Advancing Upconversion Emissions for Biomedical Imaging
Abstract: During the past decade, upconverting nanoparticles (UCNPs) doped with rare earth ions have become an important class of fluorescence contrast agents for molecular imaging, due to their unique properties. Their property of anti-Stokes luminescence, with both the excitation and emission wavelengths close to the optimal for biomedical imaging, has been extensively explored in various biomedical applications. The work described in this thesis is mainly concerned with the investigation of other unique properties of UCNPs, including nonlinearity and saturation, to improve fluorescence diffuse imaging and tomography. The aim of this work was also to develop a suitable method of characterizing the power-density-dependent quantum yield of UCNPs, and to optimize the excitation scheme in order to facilitate their use in deep tissues. Upconversion emission has a nonlinear dependence on the excitation intensity. This nonlinearity was exploited to improve the image reconstruction quality in fluorescence diffuse optical tomography, by increasing the orthogonal information density through simultaneous multibeam excitation. It is also demonstrated that the use of nonlinear UCNPs as contrast agents in fluorescence tomography can breach the current limit on spatial resolution encountered when using linear fluorophores. UCNPs can emit multiple emission bands with large differences in tissue attenuation under excitation of near-infrared light. Such multispectral information was used to create a regularization map to guide fluorescence diffuse optical tomography, which yielded significantly better axial resolution in the reconstructed images than using standard Tikhonov regularization. The quantum yield of upconversion emission increases with excitation intensity and gradually reaches a plateau. In this work, an initial model was developed to describe the quantum yield of two-photon upconversion emission as a function of the excitation intensity, based on rate equation analysis. A balancing power density was identified, which characterizes the excitation-intensity dependence of the quantum yield. At such a power density, the quantum yield reaches half the maximum attainable value, occurring at very high excitation intensities when UCNPs are saturated. Pulsed excitation is proposed as a superior mode of excitation to continuous wave excitation, due to the potential of achieving higher intrinsic quantum yields from UNCPs without increasing the average excitation power. This will fundamentally increase the applicability of UCNPs in deep tissues.
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