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Alexander L Klibanov - One of the best experts on this subject based on the ideXlab platform.
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In vivo imaging of microfluidic-produced Microbubbles
Biomedical Microdevices, 2015Co-Authors: Ali H. Dhanaliwala, Alexander L Klibanov, Adam J. Dixon, Johnny L. Chen, John A. HossackAbstract:Microfluidics-based production of stable Microbubbles for ultrasound contrast enhancement or drug/gene delivery allows for precise control over microbubble diameter but at the cost of a low production rate. In situ microfluidic production of Microbubbles directly in the vasculature may eliminate the necessity for high microbubble production rates, long stability, or small diameters. Towards this goal, we investigated whether microfluidic-produced Microbubbles directly administered into a mouse tail vein could provide sufficient ultrasound contrast. Microbubbles composed of nitrogen gas and stabilized with 3 % bovine serum albumin and 10 % dextrose were injected for 10 seconds into wild type C57BL/6 mice, via a tail-vein catheter. Short-axis images of the right and left ventricle were acquired at 12.5 MHz and image intensity over time was analyzed. Microbubbles were produced on the order of 10^5 Microbubbles/s and were observed in both the right and left ventricles. The median rise time, duration, and decay time within the right ventricle were 2.9, 21.3, and 14.3 s, respectively. All mice survived the procedure with no observable respiratory or heart rate distress despite microbubble diameters as large as 19 μ m.
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Microbubbles as ultrasound contrast agents for molecular imaging preparation and application
American Journal of Roentgenology, 2012Co-Authors: Sunil Unnikrishnan, Alexander L KlibanovAbstract:OBJECTIVE. The purpose of this review is to describe trends in microbubble application in molecular imaging. CONCLUSION. Microbubbles are used for contrast ultrasound imaging as blood-pool agents in cardiology and radiology. Their promise as targeted agents for molecular imaging is now being recognized. Microbubbles can be functionalized with ligand molecules that bind to molecular markers of disease. Potential clinical applications of molecular imaging with microbubble-based ultrasound contrast agents are in the monitoring of the biomarker status of vascular endothelium, visualizing tumor vasculature, and imaging inflammation and ischemia-reperfusion injury zones and thrombi.
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ultrasound triggered release of materials entrapped in microbubble liposome constructs a tool for targeted drug delivery
Journal of Controlled Release, 2010Co-Authors: Alexander L Klibanov, Talent I Shevchenko, Balasundar Iyyavu Raju, Ralf Seip, Chien Ting ChinAbstract:Abstract We investigated the preparation of ultrasound-triggered drug delivery system, based on a pendant complex of microbubble coated with liposomes. Biotinylated decafluorobutane Microbubbles were coated with biotinylated liposomes via a streptavidin linker. Liposomes were prepared incorporating calcein and thrombin. Based on initial concentration of calcein, over 1 um3 payload volume per each microbubble–liposome particle was achieved, when 100 nm liposomes were used. Insonation of microbubble–liposome pendants in vitro resulted in the complete destruction of Microbubbles and triggered release of a significant fraction of the entrapped material. Treatment with 1 MHz ultrasound (5 pulses, 100 ms, 7 MPa peak negative acoustic pressure) resulted in the release of ~ 30% of entrapped calcein, as estimated by the fluorescence quenching assay. Thrombin release from liposomes complexed with Microbubbles (11% of entrapped material) due to ultrasound treatment was estimated by a chromogenic substrate study. Prior to insonation, substrate hydrolysis was at background level. Ultrasound-triggered release of thrombin from the pendant complexes caused an acceleration of blood clotting.
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microbubble contrast agents targeted ultrasound imaging and ultrasound assisted drug delivery applications
Investigative Radiology, 2006Co-Authors: Alexander L KlibanovAbstract:Abstract:The use of microbubble contrast agents for general tissue delineation and perfusion enjoys steady interest in ultrasound imaging. Microbubbles as contrast materials require a small dosage and show excellent detection sensitivity. Targeting ligands on the surface of Microbubbles permit the s
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acoustic radiation force enhances targeted delivery of ultrasound contrast Microbubbles in vitro verification
IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control, 2005Co-Authors: Joshua J Rychak, Alexander L Klibanov, John A. HossackAbstract:Recent research has shown that targeted ultrasound contrast Microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that acoustic radiation can be used to force free-stream Microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of Microbubbles. Lipid Microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 /spl times/ 10/sup 6/ to 75 /spl times/ 10/sup 6/ ml/sup -1/. Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s/sup -1/, suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.
Gary H Brandenburger - One of the best experts on this subject based on the ideXlab platform.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives: During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin–biotin interaction under microscopy control and subjected to ultrasound imaging. Results: Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual Microbubbles as determined by Coulter. Individual Microbubbles immobilized on polystyrene were also visualized by ultrasound. Conclusion: Ultrasound medical systems can resolve backscatter signals from individual Microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives:During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles
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Destruction of contrast agent Microbubbles in the ultrasound field: the fate of the microbubble shell and the importance of the bubble gas content.
