Surfactant stabilized microbubbles are widely used clinical contrast agents for ultrasound imaging. In this work, the light propagation through a turbid medium in the presence of microbubbles has been investigated. Through a series of experiments, it has been found that the optical attenuation is increased when the microbubbles in a turbid medium are insonified by ultrasound. Such microbubble enhanced optical attenuation is a function of both applied ultrasound pressure and microbubble concentration. To understand the mechanisms involved, a Monte Carlo (MC) model has been developed. Under ultrasound exposure, the sizes of microbubbles vary in space and time, and their dynamics are modeled by the Rayleigh-Plesset equation. By using Mie theory, the spatially and temporally varying optical scattering and scattering efficiency of microbubbles are determined based on the bubble sizes and internal refractive indices. The MC model is shown to effectively describe a medium with rapidly changing optical scattering, and the results are validated against both computational results using an N-layered diffusion equation model and experimental results using a clinical microbubble contrast agent (SonoVue®).
Near-infrared spectroscopy (NIRS) can provide an estimate of the mean oxygen saturation in tissue. This technique is
limited by optical scattering, which reduces the spatial resolution of the measurement, and by absorption, which makes
the measurement insensitive to oxygenation changes in larger deep blood vessels relative to that in the superficial tissue.
Acousto-optic (AO) techniques which combine focused ultrasound (US) with diffuse light have been shown to improve
the spatial resolution as a result of US-modulation of the light signal, however this technique still suffers from low
signal-to-noise when detecting a signal from regions of high optical absorption. Combining an US contrast agent with
this hybrid technique has been proposed to amplify an AO signal. Microbubbles are a clinical contrast agent used in
diagnostic US for their ability to resonate in a sound field: in this work we also make use of their optical scattering
properties (modelled using Mie theory). A perturbation Monte Carlo (pMC) model of light transport in a highly
absorbing blood vessel containing microbubbles surrounded by tissue is used to calculate the AO signal detected on the
top surface of the tissue. An algorithm based on the modified Beer-Lambert law is derived which expresses intravenous
oxygen saturation in terms of an AO signal. This is used to determine the oxygen saturation in the blood vessel from a
dual wavelength microbubble-contrast AO measurement. Applying this algorithm to the simulation data shows that the
venous oxygen saturation is accurately recovered, and this measurement is robust to changes in the oxygenation of the
superficial tissue layer.
Diffuse optical techniques in tissue are insensitive to oxygenation changes inside large blood vessels, due to the high
optical absorption relative to the surrounding tissue. To overcome this a hybrid technique of diffuse light modulated by
focused ultrasound (US) was used to detect an acousto-optic (AO) signal from a large (1 cm diameter) blood-filled tube
surrounded by a turbid medium. An injection of microbubbles, a contrast agent used in clinical diagnostic US, amplified
this AO signal to an experimentally detectable level. The blood was diluted to vary its optical absorption, and a resulting
change in the magnitude of the AO signal was observed. A mechanism by which microbubbles can enhance USmodulation
of light is proposed by deriving a 2nd order approximation to the Rayleigh-Plesset equation of motion for a
bubble in an US field. A Monte Carlo (MC) model of a deep blood vessel geometry has also been developed: this takes
into account the optical scattering from oscillating microbubbles in the blood, which is expected to vary spatially and
temporally. Results of the MC model show that the US-modulated light signal is more sensitive to oxygenation changes
within the blood vessel than a diffuse optical signal. Experimental results show a significant enhancement of the USmodulated
optical signal when microbubbles were introduced.
Acousto-optic (AO) signals can be very weak and the aim of this work was to investigate their amplification using
microbubbles. The acoustic pressure radiated by the microbubbles produces refractive index changes in the surrounding
medium, and this is proposed as an additional mechanism which modulates the phase of photons. The analytical form of
this additional modulation is derived based on the Rayleigh-Plesset equation, which describes microbubble oscillations,
in the case where the microbubble oscillations are linear under low applied ultrasound pressure. We show that
microbubbles can increase the modulation depth of the AO signal using Monte Carlo simulations. The increase in
modulation depth is dependent on the applied ultrasound frequency and the resonance frequency of the microbubbles.
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