Abstract: A foamed aqueous image enhancing composition containing cellulose and/or cellulose derivative(s), has a pH between 5.5 and 7, wherein the viscosity of the composition is less than 1800 mPa·sec, and wherein a gas is maintained in the composition for at least 1 minute after preparation. The combination of low viscosity and foam stability makes the composition particularly suitable in patency tests and fallopian tube sterilization checks.

Abstract: An apparatus for mass producing monodisperse microbubbles contains a microfluidic flow focusing device. The microfluidic flow focusing device includes a dispersed phase fluid supply channel having an outlet that discharges into a flow focusing junction, a continuous phase fluid supply channel having an outlet that discharges into the flow focusing junction, and a bubble formation channel having an inlet disposed at the flow focusing junction. The configuration of the flow focusing junction is such that, in operation, a flow of dispersed phase fluid discharging from the outlet of the dispersed phase fluid supply channel is engageable in co-flow by a focusing flow of continuous phase fluid discharging from the outlet of the at least one continuous phase fluid supply channel under formation of a gradually thinning jet of dispersed phase fluid that extends into the inlet of the bubble formation channel.

Abstract: This disclosure relates to a method for preparing organic microbubble complex particles including sonicating an aqueous solution including a graphene compound and an amphiphilic material in the presence of a gas, a method for preparing organic microbubble complex particles including injecting an aqueous solution including a graphene compound and an amphiphilic material into a microchannel, and an organic microbubble complex particle including a core part including at least one gas selected from the group consisting of an inert gas and carbon dioxide, and a shell layer including a graphene compound and an amphiphilic material, and an ultrasound contrast agent including the organic microbubble complex particles.

Abstract: The present invention provides methods for the preparation of gas-filled microbubbles, and methods of using for therapeutic and/or diagnostic applications. In particular, the methods of the invention allow for the preparation of gas-filled microbubbles having narrow size distributions and defined ultrasonic properties.

Abstract: The present invention generally relates to microbubble contrast agent compositions which are detectable by optical imaging methods, such as fluorescence, near-infrared or bioluminescence. Uses of the described compositions for imaging and therapeutic applications are contemplated.

Abstract: Provided herein is a composition, a method, and a system for delivering a functional molecule to the cytosol of a cell, comprising a liposome configured to be taken into a cell, including by a process selected from the group consisting of endocytosis, pinocytosis or phagocytosis, the liposome comprising a phase transforming liquid with vapor pressure capable of forming a gas at low pressure, said liquid being associated with the liposome, and the liposome further comprising at least one functional molecule selected from the group consisting of a therapeutic molecule, a detectable label, and a targeting molecule.

Abstract: The present invention provides reagents and methods for detecting cancer precancerous lesions in a patient.

Abstract: The present invention discloses a method for forming a nano-bubble. The forming method is different from the oil-water emulsion reaction in the prior art. The method comprises: taking an inorganic particle as a nucleus and performing a polymer coating process to coat at least one first polymer on the surface of the nucleus to form an organic/inorganic composite particle; then removing the nucleus of the organic/inorganic composite particle by way of the dissolution of a first solvent to form an impregnated nano-particle; performing a freeze-drying process to remove the first solvent to have the impregnated nano-particle form a hollow nano-particle; and finally dissolving the hollow nano-particle in a second solvent to form the nano-bubble.

Abstract: This invention addresses the clinical problem of how to optimize biological cell based therapies, such as stem cell therapy. Currently, cell therapies administered by intravenous, intra-arterial, and/or direct tissue injection are limited by the lack of clinically available imaging methods to detect the in vivo fate of the administered cells. There are many efforts underway to develop imaging strategies for stem cells in vivo, including radionuclide and MRI-based approaches. However, these approaches are limited by potential safety issues (e.g. radioactive exposure of stem cells, toxicity of iron particles used for MRI) and difficulty in serial tracking due to complex instrumentation and/or the requirement for repetitive radiation exposure.