Academic Radiology, 2002Co-Authors: Alexander L Klibanov, Michael S Hughes, Jolette K Wojdyla, James H Wible, Gary H BrandenburgerAbstract:Disappearance of ultrasound (US) contrast agents (gasfilled Microbubbles) after contrast agent administration in the bloodstream occurs by way of several mechanisms. First, Microbubbles are filtered and captured by various organs, including uptake by Kupffer cells in the liver (1,2). Second, gas diffuses from the microbubble core and dissolves in the surrounding medium, leaving the nonechogenic shell behind (3). The third process is the most rapid and important for the practice of diagnostic imaging by US. It is the destruction of Microbubbles by the acoustic field of the US medical imaging system. It has been shown that the rate of microbubble destruction in the ultrasound field depends on the ultrasound frequency and pressure (4–7). During imaging, the microbubble contrast agent can be destroyed by a single pulse of the ultrasound, if the ultrasound mechanical index (MI) value is high enough (7,8). This phenomenon has been applied successfully for the imaging of tissue perfusion and perfusion defects (8,9). Thus, the mechanisms of microbubble contrast agent disappearance in the ultrasound field are important and need to be investigated in detail. We have previously reported a microbubble destruction/microscopy study performed with an air-filled microbubble agent, sonicated human serum albumin (Albunex; Mallinckrodt, St Louis, Mo) (10). More recent contrast agents filled with insoluble fluorinated gases, such as Optison (Mallinckrodt), demonstrate extended in vivo circulation and stability (11). It is of interest to evaluate the stability of these Microbubbles in the field of the US medical imager. The nature of the gas and the gas exchange may play an important role in the bubble destruction. Here, we describe video microscopic studies performed in vitro for immobilized Microbubbles during their insonification. Fluorescence microscopy was used to evaluate the behavior of microbubble shells during the destruction of Microbubbles.
Michael S Hughes - One of the best experts on this subject based on the ideXlab platform.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives: During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin–biotin interaction under microscopy control and subjected to ultrasound imaging. Results: Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual Microbubbles as determined by Coulter. Individual Microbubbles immobilized on polystyrene were also visualized by ultrasound. Conclusion: Ultrasound medical systems can resolve backscatter signals from individual Microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives:During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles
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Destruction of contrast agent Microbubbles in the ultrasound field: the fate of the microbubble shell and the importance of the bubble gas content.
Academic Radiology, 2002Co-Authors: Alexander L Klibanov, Michael S Hughes, Jolette K Wojdyla, James H Wible, Gary H BrandenburgerAbstract:Disappearance of ultrasound (US) contrast agents (gasfilled Microbubbles) after contrast agent administration in the bloodstream occurs by way of several mechanisms. First, Microbubbles are filtered and captured by various organs, including uptake by Kupffer cells in the liver (1,2). Second, gas diffuses from the microbubble core and dissolves in the surrounding medium, leaving the nonechogenic shell behind (3). The third process is the most rapid and important for the practice of diagnostic imaging by US. It is the destruction of Microbubbles by the acoustic field of the US medical imaging system. It has been shown that the rate of microbubble destruction in the ultrasound field depends on the ultrasound frequency and pressure (4–7). During imaging, the microbubble contrast agent can be destroyed by a single pulse of the ultrasound, if the ultrasound mechanical index (MI) value is high enough (7,8). This phenomenon has been applied successfully for the imaging of tissue perfusion and perfusion defects (8,9). Thus, the mechanisms of microbubble contrast agent disappearance in the ultrasound field are important and need to be investigated in detail. We have previously reported a microbubble destruction/microscopy study performed with an air-filled microbubble agent, sonicated human serum albumin (Albunex; Mallinckrodt, St Louis, Mo) (10). More recent contrast agents filled with insoluble fluorinated gases, such as Optison (Mallinckrodt), demonstrate extended in vivo circulation and stability (11). It is of interest to evaluate the stability of these Microbubbles in the field of the US medical imager. The nature of the gas and the gas exchange may play an important role in the bubble destruction. Here, we describe video microscopic studies performed in vitro for immobilized Microbubbles during their insonification. Fluorescence microscopy was used to evaluate the behavior of microbubble shells during the destruction of Microbubbles.
James H Wible - One of the best experts on this subject based on the ideXlab platform.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives: During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin–biotin interaction under microscopy control and subjected to ultrasound imaging. Results: Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual Microbubbles as determined by Coulter. Individual Microbubbles immobilized on polystyrene were also visualized by ultrasound. Conclusion: Ultrasound medical systems can resolve backscatter signals from individual Microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives:During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles
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Destruction of contrast agent Microbubbles in the ultrasound field: the fate of the microbubble shell and the importance of the bubble gas content.
