An Investigation Into Fundamental Principles And Systems Of Time-domain Diffuse Fluorescence Tomography

Near-infrared Fluorescent Diffuse Optical Tomography (FDOT) is emerging as a promising tool for small animal imaging. The modality, with the aid of specific fluorescent probes, aims at in vivo visualizing interior cellular and molecular events from fluorescence signals measured on boundary of an intact tissue. FDOT enables both three-dimensional localization of the targeted areas and quantization of the local concentration of the fluorochromes. The time domain technique offers the potential advantages of directly extracting the lifetime information through temporally resolving the fluorescence responses to a pulsed excitation, and has additionally the favorite performances of simultaneously recovering fluorescent yield and lifetime distributions, as well as resolving multiple components.This thesis presents the methodology of time-domain FDOT for slab and circular geometries that are commonly used in practice, involving image reconstruction algorithm, numerical simulations, instrumentation of a multi-channel time-resolved imaging system, and experimental validations. The algorithm is based on a linear generalized pulse spectrum technique that employs the analytical solution to the Laplace-transformed time-domain photon diffusion equation to construct a Born normalized inverse model, which can overcome the impact of the instrumental response function and therefore eliminate the requirement for calibrating the time-origins and the coupling factors of the system. The resultant linear inversions are solved using an algebraic reconstruction technique. A pair of real domain transform-factors is introduced to separate the fluorescent yield and lifetime images.Despite the wide adoption of a CCD camera to continuous-wave FDOT, a fiber-based instrumentation is attractive in time-domain FDOT regime since it can make full use of well-established ultra-high sensitive and ps time-resolved detection techniques, such as a time-correlated single photon counting (TCSPC) technique that have been widely used in time-domain diffuse optical tomography with a great success. Based on the proposed multi-channel TCSPC system, a method for determining the optical properties of turbid medium is developed using time-resolved reflection and transmission measurements, and validated on solid and liquid phantoms. The feasibility and reliability of the time-domain FDOT methodology are experimentally validated with the multi-channel TCSPC system, on slab and cylinder phantoms, each embedding one or two fluorescent targets made from mixture of 1%-Intralipid solution and Cy5.5 or Indocyanine green (ICG) agent, the two fluorescent agents widely used in biological and biomedical studies. The results show that the approach retrieves the positions and shapes of the targets with a reasonable accuracy. Nevertheless, an investigation must be made in depth on system optimization of the measurement system, modification of the image reconstruction methodology and assessment of FDOT quantification.