Physical Principles of Microbubbles for Ultrasound Imaging and Therapy

Stride, Eleanor

doi:10.1159/000203122

Cited by 92 publications

(104 citation statements)

References 193 publications

(105 reference statements)

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“…Due to their compressible core, they can cavitate in an ultrasonic field. Cavitation is the alternating shrinking and expanding of the microbubbles, according to the pressure phases of the ultrasound wave [6]. Microbubbles were originally developed as contrast agents for ultrasound imaging.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound and microbubble mediated drug delivery: Acoustic pressure as determinant for uptake via membrane pores or endocytosis

Cock

Zagato

Braeckmans

et al. 2015

Journal of Controlled Release

221

247

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Although promising results are achieved in ultrasound mediated drug delivery, its underlying biophysical mechanisms remain to be elucidated. Pore formation as well as endocytosis has been reported during ultrasound application. Due to the plethora of ultrasound settings used in literature, it is extremely difficult to draw conclusions on which mechanism is actually involved. To our knowledge, we are the first to show that acoustic pressure influences which route of drug uptake is addressed, by inducing different microbubble-cell interactions. To investigate this, FITC-dextrans were used as model drugs and their uptake was analyzed by flow cytometry. In fluorescence intensity plots, two subpopulations arose in cells with FITCdextran uptake after ultrasound application, corresponding to cells having either low or high uptake. Following separation of the subpopulations by FACS sorting, confocal images indicated that the low uptake population showed endocytic uptake. The high uptake population represented uptake via pores. Moreover, the distribution of the subpopulations shifted to the high uptake population with increasing acoustic pressure. Real-time confocal recordings during ultrasound revealed that membrane deformation by microbubbles may be the trigger for endocytosis via mechanostimulation of the cytoskeleton. Pore formation was shown to be caused by microbubbles propelled towards the cell. These results provide a better insight in the role of acoustic pressure in microbubble-cell interactions and the possible consequences for drug uptake. In addition, it pinpoints the need of a more rational, microbubble behavior based choice of acoustic parameters in ultrasound mediated drug delivery experiments.

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Section: Introductionmentioning

confidence: 99%

Ultrasound and microbubble mediated drug delivery: Acoustic pressure as determinant for uptake via membrane pores or endocytosis

Cock

Zagato

Braeckmans

et al. 2015

Journal of Controlled Release

221

247

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show abstract

“…3 The shell also affects the nonlinear response of microbubbles, a key property of UCAs that is often exploited in diagnostic imaging modes for enhanced discrimination between the contrast agent and surrounding tissue. 4 In addition to traditional diagnostic ultrasound imaging, there has been recent interest in advancing the applications of microbubbles for molecular imaging and therapeutic applications. These applications exploit the nonlinear response for selective detection of microbubbles in a given volume for diagnosis and specific targeting of disease.…”

Section: Introductionmentioning

confidence: 99%

“…4 ELIP formulations include a small amount of cholesterol to increase membrane rigidity and are echogenic due to the presence of air, which is entrapped and stabilized by the lipid during the rehydration process. 19 The exact location of the entrapped air pockets, morphology of the encapsulation, and amount of air in each carrier has not been fully ascertained.…”

Section: Introductionmentioning

confidence: 99%

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-highspeed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 Â 10 À8 to 2.5 Â 10 À9 kg/s, was observed with increasing dilatation rate, from 0.5 Â 10 6 to 1 Â 10 7 s À1 . This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [j s ¼ (2.1 6 1.0) Â 10 À8 kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

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“…To evaluate the stable cavitation dose (SCD) representing the extent of MB's nonlinear oscillation and the inertial cavitation dose (ICD) for MB fragmentation or destruction 14 , the amplitudes of harmonics, ultraharmonics and the broadband signals in 1-5 MHz were used. This frequency range was selected in order to avoid the influence of fundamental frequency while retain the information of PCD signals.…”

Section: Pcd Data Analysismentioning

confidence: 99%