Academic Radiology, 2002Co-Authors: Alexander L Klibanov, Michael S Hughes, Jolette K Wojdyla, James H Wible, Gary H BrandenburgerAbstract:Disappearance of ultrasound (US) contrast agents (gasfilled Microbubbles) after contrast agent administration in the bloodstream occurs by way of several mechanisms. First, Microbubbles are filtered and captured by various organs, including uptake by Kupffer cells in the liver (1,2). Second, gas diffuses from the microbubble core and dissolves in the surrounding medium, leaving the nonechogenic shell behind (3). The third process is the most rapid and important for the practice of diagnostic imaging by US. It is the destruction of Microbubbles by the acoustic field of the US medical imaging system. It has been shown that the rate of microbubble destruction in the ultrasound field depends on the ultrasound frequency and pressure (4–7). During imaging, the microbubble contrast agent can be destroyed by a single pulse of the ultrasound, if the ultrasound mechanical index (MI) value is high enough (7,8). This phenomenon has been applied successfully for the imaging of tissue perfusion and perfusion defects (8,9). Thus, the mechanisms of microbubble contrast agent disappearance in the ultrasound field are important and need to be investigated in detail. We have previously reported a microbubble destruction/microscopy study performed with an air-filled microbubble agent, sonicated human serum albumin (Albunex; Mallinckrodt, St Louis, Mo) (10). More recent contrast agents filled with insoluble fluorinated gases, such as Optison (Mallinckrodt), demonstrate extended in vivo circulation and stability (11). It is of interest to evaluate the stability of these Microbubbles in the field of the US medical imager. The nature of the gas and the gas exchange may play an important role in the bubble destruction. Here, we describe video microscopic studies performed in vitro for immobilized Microbubbles during their insonification. Fluorescence microscopy was used to evaluate the behavior of microbubble shells during the destruction of Microbubbles.
Jolette K Wojdyla - One of the best experts on this subject based on the ideXlab platform.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives: During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin–biotin interaction under microscopy control and subjected to ultrasound imaging. Results: Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual Microbubbles as determined by Coulter. Individual Microbubbles immobilized on polystyrene were also visualized by ultrasound. Conclusion: Ultrasound medical systems can resolve backscatter signals from individual Microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.
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detection of individual Microbubbles of ultrasound contrast agents imaging of free floating and targeted bubbles
Investigative Radiology, 2004Co-Authors: Alexander L Klibanov, Peter T Rasche, Michael S Hughes, Jolette K Wojdyla, Karen P Galen, James H Wible, Gary H BrandenburgerAbstract:Rationale and Objectives:During echo examinations with microbubble contrast, individual “dots” of ultrasound reflection can be visualized. To address the question whether these signals represent individual Microbubbles, very dilute suspensions of ultrasound contrast agents or individual Microbubbles
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Destruction of contrast agent Microbubbles in the ultrasound field: the fate of the microbubble shell and the importance of the bubble gas content.
Academic Radiology, 2002Co-Authors: Alexander L Klibanov, Michael S Hughes, Jolette K Wojdyla, James H Wible, Gary H BrandenburgerAbstract:Disappearance of ultrasound (US) contrast agents (gasfilled Microbubbles) after contrast agent administration in the bloodstream occurs by way of several mechanisms. First, Microbubbles are filtered and captured by various organs, including uptake by Kupffer cells in the liver (1,2). Second, gas diffuses from the microbubble core and dissolves in the surrounding medium, leaving the nonechogenic shell behind (3). The third process is the most rapid and important for the practice of diagnostic imaging by US. It is the destruction of Microbubbles by the acoustic field of the US medical imaging system. It has been shown that the rate of microbubble destruction in the ultrasound field depends on the ultrasound frequency and pressure (4–7). During imaging, the microbubble contrast agent can be destroyed by a single pulse of the ultrasound, if the ultrasound mechanical index (MI) value is high enough (7,8). This phenomenon has been applied successfully for the imaging of tissue perfusion and perfusion defects (8,9). Thus, the mechanisms of microbubble contrast agent disappearance in the ultrasound field are important and need to be investigated in detail. We have previously reported a microbubble destruction/microscopy study performed with an air-filled microbubble agent, sonicated human serum albumin (Albunex; Mallinckrodt, St Louis, Mo) (10). More recent contrast agents filled with insoluble fluorinated gases, such as Optison (Mallinckrodt), demonstrate extended in vivo circulation and stability (11). It is of interest to evaluate the stability of these Microbubbles in the field of the US medical imager. The nature of the gas and the gas exchange may play an important role in the bubble destruction. Here, we describe video microscopic studies performed in vitro for immobilized Microbubbles during their insonification. Fluorescence microscopy was used to evaluate the behavior of microbubble shells during the destruction of Microbubbles.