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The development of ingenious, non-ionising radiation-based technologies in the field of optical photonics has revolutionised biomedical imaging by superseding the ionising radiation-based technologies such as harmful X-Rays. By implementing novel optical systems, several biomedical imaging methodologies have been enhanced into high-throughput and agile systems. These find use in applications ranging from the visualisation of complex structures inside the biological tissue to detection, identification, and monitoring of fatal disorders. Photoacoustic microscopy (PAM) is one such imaging modality, offering visualisation of micro-macro level structures, owing to the interplay of the optical excitation with differentiation of the structures resting on their intrinsic optical absorption-based acoustic detection. Various PAM based single-wavelength laser systems have shown their applicability for the commonly encountered endogenous biomolecules like nucleic acids, haemoglobin, melanin, collagen, lipids, and many more, by acting as contrast agents for different disorders. In contrast, photonic crystal fibre (PCF) based supercontinuum (SC) lasers provide a broad spectral emission bandwidth, typically ranging from 400 nm to 2400 nm. This range is immensely useful since it covers the absorption features of all the endogenous molecules mentioned above. With this broadbandwidth, a PCFSC laserbased PAM system should enable the use of a single laser system for targeting all the endogenous molecules’ specific absorption features that fall within the emission spectrum of the SC laser. Nevertheless, the limited pulse energy density (PED) intrinsic to the PCF-based SC laser sets a major drawback to its practical implementation for multispectral PAM (MS-PAM) of various endogenous molecules. In this thesis, we present a novel way to tailor the SC lasers in combination with a linear variable filter, enabling the utilisation of MS-PAM for specific endogenous molecules in the wavelength region from 1500 nm to 1850 nm - notably lipids and glucose. The presented SC lasers are built from standard telecom range optical components, which can be spliced using an arc/fusion splicer, thereby making them low-cost, compact and flexible optical systems based entirely on fibre components. The ‘G2_SC’ laser detailed in the latter part of this thesis, feature PED and pulse repetition rate (PRR) of over three times higher than any SC laser reported for MS-PAM applications so far. Moreover, the high-PED of the SC lasers enable high-resolution MS-PAM studies when used in combination with narrow bandwidth filters, andthehigh-(PRR) facilitates much faster image acquisition rates. To further demonstrate the practicality of the presented SC lasers, we performed MS-PAM of ex vivo adipose tissue, multispectral photoacoustic spectroscopy (MS-PAS) of in vitro glucose solutions as well as MS-PAM of in vivo Xenopus laevis tadpoles. Notably - in the case of lipids - our studies have shown that the presented SC-based MS-PAM system can visualise lipids in both ex vivo tissues and in vivo small animal bodies (with an acquisition time of less than 52 s), allowing for broad applicability in real-time biomedical imaging systems. We are confident that the presented high-PED SC laser system paves a new path towards more compact and low-cost sources for non-invasive, real-time imaging of multiple endogenous biological molecules in both developmental biology of small animal bodies and medical imaging.
|Publisher||Technical University of Denmark|
|Number of pages||131|
|Publication status||Published - 2020|
01/02/2017 → 01/04/2020