Developing opto-acoustic microscopy instruments for biomedical imaging applications

Opto-acoustic Microscopy is an emerging technique for cross-sectional imaging that provides structural and functional volumetric information with micrometer resolution. This allows for non-invasive detection of endogenous contrast agents and chromophores without using ionizing radiation. The objective of this thesis is to investigate the potential of opto-acoustic microscopy combined with optical coherence tomography in developing advanced diagnostic tools for biomedical applications, in particular for cancer diagnosis. To achieve this objective, the thesis focuses on in-vivo multi-spectral optoacoustic microscopy imaging of multiple endogenous contrast agents in Xenopus laevis. The study used a high-resolution opto-acoustic microscopy instrument capable of multi-pectral imaging covering two octaves of the spectrum, and a novel technique to distinguish between different chromophores in the sample. An optical coherence tomography instrument was integrated in the opto-acoustic microscopy system to guide imaging and provide reliable structural information. Additionally, visible light optical coherence tomography system was developed as an ultra-high resolution alternative. Prior to this study, mapping of lipids in Xenopus laevis was achieved using an in-house all-fibre supercontinuum optical source developed in DTU, Denmark operating in the extended near-infrared region. Both opto-acoustic microscopy and optical coherence tomography instruments are capable of acquiring cross-sectional and volumetric images in real-time. Finally, a high-resolution opto-acoustic microscopy set-up to explore the impact of picosecond pulse duration excitation on the axial resolution of the imaging system. The study compared a picosecond pulse duration laser-based optoacoustic microscopy instrument to a nanosecond laser-based one in terms of axial resolution and obtained unprecedented in-vivo images of the brain in Xenopus laevis tadpoles.