating with polymers over existing systems.

Abstract: The invention relates to gaseous microparticles for ultrasonic diagnosis, whose wall material is built up from block copolymers of polyesters of &agr;-, &bgr;- or &ggr;-hydroxycarboxylic acids with linear or star-shaped polyethylene glycols and optionally liquid crystals or whose wall material is built up from polyesters of &agr;-, &bgr;- or &ggr;-hydroxycarboxylic acids and liquid crystals, media that contain these particles for ultrasonic diagnosis, as well as a process for the production of the media and particles.

Abstract: Microballoons having a mean size in the range of 0.5 to 1000 microns bounded by a 50 to 500 nm thick biodegradable, interfacially deposited, synthetic polymer membrane which is both deformable and resilsient. These microballoons are used for ultrasonic echographic imaging of body organs.

Abstract: The foregoing invention relates to a new microbubble preparation and thrombolytic therapy which relies on microbubbles and ultrasound for its lytic activity. The pharmaceutical composition of the invention comprises a liquid solution of microbubbles with an internal atmosphere enhanced with the perfluorocarbon gas which cavitate in the presence of an ultrasound field following intravenous injection or infusion of said composition into said host. For thrombolysis the area of a thrombus is exposed to an ultrasound field in the presence of the microbubbles and significant lysis is experienced. The method and pharmaceutical composition of the invention exhibit thrombolytic properties similar to those of other thrombolytic agents such as urokinase and are less toxic and are clot specific in that they do not introduce a systemic lytic state to a said animal.

Abstract: Microparticles are provided comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microparticles contain a gas, liquid or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The microparticles are capable of passing through the capillary systems of a subject.

Abstract: A gas emulsion for ultrasound contrast enhancement comprising a plurality of gas bubbles in a liquid medium, the gas bubbles comprising at least one fluoroether selected from the group consisting of CF3OCF2OCF3, CF3(OCF2)2OCF3, CF3(OCF2)3OCF3, and CF3(OCF2)4OCF3.

Abstract: Microparticles useful for enhancing the ultrasound image of a tissue or organ consist of liquid and/or gas core material which is encapsulated by a biocompatible, tanned protein shell. These stabilized microparticles are useful as ultrasonic imaging agents, and are additionally useful in the further production of functionalized microparticles for in vivo imaging. In particular, targeting molecules such as antibodies or other ligands can be attached to the strengthened exterior surface of the stabilized microparticles to impart target-specificity to the microparticles. The targeting molecules may also provide hydrophilicity to the exterior surface, thus increasing the recirculation time of the microparticles. The targeting molecules may be attached directly to the exterior surface of the microparticles, or they may be attached via a bifunctional spacer arm, which may itself be hydrophilic.