Non Linear Ultrasound Doppler and the Detection of Targeted Contrast Agents
Creators: name: Mahue, Veronique Catherine
Publisher: name: Imperial College London
Year: 2011

description: One of the main challenges in molecular imaging with targeted contrast agents is the detection and discrimination of attached agents from the rest of the signals originating from freely flowing agents and tissue. The aim of this thesis was to develop methods for the detection of targeted microbubbles. One approach consisted of investigating the use of nonlinear Doppler for this purpose. Nonlinear Doppler enables the differentiation of moving from non-moving and linear from nonlinear scattering. Targeted microbubbles are static and nonlinear scatterers and they should be detected using this technique. A novel nonlinear Doppler technique: Pulse subtraction Doppler, was developed and compared to pulse inversion Doppler. It is shown that both techniques lead to similar Doppler spectra and depending on the medical applications and the equipment limitations, both techniques have benefits. This served as a starting point for the derivation of a generalised nonlinear Doppler technique, based on combined linear pulse pair sequences and tested in a simulation study. The response from a single microbubble was simulated for different pulse combinations and the pulse sequences were compared with regards to criteria specific to imaging requirements. It was shown that depending on initially set criteria, such as transmitted energy, mechanical index or scanner characteristics, certain pulse combinations offer alternatives to the current imaging modalities and allow to take into account specific constrains due to the targeted application/equipment. Furthermore, the proposed approach is directly applicable in a strict non linear imaging approach, without Doppler processing. An in vitro phantom was designed in order to assess pulse subtraction Doppler for the detection and discrimination of static nonlinear microbubbles in the presence of free flowing ones. It was shown that pulse subtraction Doppler enables such discrimination and the practicability for in vivo situations is discussed. The pulse subtraction Doppler sequences were also tested on a phantom containing magnetic bubbles. It was shown that the magnetic bubbles can be immobilised through a magnetic field to a specific region of interest under flow conditions. The bubbles also showed to be acoustically detectable and to scatter linearly at diagnostic driving pressures. Preliminary work regarding experimental biotinylated microbubbles and their attachment to streptavidin coated surfaces is also presented. Due to their proximity to a wall, researchers have found that targeted microbubbles exhibit different acoustic signatures compared to free ones and this knowledge can improve their detection techniques. The behaviour of microbubbles against a membrane of varying stiffness was also studied through high speed camera observations. It was found both experimentally and by comparison to theoretical modelling that within the stiffness range of human blood vessels the change in acoustical behaviour of microbubbles is negligible. This thesis has taken two complementary research approaches which have shown to constitute advancements for the detection and discrimination of targeted microbubbles.