Abstract: A microbubble is used as a multi-modality contrast agent for photoacoustic imaging and ultrasound imaging. A method of preparing improved microbubbles that are used as a multi-modality contrast agent for photoacoustic imaging and ultrasound imaging is provided. The microbubble includes a dye-colored lipid shell; and a filling gas filling the inside of the lipid shell. The method of preparing microbubbles includes agitating a dye-colored lipid-containing solution in the presence of filling gas.

Abstract: A microbubble ultrasound contrast agent for external use is provided. The microbubble ultrasound contrast agent applied externally can safely and efficiently enhance the permeation and absorption of the drug or small molecules in the local region of the body surface.

Abstract: The present invention relates to methods for the identification of a sentinel lymph node and to compounds and preparations used in said methods.

Abstract: A method of producing lipid-based micro/nano bubbles includes steps of (a) preparing a lipid mixture including one or more first lipids with different phase transition temperature, and a second lipid bonding with a hydrophilic polymer moiety or molecules capable of getting across a lipid membrane and decreasing van der Waals forces between lipid bilayers; (b) emulsifying the lipid mixture with a solvent, to form a transparent lipid carrier solution; (c) placing the transparent lipid carrier solution in a closed vessel with halo-substituted hydrocarbon; (d) manipulating temperature of the transparent lipid carrier solution to be close to a main phase transition temperature thereof; and (e) agitating in a mechanical manner the vessel containing the transparent lipid carrier solution to form micro/nano bubbles within the closed vessel. This method contributes to form micro/nano bubbles with desired diameters in a way of optimal material utilization efficiency.

Abstract: Provided are ultrasound imaging methods that include administering to a subject a contrast agent that includes a plurality of collapsible gas vesicles, obtaining ultrasound data of a target site of interest, and analyzing the ultrasound data to produce an ultrasound image of the target site. Ultrasound contrast agents are also provided. The subject methods and contrast agents find use in ultrasound imaging applications.

Abstract: The present invention provides compositions useful for transfecting cells (e.g., liver cells) to express ABCA1. The compositions described herein comprise a pharmaceutically acceptable aqueous carrier containing sonochemically-active microspheres together with a plasmid DNA construct encoding an active form of ABCA1 and at least one promoter for the expression thereof. Preferably, the sonochemically-active microspheres comprise, consist essentially of, or consist of gas bubbles (e.g., a fluorocarbon gas, such as octafluoropropane) encapsulated within protein-containing or lipid-containing shells (e.g., human serum albumin shells). The microspheres are disruptable by exposure to ultrasonic acoustic energy to release the encapsulated gas.

Abstract: The present invention relates to a microbubble comprising a monolayer of porphyrin-phospholipid conjugate, said microbubble having encapsulated therein, and to the use of said microbubble in ultrasound imaging of a target area in a subject.

Abstract: The invention provides compositions and methods for therapeutic and diagnostic applications.

Abstract: The present invention provides polypeptides, peptide dimers, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD<1 ?M), and dimer and multimeric constructs comprising these polypeptides, particularly contrast agents. Also provided are methods for monitoring and evaluating the therapeutic effectiveness of treatment protocols for diseases associated with angiogenesis or endothelial cell hyperproliferation, such as cancer, using contrast agents of the invention.

Abstract: The present invention is directed to a stable fluorocarbon emulsion having a continuous aqueous phase and discontinuous fluorocarbon phase comprising two fluorocarbons and surprisingly demonstrates that perfluorodecyl bromide is as effective in stabilizing perfluorooctyl bromide emulsions of certain concentrations than much more highly concentrated perfluorooctyl bromide/perfluorodecyl bromide emulsions without the significant problems experienced in higher concentrated emulsions such as longer organ retention times, formation of PFDB crystals, larger emulsion particles, manufacturing problems and inability of repeat dosing inherent with higher concentrations of perfluorodecyl bromide.

