Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging

Zhao, Shan; Borden, Mark A.; Bloch, Susannah H.; Kruse, Dustin E.; Ferrara, Katherine W.; Dayton, Paul A.

doi:10.1162/1535350042380317

Cited by 160 publications

(93 citation statements)

References 23 publications

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“…In contrast to surfactant-coated microbubbles, lipid-coated microbubbles have been shown to be stable after centrifugation up to several hundred RCF [26,27]. The lipid shell is highly viscous [28] and relatively impermeable to gases [29].…”

Section: Introductionmentioning

confidence: 99%

Microbubble size isolation by differential centrifugation

Feshitan

Chen

Kwan

et al. 2009

Journal of Colloid and Interface Science

401

381

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Section: Introductionmentioning

confidence: 99%

Microbubble size isolation by differential centrifugation

Feshitan

Chen

Kwan

et al. 2009

Journal of Colloid and Interface Science

401

381

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“…The preparation of the targeted microbubbles and avidin-coated microtube have been described previously. 19 Buoyancy was used to locate microbubbles such that they bound in the plane parallel to the imaging view [ Fig. 1(a)].…”

mentioning

confidence: 99%

Asymmetric oscillation of adherent targeted ultrasound contrast agents

Zhao¹,

Ferrara²,

Dayton³

2005

Appl. Phys. Lett.

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With a lipid shell containing biotin, micron-sized bubbles bound to avidin on a porous and flexible cellulose boundary were insonified by ultrasound. The oscillation of these targeted microbubbles was observed by high-speed photography and compared to the oscillation of free-floating microbubbles. Adherent microbubbles were observed to oscillate asymmetrically in the plane normal to the boundary, and nearly symmetrically in the plane parallel to the boundary, with a significantly smaller maximum expansion in each dimension for bound than free bubbles. With sufficient transmitted pressure, a jet was produced traveling toward the boundary.There is a great interest in developing molecularly targeted ultrasound contrast agents due to the potential medical applications. [1][2][3][4] The agents are gas bubbles with a diameter on the order of a few microns and a shell of albumin, lipid, or polymer. After intravenous injection, peptides or antibodies attached to the shells link the agents to a receptor on endothelial cells. Because of their high echogencity, these targeted agents can be detected by an ultrasound system with high sensitivity, and therefore can provide important information such as the spatial distribution and extent of tumor angiogenesis, 5,6 inflammatory response, 7,8 or thrombus. 9 Current contrast imaging schemes are not yet optimized for imaging these targeted agents because the microbubbles retained in tissue are limited in number, 5,9 and the signal from adherent microbubbles can be masked by the signal from freely circulating microbubbles. Strategies for imaging these agents currently require waiting for clearance of free-floating microbubbles or employing image averaging and subtraction techniques. Neither of these techniques is optimal since they require either a time delay, or multiple frames, which impede real-time imaging. Hence, there is a need for the development of a new selective and sensitive method for detecting adherent microbubbles, which will depend on our understanding of the acoustic behavior of a targeted microbubble after it binds to a targeting site.Mathematical simulations have been developed for modeling microbubble radial oscillation with different assumptions and simplifications. [10][11][12] High-speed micrography has been used to study microbubble radial oscillation, 13 translation, 14 and fragmentation. 15 In these studies, a microbubble is assumed to remain spherical and in an infinite medium. Asymmetrical oscillation of a cavitation bubble and formation of a jet have been studied both theoretically and experimentally by a number of research groups, [16][17][18] although previous experimental studies have involved unencapsulated bubbles of a diameter larger than micron-sized contrast agents, and have not used ultrasound as an excitation source. The behavior of a targeted microbubble after it binds to a vessel wall and is insonified by an ultrasound pulse has not been reported previously. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn...

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“…This radiation force technique is used to deliver particles away from the center of the flow in a vessel so they could touch the target surface. Targeting efficacy, especially in the fast flow conditions (wall shear stress [0.2 Pa, when antibodymediated targeting is often completely inefficient) is improved by nearly two orders of magnitude [37,40,51].…”

Section: Improving Microbubble Targeting: Biomechanics Considerationsmentioning

confidence: 99%

Preparation of targeted microbubbles: ultrasound contrast agents for molecular imaging

Klibanov

2009

Med Biol Eng Comput

121

105

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Targeted ultrasound contrast agents can be prepared by attaching targeting ligands to the lipid, protein or polymer shell coating of gas-filled microbubbles. These materials are stable on storage, fully biocompatible and can be administered parenterally. Detection of microbubble contrast agents by ultrasound is very efficient (single particles with picogram mass can be visualized). Covalent or noncovalent binding techniques can be used to attach targeting ligands. Ligand-carrying microbubbles adhere to the respective molecular targets in vitro and in vivo. Several biomechanical methods are available to improve targeting efficacy, such as the use of a flexible tether spacer arm between the ligand and the bubble, and the use of folds on the microbubble shell, that project out, enhancing the contact area and increasing the length of the lever arm.

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Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging

Cited by 160 publications

References 23 publications

Microbubble size isolation by differential centrifugation

Microbubble size isolation by differential centrifugation

Asymmetric oscillation of adherent targeted ultrasound contrast agents

Preparation of targeted microbubbles: ultrasound contrast agents for molecular imaging

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