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Ultrasound-modulated Microbubbles as a Contrast Agent for Optical Spectroscopy in Biomedical Applications

Honeysett, JEP; (2013) Ultrasound-modulated Microbubbles as a Contrast Agent for Optical Spectroscopy in Biomedical Applications. Doctoral thesis (PhD), UCL (University College London). Green open access

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Abstract

Microbubbles, which are currently used as contrast agents for diagnostic ultrasound (US) imaging, are proposed in this thesis as an optical scattering contrast agent for US-modulated light. Sometimes known as acousto-optic (AO) imaging, this is a hybrid technique which combines measurement of di↵use light in a turbid medium (such as biological tissue) with US, which modulates the properties of the tissue, specifically density, optical scattering and optical absorption. Hence the light field passing through the insonified region will also be modulated. The modulated optical signal provides greater spatial resolution than is usually achieved with di↵use light, however this signal is often very small compared with the background of unmodulated light. This work investigates the use of microbubbles to amplify the US-modulation of light within the US focal region, by acting as an optical scattering contrast agent. The approach combines analytical modelling of microbubble behaviour under US using solutions of a Rayleigh-Plesset type equation with Monte Carlo (MC) modelling of light transport. Simulations of 780 nm wavelength light reflected from a large (10 mm diameter) blood vessel below a 10 mm depth of tissue show that a measurable change in optical attenuation is induced by insonifying microbubbles within the blood vessel. To model this complex geometry an approach based on perturbation Monte Carlo (pMC) is used, which improves the computational efficiency by several orders of magnitude. This microbubble-enhanced optical attenuation change (MOA) is also measured experimentally from an intralipid phantom containing microbubbles, which are insonified by US at clinically relevant pressures, using a 780 nm laser source and photon counter. The magnitude of this MOA signal is shown to increase with applied US pressure and also with microbubble concentration. Finally, a dual-wavlength optical measurement of MOA from a blood vessel is simulated using pMC. An analytical algorithm based on the Beer-Lambert law is derived which can accurately infer the oxygen saturation of the blood vessel from this MOA measurement for blood vessel up to 20 mm below the tissue surface. This algorithm is accurate even when the oxygenation of the surrounding tissue varies. This suggests that this technique could be used to measure venous oxygen saturation in superficial blood vessels such as the jugular vein or pulmonary artery, particularly in young children.

Type: Thesis (Doctoral)
Qualification: PhD
Title: Ultrasound-modulated Microbubbles as a Contrast Agent for Optical Spectroscopy in Biomedical Applications
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from ethesis.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1401081
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