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.