Ultrasound-mediated destruction of contrast microbubbles used for medical imaging and drug delivery

Chatterjee, Dhiman; Jain, Pankaj; Sarkar, Kausik

doi:10.1063/1.2011468

Cited by 52 publications

(31 citation statements)

References 44 publications

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“…In order to estimate the size distribution and concentration of the microbubbles, a 30 µl sample of 10x diluted solution was placed on a microscope slide, which had a chamber of fixed volume, and imaged using bright-field microscopy (Eclipse Ti, Nikon Instruments Inc., Melville, NY,USA) [52]. For small amplitude oscillations [53], the resonant frequency, ω r , of an encapsulated microbubble that incorporates both the affects of stiffness and viscous damping of the shell [37] is given by…”

Section: A Microbubble Manufacture and Characterisationmentioning

confidence: 99%

Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation

McLaughlan

Ingram

Smith

et al. 2013

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

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Abstract-The therapeutic use of microbubbles for targeted drug or gene delivery is a highly active area of research. Phospholipid-encapsulated microbubbles typically have a polydisperse size distribution over the 1-10 µm range and can be functionalised for molecular targeting as well as loaded with drug-carrying liposomes. Sonoporation through the generation of shear stress on the cell membrane by microbubble oscillations is one mechanism that results in pore formation in the cell membrane and can improve drug delivery. A microbubble oscillating at its resonant frequency would generate maximum shear stress on a membrane. However, due to the polydisperse nature of phospholipid microbubbles, a range of resonant frequencies would exist in a single population. In this study, the use of linear chirp excitations was compared with equivalent duration and acoustic pressure tone excitations when measuring the sonoporation efficiency of targeted-microbubbles on human colorectal cancer cells. A 3-7 MHz chirp had the greatest sonoporation efficiency of 26.9 ±5.6 %, compared with 16.4 ±1.1 % for the 1.32-3.08 MHz chirp. The equivalent 2.2 and 5 MHz tone excitations have efficiencies of 12.8 ±2.1 % and 15.6 ±1.1 %, respectively, which were all above the efficiency of 4.1 ±3.1 % from the control exposure.

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Section: A Microbubble Manufacture and Characterisationmentioning

confidence: 99%

Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation

McLaughlan

Ingram

Smith

et al. 2013

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

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“…However, accurate pressure measurement using shift in resonance required producing more uniform and smaller (<10 lm) microbubbles. Later workers [26][27][28] tried to improve upon this idea; however, rapid dissolution of free air bubbles-a micron radius air bubble dissolves in 20 ms [29][30][31] -prevented its practical implementation. Since the development of stable encapsulated ultrasound contrast microbubbles in the 1990s, they are again being considered for pressure estimation.…”

Section: Introductionmentioning

confidence: 99%

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure

Katiyar

Sarkar

Forsberg

2011

The Journal of the Acoustical Society of America

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Variation of subharmonic response from contrast microbubbles with ambient pressure is numerically investigated for non-invasive monitoring of organ-level blood pressure. Previously, several contrast microbubbles both in vitro and in vivo registered approximately linear (5-15 dB) subharmonic response reduction with 188 mm Hg change in ambient pressure. In contrast, simulated subharmonic response from a single microbubble is seen here to either increase or decrease with ambient pressure. This is shown using the code BUBBLESIM for encapsulated microbubbles, and then the underlying dynamics is investigated using a free bubble model. The ratio of the excitation frequency to the natural frequency of the bubble is the determining parameter-increasing ambient pressure increases natural frequency thereby changing this ratio. For frequency ratio below a lower critical value, increasing ambient pressure monotonically decreases subharmonic response. Above an upper critical value of the same ratio, increasing ambient pressure increases subharmonic response; in between, the subharmonic variation is non-monotonic. The precise values of frequency ratio for these three different trends depend on bubble radius and excitation amplitude. The modeled increase or decrease of subharmonic with ambient pressure, when one happens, is approximately linear only for certain range of excitation levels. Possible reasons for discrepancies between model and previous experiments are discussed.

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“…Above a critical excitation level, contrast microbubbles are destroyed (Ammi et al, 2006;Chatterjee et al, 2005a;Chomas et al, 2001). Determining the threshold for subharmonic generation is crucial for nondestructive subharmonic applications.…”

Section: Introductionmentioning

confidence: 99%

Excitation threshold for subharmonic generation from contrast microbubbles

Katiyar

Sarkar²

2011

The Journal of the Acoustical Society of America

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Six models of contrast microbubbles are investigated to determine the excitation threshold for subharmonic generation. The models are applied to a commercial contrast agent; its characteristic parameters according to each model are determined using experimentally measured ultrasound attenuation. In contrast to the classical perturbative result, the minimum threshold for subharmonic generation is not always predicted at excitation with twice the resonance frequency; instead it occurs over a range of frequencies from resonance to twice the resonance frequency. The quantitative variation of the threshold with frequency depends on the model and the bubble radius. All models are transformed into a common interfacial rheological form, where the encapsulation is represented by two radius dependent surface properties-effective surface tension and surface dilatational viscosity. Variation of the effective surface tension with radius, specifically having an upper limit (resulting from strain softening or rupture of the encapsulation during expansion), plays a critical role. Without the upper limit, the predicted threshold is extremely large, especially near the resonance frequency. Having a lower limit on surface tension (e.g., zero surface tension in the buckled state) increases the threshold value at twice the resonance frequency, in some cases shifting the minimum threshold toward resonance.

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Ultrasound-mediated destruction of contrast microbubbles used for medical imaging and drug delivery

Cited by 52 publications

References 44 publications

Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation

Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure

Excitation threshold for subharmonic generation from contrast microbubbles

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