Ultrasound Contrast Materials in Cardiovascular Medicine: from Perfusion Assessment to Molecular Imaging

Klibanov, Alexander L.

doi:10.1007/s12265-013-9501-0

Cited by 15 publications

(14 citation statements)

References 61 publications

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“…U LTRASOUND contrast agents that consist of targeted microbubbles are emerging in their applications for ultrasound molecular imaging [1]- [3]. These microbubbles have a ligand attached to their shell by which they can be targeted to a specific biomarker, for example, α v β 3 that is expressed on the cellular membrane of endothelial cells in neovasculature [4], [5]. For successful translation of ultrasound molecular imaging to the clinic, two major problems still need to be tackled: 1) producing microbubbles of the same size that also behave identical in an ultrasound field and 2) distinguishing the response of a single targeted microbubble bound to a specific biomarker from a nonbound targeted microbubble.…”

Section: Introductionmentioning

confidence: 99%

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

Rooij

Beekers

Lattwein

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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One of the main challenges for ultrasound molecular imaging is acoustically distinguishing nonbound microbubbles from those bound to their molecular target. In this in vitro study, we compared two types of in-house produced targeted lipid-coated microbubbles, either consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, C16:0 (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine, C18:0 (DSPC) as the main lipid, using the Brandaris 128 ultrahigh-speed camera to determine vibrational response differences between bound and nonbound biotinylated microbubbles. In contrast to previous studies that studied vibrational differences upon binding, we used a covalently bound model biomarker (i.e., streptavidin) rather than physisorption, to ensure binding of the biomarker to the membrane. The microbubbles were insonified at frequencies between 1 and 4 MHz at pressures of 50 and 150 kPa. This paper shows lower acoustic stability of bound microbubbles, of which DPPC-based microbubbles deflated most. For DPPC microbubbles with diameters between 2 and [Formula: see text] driven at 50 kPa, resonance frequencies of bound microbubbles were all higher than 1.8 MHz, whereas those of nonbound microbubbles were significantly lower. In addition, the relative radial excursions at resonance were also higher for bound DPPC microbubbles. These differences did not persist when the pressure was increased to 150 kPa, except for the acoustic stability which further decreased. No differences in resonance frequencies were observed between bound and nonbound DSPC microbubbles. Nonlinear responses in terms of emissions at the subharmonic and second harmonic frequencies were similar for bound and nonbound microbubbles at both pressures. In conclusion, we identified differences in vibrational responses of bound DPPC microbubbles with diameters between 2 and [Formula: see text] that distinguish them from nonbound ones.

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Section: Introductionmentioning

confidence: 99%

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

Rooij

Beekers

Lattwein

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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“…For over three decades, UCAs have been clinically used to enhance ultrasound (US) imaging in different fields, such as cardiology and radiology [1,2]. Targeted UCAs (tUCAs) differ from clinically approved UCAs by the decoration of their shell with targeting ligands [3]. Due to their typical size ($1-10 mm) UCAs are confined to the blood pool only [4,5].…”

Section: Introductionmentioning

confidence: 99%

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Rooij

Daeichin

Skachkov

et al. 2015

International Journal of Hyperthermia

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Ultrasound contrast agents (UCAs) are used routinely in the clinic to enhance contrast in ultrasonography. More recently, UCAs have been functionalised by conjugating ligands to their surface to target specific biomarkers of a disease or a disease process. These targeted UCAs (tUCAs) are used for a wide range of pre-clinical applications including diagnosis, monitoring of drug treatment, and therapy. In this review, recent achievements with tUCAs in the field of molecular imaging, evaluation of therapy, drug delivery, and therapeutic applications are discussed. We present the different coating materials and aspects that have to be considered when manufacturing tUCAs. Next to tUCA design and the choice of ligands for specific biomarkers, additional techniques are discussed that are applied to improve binding of the tUCAs to their target and to quantify the strength of this bond. As imaging techniques rely on the specific behaviour of tUCAs in an ultrasound field, it is crucial to understand the characteristics of both free and adhered tUCAs. To image and quantify the adhered tUCAs, the state-of-the-art techniques used for ultrasound molecular imaging and quantification are presented. This review concludes with the potential of tUCAs for drug delivery and therapeutic applications.

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“…Cette propriété est mise à profit pour évaluer la cinétique de perfusion d'organes ou de tumeurs : les microbulles sont injectées, traduites en images à faible puissance ultrasonore, détruites localement dans une région d'intérêt grâce aux ultrasons, puis l'arrivée de nouvelles bulles non détruites est mise en image et quantifiée [21]. Certains travaux actuels portent sur la décoration des microbulles à l'aide de ligands spécifiques de récepteurs afin de réaliser de l'imagerie moléculaire [22]. En général le ligand est greffé sur des phospholipides par l'intermédiaire d'un espaceur constitué de polyéthy-…”

Section: Resultsunclassified

Agents de contraste pour l’imagerie médicale

Tsapis

2017

Med Sci (Paris)

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Medical imaging techniques such as magnetic resonance imaging (MRI) or ultrasonography are now well rooted into clinical practice. Nevertheless, to further improve the diagnostic of specific pathologies, contrast agents are needed. Materials used to formulate these agents should be carefully selected to interact with the physical stimulus in a way that the collected signal is as intense as possible, according to the imaging technique used. In addition, materials these agents are made of should exhibit no toxicity or the lowest toxicity compared to their medical benefits. We present here the state of the art for contrast agents used in MRI and ultrasonography.

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Ultrasound Contrast Materials in Cardiovascular Medicine: from Perfusion Assessment to Molecular Imaging

Cited by 15 publications

References 61 publications

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Agents de contraste pour l’imagerie médicale

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