Research On Methods To Improve The Localization And Quantitative Performance Of Fluorescence Molecular Tomography-X Ray Computed Tomography

It is important for small animal models of disease and drug development to noninvasively get the localization and quantitative information of the fluorescent targets associate with the molecular and cellular.The hybrid fluorescence molecular tomography and X-ray computed tomography(FMT-XCT)plays an important role in this respect.In recent years,the nonlinear nBorn method based hybrid FMT-XCT has been widely used in the research of mouse models of diseases,including lung cancer,brain tumors,atherosclerosis,and Alzheimer's disease.However,the inverse problem of FMT-XCT is severely ill-posed and,hence,the localization and quantitative performance of FMT-XCT is easily affected by the experimental noise,the absorption and scattering heterogeneities of the samples,and the performance of the CCD.So,in this work,the core problem of how to improve the localization and quantitative performance of FMT-XCT has been studied.The study is separated into the following three parts.First,the basic theory and imaging method of FMT-XCT are studied.The main researches includes the study of the basic principle of the forward and inverse problem of FMT and XCT,the composition of FMT-XCT system and how it works.Then the nBorn method and iterative reweighted L1 regularization based FMT-XCT method is established.These studies help provide reliable theoretic and experimental basis for further researches.To weaken the influence of the absorption and scattering heterogeneities on the localization and quantitative performance of FMT-XCT,in this study,a novel linear nBorn method is proposed.With this method,the emission data for each projection is normalized with the average excitation data of all detectors.It offers advantages of eliminating the experimental factors,the unknown source strength,and the coupling losses.Moreover,the relative distributions of the normalized measurements are consistent with those of the emission data and the acquired excitation data are averaged which is effective in suppressing excitation noise.The research results indicate that the linear nBorn method is robust to the absorption and scattering heterogeneities and provides better localization and quantitative performance when compared with the nonlinear nBorn method.The limited dynamic range of a CCD severely diminishes the imaging quality of FMT-XCT for fluorescent targets with large concentration differences.To overcome this problem and further improve the localization and quantitative performance,an HDR-FMT method is proposed.Under the multiple-exposure scheme,HDR fluorescence projection images are constructed and used in FMT-XCT reconstruction.Iterative reweighted L1 regularization is used in the image reconstruction to compensate for the time consumed with the use of a multiple-exposure scheme.The research results shows that the HDR method can effectively enhance the dynamic range of fluorescence projection images and HDR-FMT has a better localization performance than conventional FMT-XCT reconstruction using low-dynamic-range fluorescence projection images.In conclusion,the linear nBorn method and HDR-FMT method provided here can effectively improve the localization and quantitative performance of FMT-XCT in the presence of complex heterogeneities or when the dynamic range of CCD detector is low.