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: A stabilized nanobubble can include a membrane that defines at least one internal void, which includes at least one gas. The membrane can include at least one lipid and at least one nonionic triblock copolymer that is effective to control the size of the nanobubble without compromising in vitro and in vivo echogenicity of the nanobubble.

Abstract: The present invention relates to a perfluorocarbon nanoemulsion containing quantum dot nanoparticles and a method for preparing the same, more specifically, relates to a method for preparing a multifunctional perfluorocarbon nanoemulsion which simultaneously shows the fluorine-based magnetic resonance properties of perfluorocarbon and the optical properties of quantum dot nanoparticles, the method comprising dispersing quantum dot nanoparticles, modified with a fluorine end group, in perfluorocarbon, and then adding an aqueous emulsifier solution containing lipid to the dispersion. The disclosed perfluorocarbon nanoemulsion containing quantum dot nanoparticles has excellent biocompatibility and simultaneously shows optical properties and magnetic resonance properties, and thus can be used as a contrast agent for multi-mode molecular imaging. Accordingly, the nanoemulsion can be used to study cell and small-animal molecular imaging in various fields, including biological and medical fields.

Abstract: Disclosed is a liver tumor-targeting ultrasound contrast agent. The ultrasound contrast agent includes a gas-generating core and a hyaluronic acid shell. The ultrasound contrast agent can be specifically delivered to liver cells. This specific delivery enables easy differentiation between normal liver cells and liver tumor cells by ultrasound imaging. In addition, the ultrasound contrast agent is highly stable in aqueous condition and causes no cytotoxicity. Also disclosed is a method for preparing the ultrasound contrast agent.

Abstract: Embodiments of the invention include a system comprising: an Acetoxy curable silicone Binder; and an active agent blended with the silicone binder, effective for one or more of radiopacification, lubricity, elution of a secondary compound such as a drug, echogenic properties, thermal or electrically insulative properties or chemical indicators wherein the silicone binder effectiveness is not substantially changed by the active 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: Method and medical devices for generating and stabilizing micro- or nano-bubbles, and systems and methods for therapeutic applications using the bubbles, are provided. The micro-bubbles may be used to enhance therapeutic benefits such as ultrasound-guided precision drug delivery and real-time verification, acoustic activation of large tumor masses, enhanced acoustic activation through longer retention of therapeutic agents at the point of interest, enhancement of high intensity focused ultrasound treatments, light activation of photodynamic drugs at a depth within a patient using extracorporeal light sources, probes, or sonoluminescence, and initiation of time reversal acoustics focused ultrasound to permit highly localized treatment.

Abstract: The present invention provides polypeptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD<1 ?M), and dimer and multimeric constructs comprising these polypeptides.

Abstract: A method and related system for providing therapy to a treatment site, such as stenosis or other vasculature disease, at one or more locations of a subject, such as the vasculature. The method includes: advancing an ultrasound catheter to or in proximity to the subject's treatment site; infusing microbubbles into or proximal to the treatment site; and delivering ultrasonic energy from the ultrasound catheter. The ultrasonic energy may be adapted for: imaging the treatment site, translating the microbubbles into or in the vicinity of the treatment site and/or rupturing the microbubbles.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: Methods and compositions for using tumor targeting compounds bound to microbubbles to facilitate drug delivery and diagnostic imaging at tumor sites.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: Compositions useful for target detection, imaging and treatment, as well as methods of production and use thereof, are disclosed herein.

Abstract: An apparatus, system or method enables microbubbles to be created on demand for use as the contrast agent within a contrast medium administrable to a patient for purposes of a medical procedure. The system comprises a reservoir, a pressurizing device, a microbubble generator, and a controller. The reservoir stores a liquid. The pressurizing device conveys the liquid, along with the medium formed therewith, through the system. The microbubble generator is used to create the microbubbles within the liquid to form the medium. The microbubble generator has an inlet for receiving the liquid and an outlet for communication of the medium to the patient. The controller controls the operation of the system so that the microbubbles created by the microbubble generator are generated according to the demands of the medical procedure and are administrable within the medium to the patient.

