3D Photoacoustic Molecular Imaging

• Author / Creator

  Chee, Ryan

• Molecular imaging is allowing researchers to make ground breaking strides in science and medicine by imaging molecular processes in vivo. Applications include detecting disease biomarkers, improving drug efficacy, studying biochemistry, and understanding disease mechanisms of action. Photoacoustic (PA) imaging is a promising non-invasive imaging technique that uses pulse laser excitation to induce PA signals. PA imaging has promising potential as a molecular imaging technique, but it has yet to be fully realized. In comparison to other comparable molecular imaging methods like fluorescence imaging, PA imaging has significantly higher resolutions and faster imaging rates at a 1-5 cm imaging depth. This makes PA imaging potentially ideal for small animal studies which are the backbone of biomedical discovery and innovation. With further advances into 3D PA imaging technology and molecular PA contrast agents, PA molecular imaging could become an essential molecular imaging technique in various fields of scientific research.
  This thesis aims to further 3D PA molecular imaging via a multi-dimensional approach by integrating work on transducers, molecular contrast agents, and PA applications. We start with the development of a promising capacitive micromachined ultrasonic transducer (CMUT) known as a top-orthogonal-to-bottom-electrode (TOBE) CMUT, which was developed to improve the feasibility of acquiring and transferring signals from large 3D imaging arrays. We characterize and demonstrate the potential of such arrays for 3D PA imaging. We also demonstrate that these TOBE CMUTs can potentially acquire 3D PA images orders of magnitude faster than traditional large 3D imaging arrays using a novel design specific technique known as modulation encoding. We then developed interlaced multifrequency CMUTs to increase imaging sensitivity to molecular PA contrast agents. Interlaced multifrequency CMUTs have a broader bandwidth, allowing improved detection of diffuse contrast agents in comparison to high-frequency clinical transducers all while maintaining the ability to image fine structures. This was followed by our work on background signal suppression using novel photoswitchable PA molecular contrast agents, sGPC2 and sGPC3. These photoswitchable PA contrast agents can be tagged to molecules of interest for molecular imaging and can reduce background signals by switching between two absorption states. Furthermore, we introduce a technique to simultaneously image and distinguish multiple photoswitchable contrast agents for multiplexed molecular imaging. Multiplexed molecular imaging is essential for imaging real molecular processes that have multiple targets of interest. Finally, we apply photoacoustic imaging to the quantification of tumour volumes to help study the role of p110β in tumour angiogenesis. We compare the accuracy of the PA measurements by comparing it with measured values obtained via staining histology.

• Subjects / Keywords

  • Molecular Imaging
  • CMUTs
  • Photoacoustic Imaging

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R35M62P6K

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.