S.M. van der Meer

Changes in microbubble dynamics near a boundary revealed by combined optical micromanipulation and high-speed imaging

The authors report optical observations of the change in the dynamics of one and the same ultrasound contrast agent microbubble due to the influence of interfaces and neighboring bubbles. The bubble is excited by a 2.25MHz ultrasound burst and its oscillations are recorded with an ultrahigh-speed camera at 15 million frames per second. The position of an individual bubble relative to a rigid wall or second bubble is precisely controlled using optical tweezers based on Laguerre-Gaussian laser beams [P. Prentice et al., Opt. Express 12, 593 (2004); V. Garbin et al., Jpn. J. Appl. Phys. 44, 5773 (2005)]. This allows for repeated experiments on the very same bubble and for a quantitative comparison of the effect of boundaries on bubble behavior.

Microbubble surface modes [ultrasound contrast agents]

We have investigated surface vibrations generated by ultrasound excitation of individual unencapsulated micron-sized bubbles. In addition, we present surface modes (n=2 and 3) observed for phospholipid-coated ultrasound contrast agents excited through excitation of radial modes at frequencies between 1 and 4 MHz. Even higher modes of vibration (up to mode 5) are observed for coated microbubbles at insonation frequencies of 10 and 19 MHz. The potential relevance of surface modes for medical ultrasound is discussed, including the possible implications for current theoretical models of ultrasound contrast agents.

The resonance frequency of SonoVue/spl trade/ as observed by high-speed optical imaging

The resonance frequencies of individual SonoVue/spl trade/ contrast agent bubbles were measured optically by recording the radius-time curves of a single microbubble at 24 different frequencies. For these experiments, the Brandaris 128 fast framing camera was operated in a special segmented mode. The resonance frequencies found for SonoVue/spl trade/ microbubbles are in good agreement with the modified Herring model for coated bubbles indicating that the shell only slightly affects the resonance frequency of this class of contrast bubbles.

1B-5 Surface Modes of Ultrasound Contrast Agent Microbubbles

We study non-spherical oscillations (surface modes) of the coated microbubbles used in ultrasound contrast agents. We show that an acoustic pressure of 100 kPa, at a frequency of 1.7 MHz, is sufficient to excite surface modes for radii between 2 and 4 mum. Surface modes develop as a parametric instability. We derive their evolution equation accounting for the effect of the shell viscoelasticity. We identify a critical radius (1 to 3 mum, depending on the mode number) below which no surface mode can occur

1F-2 Optical Trapping of Ultrasound Contrast Agent Microbubbles: Study of the Bubble-Wall and Bubble-Bubble Interaction in Ultrasound

Here we present optical tweezers as a micromanipulation tool for the study of ultrasound contrast agent (UCA) microbubbles. Optical trapping and the resulting manipulation of individual and multiple microbubbles enables the study of their dynamics with controlled boundary conditions. The bubble response to ultrasound is recorded optically using the ultra high-speed Brandaris 128 camera. In our experiments, the amplitude of bubble oscillations was found to be strongly influenced by the vicinity of the sample chamber wall. Experiments with two trapped bubbles also showed a considerable influence of the neighboring bubble on the amplitude of oscillations of the other one

P5B-4 Optimization of Chirp Reversal for Ultrasound Contrast Imaging

Chirp reversal consists of transmitting first a chirp with upsweep frequencies (UPF) then a second chirp with downsweep frequencies (DNF). We have shown that contrast bubbles react differently to these chirps allowing the use of chirp reversal for ultrasound contrast imaging. The aim of the current study is to explore how chirp reversal can be optimized in terms of transmit frequency, bubble size, acoustic pressure and frequency bandwidth. Simulations were carried out to determine ultrasound parameters that provide largest differences in bubbles response to UPF and DNF chirps. Scattered pressures were calculated using a modified Rayleigh-Plesset equation. To evaluate the performance of chirp reversal for bubble detection, the echo from an UPF chirp was correlated to the time reversed echo from a DNF chirp for each scanning parameter. Simulations and optical measurements allow for an optimization of chirp reversal and demonstrate a potential application for contrast imaging when appropriate scanning parameters are selected.

2C-4 Chirp Reversal Ultrasound Contrast Imaging

We present a new contrast imaging approach based on chirps named chirp reversal contrast imaging. The technique consists of transmitting a first excitation signal being a chirp of increasing frequency with time (the so-called upsweep) and a second excitation signal, the downsweep, being a replica of the first signal, but time reversed with a sweep of decreasing frequency with time. Simulations and optical observations were carried out to explore the potential of the chirp reversal approach in detecting microbubbles. Simulations using a Rayleigh-Plesset equation were performed considering various microbubbles excited with chirps at 1.7 MHz center frequency and 50% bandwidth. Optical observations with the Brandaris camera were carried out using BR14 bubbles of radii from 1 mum to 5 mum. Chirps with center frequencies of 1.7 MHz and 50% bandwidth were transmitted with peak negative pressures ranging from 70 kPa to 200 kPa. Simulations showed that for larger bubbles (>2 mum), significant differences occur between upsweep chirp response and down sweep response at 1.7 MHz transmit frequency. Optical observations confirmed these results. From the optical radius-time curves, the larger bubbles showed different dynamics when upsweep or downsweep frequencies were used in transmission. Upsweep excitation chirps produce highly damped responses with large amplitude excursions whereas the response to downsweep chirps showed a pronounced resonance behavior with smaller amplitudes. Smaller bubbles (<2 mum) appear to be less sensitive to frequency sweep at 1.7 MHz transmit frequency. However, driven at a higher center frequency, smaller bubbles tend to be more sensitive. Experimental and theoretical data confirm that chirp reversal is feasible and can be used to detect contrast microbubbles and to improve the contrast to tissue ratio