Abstract: Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging.

Abstract: Methods and compositions for the site-selective delivery of a gene to a site within the body of an animal where virus not encapsulated within the microbubbles is inactivated, for example by treatment with a virus-inactivating agent.

Abstract: The present invention relates to the fabrication and use of microbubbles. In some embodiments, the invention provides for the fabrication and use of polymerized shell lipid microbubbles (PSMs). The microbubbles of the invention can be used, for example, for diagnosis and treatment of a condition.

Abstract: Flow cytometry concepts are modified to enable dynamic characterizations of particles to be obtained using optical scattering data. Particles in flow will be introduced into a sample volume. Light scattered by a particle in the sample volume is collected and analyzed. What differentiates the concepts disclosed herein from conventional flow cytometry is the use of an acoustic source that is disposed to direct acoustic energy into the sample volume. As the particle passes through the sample volume, it responds to the acoustic energy, causing changes in the light scattered by the particle. Those changes, which are not measured during conventional flow cytometry, can be analyzed to determine additional physical properties of the particle.

Abstract: The invention is directed to injectable suspensions of gas-filled microvesicles, as well as methods of preparing and using the same, especially as ultrasound contrast agents.

Abstract: Injectable aqueous suspension of microbubbles filled with a biocompatible gas and a method of preparation thereof. At least 10% of the total volume of gas contained in the microbubbles is contained in microbubbles with a diameter of 1.5 ?m or less. The microbubbles can be obtained by preparing an emulsion comprising an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and then reconstituted in an aqueous suspension of gas-filled microbubbles.

Abstract: Targeted microbubbles are generated by post-labeling buried ligand microbubbles. According to embodiments, buried ligand microbubbles are created with steric brushes protecting functionalized polymer tethers. Ligands were attached to the functionalized tethers by diffusion of ligands of a small size through the steric barrier. The steric barrier was substantially capable of hindering access to the tethers by larger molecules. The embodiments disclosed include methods for creating microbubble batches that can be loaded with selected ligands, for titrating the targeting ligands thereby to reduce waste and cost, and for using resulting buried ligand molecules for medical purposes.

Abstract: Anti-ICAM-1 VHH single-domain antibodies (sdAbs) are generated by immunizing a llama with recombinant ICAM-1. These antibodies are linked to an imaging moiety for in vivo or ex vivo imaging of ICAM-1-related pathological conditions including atherosclerotic plaques. The antibodies may also be linked to a therapeutic agent to specifically target and treat ICAM-1-related pathological conditions.

Abstract: The invention encompasses radiopharmaceutical compounds that can be used in imaging cell death associated with either apoptosis or necrosis. Phosphatidylethanolamine (PtdE) is externalized to the surface of apoptotic cells, and also becomes accessible in necrotic cells due to compromised plasma membrane integrity. Duramycin, a 19 amino acid polypeptide, binds PtdE at a 1:1 ratio with high affinity and exclusive specificity. Novel Duramycin-based radiopharmaceuticals and non-radioactively labeled compounds are disclosed herein. Such compounds facilitate detection of cell apoptosis and/or necrosis by binding to PtdE. The location of the bound compound can then be pinpointed using standard imaging techniques.

Abstract: A method of forming a plurality of microbubbles, wherein the method disposes in a sealed container comprising a first volume at ambient pressure, a second volume of a mixture comprising one or more microbubble stabilizing materials. The first volume is greater than said second volume. The method further comprises sealing said container, introducing a gas into said sealed container, and shaking the container to form said plurality of microbubbles.

