Methodologies Of Optical Structure Modeling And Advanced Image Reconstruction For The Small-animal Fluorescence Molecular Tomography

Fluorescence molecular tomography(FMT)which combines the advantages of both the specific fluorescent molecular labeling technique and the near-infrared diffuse optical tomography(DOT),has been expected to be employed for visualizing the biochemical reaction processes related to the cells or molecules in the living tissue.However,for the small animal in-vivo imaging,the spatial resolution,quantitativeness and robustness of the current FMT method are still need to be improved due to the difficulty in obtaining anatomical structures and effective background optical parameters and the high ill-posedness of the reconstruction process.For the application of X-ray Computed Tomography(XCT)/DOT/FMT multi-models imaging of the small animal model,this thesis mainly focuses on developing the methods for obtaining prior anatomical structures and priori optical structures in vivo,and seeking a method which can overcome the ill-posedness effectively in FMT reconstruction.A non-rigid XCT image registration scheme for creating anatomical structures of the target mouse is proposed.At first,the standard XCT volume of the Digimouse is registered to the target XCT volume of the target mouse by a two-step process of the point-matching based pre-registration and the block-matching based post-registration.Then,the displacement field generated from the registration process is applied to the standard atlas for approximately constructing the anatomical atlas of the target mouse.Both the numerical simulation and mouse experiment results demonstrated that the standard XCT volume can be effectively registered to the target XCT volume and the anatomical atlas of the target mouse can be approximately constructed.An atlas-registration-based DOT strategy for acquiring organ-oriented tissue optical properties in-vivo is proposes.At first,an XCT experiment and a three-dimensional time-domain(TD)-DOT measurement are conducted on the target mouse.Then,the anatomical atlas of the target mouse is obtained with the proposed registration method.Finally,the registered atlas is applied as a priori anatomical structure for constraining the region-based featured-data reconstruction scheme for TD-DOT.The validity and applicability of the proposed method are firstly tested using simulated scenarios,and then a pilot experiment is performed on living mouse models which presents in-vivo measurement of the optical properties of the major organs.An early-photon FMT reconstruction approach based on the instrumental response function(IRF)calibrated perturbation Monte-Carlo(pMC)modeling with a time-resolved overlap-delaying time-gate data type is presented.At first,the fluorescence Jacobians are calculated with the pMC method and are convoluted by the measured IRF for each source-detector pair.Secondly,the measured time-of-flight distributions of excitation and emission light are processed with an overlap-delaying time-gate technique to enhance the noise robustness.Thirdly,the photons detected in the early time-gates are chosen for image reconstruction with the purpose of improving the performance of early-photon FMT.The phantom experiment results lead to the conclusions that the proposed method could effectively improve the quality of the reconstructed fluorescence images as compared to the traditional early-photon FMT.In order to solve the problems in the current FMT technology,this thesis proposes an anatomical structure acquisition method based on XCT image registration,a registered-atlas constrained DOT reconstruction,and a time-resolved early-photon scheme for FMT with pMC modeling.The effectiveness and improvement of the related algorithms have been validated by numerical simulations and phantom or in vivo mouse experiments using a CT-analogous scanning TD-DOT/FMT system.