Laser ultrasonic imaging of subsurface defects with the linear sampling method.

Laser ultrasonics is a remote nondestructive evaluation technique suitable for real-time monitoring of fabrication processes in semiconductor metrology, advanced manufacturing, and other applications where non-contact, high fidelity measurements are required. Here we investigate laser ultrasonic data processing approaches to reconstruct images of subsurface side drilled holes in aluminum alloy specimens. We demonstrate through simulation that the model-based linear sampling method (LSM) can perform accurate shape reconstruction of single and multiple holes and produce images with well-defined boundaries. We experimentally confirm that LSM produces images that represent the internal geometric features of an object, some of which may be missed by conventional imaging.

Photoacoustic Impulse Response of Lipid-Coated Ultrasound Contrast Agents.

The utility of ultrasound imaging and therapy with microbubbles may be greatly enhanced by determining their impulse-response dynamics as a function of size and composition. Prior methods for microbubble characterization utilizing high-speed cameras, acoustic transducers and laser-based techniques typically scan a limited frequency range. Here, we report on the use of a novel photoacoustic technique to measure the impulse response of single microbubbles. Individual microbubbles are driven with a broadband photoacoustic wave generated by a nanosecond-pulse laser illuminating an optical absorber. The resulting microbubble oscillations were detected by following transmission of a second laser as it passes twice through the microbubble. The system could even resolve oscillations resulting from a single-shot. As a proof-of-concept study, the size-dependent, linear impulse response of lipid-coated microbubbles was characterized using this technique. This unique method of microbubble characterization with exceptional spatiotemporal resolution opens new avenues for capturing and analyzing microbubble system dynamics.

The effect of size range on ultrasound-induced translations in microbubble populations.

Microbubble translations driven by ultrasound-induced radiation forces can be beneficial for applications in ultrasound molecular imaging and drug delivery. Here, the effect of size range in microbubble populations on their translations is investigated experimentally and theoretically. The displacements within five distinct size-isolated microbubble populations are driven by a standard ultrasound-imaging probe at frequencies ranging from 3 to 7 MHz, and measured using the multi-gate spectral Doppler approach. Peak microbubble displacements, reaching up to 10 µm per pulse, are found to describe transient phenomena from the resonant proportion of each bubble population. The overall trend of the statistical behavior of the bubble displacements, quantified by the total number of identified displacements, reveals significant differences between the bubble populations as a function of the transmission frequency. A good agreement is found between the experiments and theory that includes a model parameter fit, which is further supported by separate measurements of individual microbubbles to characterize the viscoelasticity of their stabilizing lipid shell. These findings may help to tune the microbubble size distribution and ultrasound transmission parameters to optimize the radiation-force translations. They also demonstrate a simple technique to characterize the microbubble shell viscosity, the fitted model parameter, from freely floating microbubble populations using a standard ultrasound-imaging probe.

Changes in microbubble dynamics upon adhesion to a solid surface.

The interaction between an acoustically driven microbubble and a surface is of interest for a variety of applications, such as ultrasound imaging and therapy. Prior investigations have mainly focused on acoustic effects of a rigid boundary, where it was generally observed that the wall increases inertia and reduces the microbubble resonance frequency. Here we investigate the response of a lipid-coated microbubble adherent to a rigid wall. Firm adhesion between the microbubble and a glass surface was achieved through either specific (biotin/avidin) or nonspecific (lipid/glass) interactions. Total internal reflection fluorescence microscopy was used to verify conditions leading to either adhesion or non-adhesion of the bubble to a glass or rigid polymer surface. Individual microbubbles were driven acoustically to sub-nanometer-scale radial oscillations using a photoacoustic technique. Remarkably, adherent microbubbles were shown to have a higher resonance frequency than non-adherent microbubbles resting against the wall. Analysis of the resonance curves indicates that adhesion stiffens the bubble by an apparent increase in the shell elasticity term and decrease in the shell viscosity. Based on these results, we conclude that surface adhesion is dominant over acoustic effects for low-amplitude microbubble oscillations.

Photoacoustic technique to measure temperature effects on microbubble viscoelastic properties.

Phospholipid-coated microbubbles are being developed for several biomedical applications, but little is known about the effect of temperature on the viscoelastic properties of the shell. Here, we report on the use of a photoacoustic technique to study the shell properties of individual microbubbles as a function of temperature. The microbubbles were driven into small-amplitude oscillations by ultrasound waves generated from the absorption of an intensity-modulated infrared laser, and these oscillations were detected by forward-light scattering of a second blue laser. The drive laser modulation frequency was swept to determine the resonant response of 2-4 µm radius microbubbles. Lipid shell elasticity and viscosity were determined by modeling the microbubble response as a linear harmonic oscillator. The results from slow heating showed a linear decrease in elasticity and viscosity between 21 and 53 °C and a corresponding increase in the maximum oscillation amplitude. Rapid heating to 38 °C, on the other hand, showed a transient response in the viscoelastic properties, suggesting shell rupture and reformation during microbubble growth and subsequent dissolution. These effects are important for biomedical applications, which require warming of the microbubbles to body temperature.

Single Microbubble Measurements of Lipid Monolayer Viscoelastic Properties for Small-Amplitude Oscillations.

Lipid monolayer rheology plays an important role in a variety of interfacial phenomena, the physics of biological membranes, and the dynamic response of acoustic bubbles and drops. We show here measurements of lipid monolayer elasticity and viscosity for very small strains at megahertz frequency. Individual plasmonic microbubbles of 2-6 µm radius were photothermally activated with a short laser pulse, and the subsequent nanometer-scale radial oscillations during ring-down were monitored by optical scatter. This method provided average dynamic response measurements of single microbubbles. Each microbubble was modeled as an underdamped linear oscillator to determine the damping ratio and eigenfrequency, and thus the lipid monolayer viscosity and elasticity. Our nonisothermal measurement technique revealed viscoelastic trends for different lipid shell compositions. We observed a significant increase in surface elasticity with the lipid acyl chain length for 16 to 20 carbons, and this effect was explained by an intermolecular forces model that accounts for the lipid composition, packing, and hydration. The surface viscosity was found to be equivalent for these lipid shells. We also observed an anomalous decrease in elasticity and an increase in viscosity when increasing the acyl chain length from 20 to 22 carbons. These results illustrate the use of a novel nondestructive optical technique to investigate lipid monolayer rheology in new regimes of frequency and strain, possibly elucidating the phase behavior, as well as how the dynamic response of a microbubble can be tuned by the lipid intermolecular forces.