title: Establishing a high-sensitivity photoacoustic tomography system for applications in life sciences
creator: Czuchnowski, Jakub
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-570
subject: 570 Life sciences
description: Understanding biology across various spatial scales requires appropriate tools that allow the collection and analysis of information about specific events throughout the organism of interest. Imaging techniques are one of the most powerful tools of modern biology enabling direct visualisation of structures and processes with high spatial resolution and often in real time. Especially potent imaging modalities were developed based on light microscopy that allow high resolution imaging in the cellular and subcellular regimes. Unfortunately, these techniques are not suitable for imaging in highly scattering and thick samples such as mammalian tissues. While those can be imaged by biomedical imaging techniques such as MRI or CT, they typically achieve much lower lowered spatial and temporal resolution as well as are incompatible with the large toolkit of molecular probes and approaches used in life sciences (e.g. fluorescent proteins).    Here, emerging technologies based on photoacoustic imaging (where light is used to excite acoustic waves inside the tissue) enable bridging the biomedical and biological techniques by combining light based excitation (that is compatible with the optical toolkit of life sciences) with deep penetration capabilities characteristic for the biomedical regime. Several techniques of photoacoustic imaging were developed with photoacoustic tomography emerging as a particularly interesting modality for large-volume, high-quality imaging in mammalian tissues, due to it's ability to simultaneously record information from the whole volume of interest. In particular, there is a rising interest in developing all-optical photoacoustic approaches which use light both for exciting and detecting the acoustic waves. These bring promise of simplification and miniaturisation of the detector elements which would allow for easier animal handling and enable combination with other light based modalities such as multiphoton microscopy.    The aim of this thesis was to establish a high-performance state-of-the-art all-optical photoacoustic system based on a Fabry-P\'erot pressure sensor that could be used in life sciences for imaging applications in mouse biology. In particular, I explored possible improvements in speed and sensitivity with the long-term goal to enable whole-brain calcium based neuroimaging in mice. In this thesis, I describe my work towards the realization of this system including the detailed discussion of the system design and operating principles. I show preliminary imaging experiments in fish and mice to validate the capabilities of our photoacoustic tomography setup to perform high resolution \textit{in vivo} imaging.    The main part of the thesis is then concerned with the description of various approaches for increasing photoacoustic tomography sensitivity, including the use of adaptive optics for enhanced cavity coupling, passive photodiode amplification as well as deep learning based denoising. Furthermore, a full theoretical framework is presented for explaining the effects of interactions between optical aberrations and Fabry-P\'erot cavity modes, which is then extended to explain fundamental optical processes in adaptive optics. Moreover, two frameworks are described for increasing the volume rate of Fabry-P\'erot based systems including optimising the scanning trajectory as well as using optical multiplexing for parallel readout from the sensor. Finally, further directions of work are discussed including tackling the effects of skull induced acoustic aberrations on the image resolution and the choice of possible candidates for photoacoustic calcium sensors.
date: 2022
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/30150/1/JakubCzuchnowski_PhD_Thesis.pdf
identifier: DOI:10.11588/heidok.00030150
identifier: urn:nbn:de:bsz:16-heidok-301500
identifier:   Czuchnowski, Jakub  (2022) Establishing a high-sensitivity photoacoustic tomography system for applications in life sciences.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/30150/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng