Stahl, T; (2017) Characterisation of Contrast Agents for Photoacoustic Imaging. Doctoral thesis , UCL (University College London).

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Abstract

Photoacoustic imaging is a promising imaging modality which combines both excellent spatial resolution with high contrast and specificity. This makes it well suited to clinical and pre-clinical studies of the physiological changes which accompany conditions such as cancer and cardiovascular disease. In order to fully realize the potential of this technique, new contrast agents with the ability to generate strong PA signals upon excitation with light in the near infrared, good stability and biocompatibility, are required. Previously, numerous absorbing materials have been proposed for this purpose. Their potential to generate PA contrast is frequently evaluated using purely optical methods (e.g. absorption spectroscopy). This practice however fails to account for relevant thermodynamic properties involved in the PA signal generation process, namely the thermalisation efficiency (Et) and the Grüneisen coefficient (Г). To address this, a PVDF-based PA spectroscopic set-up was designed and methods developed which allowed the determination of the absorption coefficient (μa), Et, Г, PA amplitude and μa spectra as well as enabling analysing the photostability. In order to identify promising contrast agents for molecular PA imaging an array of nanoparticles was synthesised and together with various commercial available nanoparticles and organic dyes their ability to generate strong PA signals was evaluated using the PA spectroscope. π-conjugated polymeric nanoparticles demonstrated the ability to generate strong PA signals upon excitation and were therefore analysed in preliminary in vitro targeting experiments. In order to show the ability of the π-conjugated polymeric nanoparticles to generate strong PA signals under realistic conditions, in vivo animal experiments were carried out. The in vivo experiments demonstrate that at 800 nm the novel π-conjugated polymeric nanoparticle based on the polymer INDT-BT can be detected in the presence of the endogenous chromophores such as haemoglobin and water, allowing to unambiguously image the presence of the nanoparticles.

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