Optically Modulated Fluorescence-Informed Photoacoustic Imaging

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Islam, Md Shariful
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Abstract
Advanced imaging technology is crucial for detecting early anomalies in deep tissue. While current medical imaging techniques show great potential, there is still a persistent need for improvements in sensitivity, resolution, penetration depth, and cost-effectiveness. Photoacoustic imaging combines optical excitation with acoustic detection to enhance tissue penetration depth and functional imaging capabilities. However, despite these advantages, photoacoustic imaging still suffers from poor signal-to-noise ratio and interference from endogenous chromophores in the background. Dual-laser background suppression techniques have the potential to enhance imaging sensitivity, especially in high-background noise situations. Synchronously amplified fluorescence image recovery (SAFIRe) reduces background interference in fluorescence imaging by manipulating ground-state and intermediate-state populations of contrast agents through pump and probe excitations. The main focus of this thesis is to combine the benefits of SAFIRe with photoacoustic imaging using the same pump-probe technique. Photoacoustic imaging provides signals from deep tissue, and SAFIRe removes the background from that signal. To achieve this objective, optically modulatable contrast agents and their nanoparticles, such as Rose Bengal (RB) and Eosin Y (EY), were used to produce synchronously amplified photoacoustic image recovery (SAPhIRe) signals from tissue-mimicking phantoms and dead rat muscles. This thesis explores the possible uses of SAPhIRe in temporal unmixing, a technique that allows for the separate detection of multiple contrast agents with the same absorption window simultaneously by using their unique triplet-state lifetimes. The study demonstrated the unmixing of RB and EY signals using both fluorescence and photoacoustic techniques. This was achieved by adjusting the pump-probe delay to distinguish their distinct triplet-state lifetimes. The fitting coefficients of triplet-state lifetimes were used to reconstruct images within tissue-mimicking phantoms. Prior to photoacoustic imaging, fluorescence was used for modulation screening. In addition, this work investigates the photophysical properties of three near-infrared (NIR) thiacarbocyanine dyes. Various optical modulation techniques, such as single and dual laser modulation, were conducted to explore their modulation depth, optical properties, and dark-state lifetimes. The results revealed that 3,3'-Diethylthiatricarbocyanine iodide (DTTCI) and 3,3'-Diethylthiacarbocyanine (DTCI) iodide have long dark states and are optically modulatable. Among the two, DTTCI appears to be an ideal candidate for SAPhIRe as it absorbs around 760 nm.
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2023-12-10
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Dissertation
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