Abstract: Provided herein are novel compositions comprising DEspR-specific antagonists and agonists, and methods of their use in a variety of therapeutic applications. The compositions comprising the DEspR-specific anatgonists and agonists described herein are useful in therapeutic, diagnostic and imaging methods, such as DEspR-targeted molecular imaging of angiogenesis, and for companion diagnostic and/or in vivo-non invasive imaging and/or assessments.

Abstract: Fibrin-binding peptides having high binding affinity and excellent physical characteristics compared to previously known fibrin-binding peptides are provided. These fibrin-binding peptides may be conjugated to a detectable label or a therapeutic agent and used to detect and facilitate treatment of pathological conditions associated with the presence of fibrin such as thrombic, angiogenic and neoplastic conditions. These peptides may be used in imaging processes such as MRI, ultrasound and nuclear medicine imaging (e.g. PET, scintigraphic imaging, etc.). The peptides may also be used therapeutically. The present invention also provides processes and methods for making and using such peptides and conjugates thereof.

Abstract: An ultrasound contrast agent composed of at least one kind of low-boiling water-insoluble substance (with a boiling point lower than 37° C.) and at least one kind of high-boiling water-insoluble substance (with a boiling point higher than 37° C.). The former vaporizes to absorb ultrasonic energy upon application of ultrasound, thereby causing the latter to vaporize secondarily, with the resulting bubbles producing an echo image. It is less liable to bumping and hence safe.

Abstract: Flow cytometry concepts are modified to enable dynamic characterizations of particles to be obtained using optical scattering data. Particles in flow will be introduced into a sample volume. Light scattered by a particle in the sample volume is collected and analyzed. What differentiates the concepts disclosed herein from conventional flow cytometry is the use of an acoustic source that is disposed to direct acoustic energy into the sample volume. As the particle passes through the sample volume, it responds to the acoustic energy, causing changes in the light scattered by the particle. Those changes, which are not measured during conventional flow cytometry, can be analyzed to determine additional physical properties of the particle.

Abstract: Medical apparatus and processes controllably generate medically useful micro or nano bubbles of medically desirable and controllably selectable size, size distribution, homogeneity and concentration (and/or other key bubble parameters) for patient infusion, and/or which may incorporate therapeutic or other agents for patient infusion and/or may be combined with therapeutic or other agents prior to infusion into patients. The bubble generation apparatus and processes controllably permit the adjustment and selection of key bubble parameters through bubble generation actuation and orientation techniques and through selection of bubble fluid compositions in order to facilitate medical research and/or to optimize treatment for imaging, therapy, sonoporation, inertial and non-inertial cavitation, and acoustic activation, among other medical uses. Disposable cartridges containing such bubbles are provided and may include means for patient infusion.

Abstract: A catheter system including an elongate tubular member having a proximal end portion, a distal end portion and a lumen extending through at least a portion of a length of the elongate tubular member. The distal end portion of the elongate member is dimensioned and adapted to advance to or in proximity to a treatment site of a subject. A microbubble device is in fluid communication with the lumen. The microbubble device includes at least one input port for receiving a flow of material into the device and an output port configured to output microbubbles from the microbubble device. A second tubular member is in fluid communication with one of the at least one input ports. A pressure fitting arrangement is adapted to maintain a seal between the second tubular member and the input port.

Abstract: The invention provides a composition comprising microparticles of a water-insoluble or poorly soluble compound, at least one phospholipid, and at least one surfactant, produced by applying an energy to a mixture comprising particles of the compound, the at least one phospholipid, and the at least one surfactant so as to obtain the microparticles. The invention also provides a process for preparing microparticles of a water-insoluble or poorly soluble compound. The process includes mixing particles of a water-insoluble or poorly soluble compound with at least one phospholipid and at least surfactant to form a mixture and applying energy to the mixture sufficient to produce microparticles of the compound. The methods of the invention allow for the production of microparticles smaller than particles produced through previously known methods and the microparticles exhibit advantageous properties including remarkable resistance to particle size growth during storage.