Three-Dimensional Reconstruction Methods For Bioluminecence Tomography

Optical molecular imaging is a powerful tool used in biomedical research.This noninvasive technology has led to widespread exploration of biological processes in vivo at cellular and molecular levels within intact living organisms.In particular,the development of OMI could help us understand more fully the functioning of diagnose disease earlier and speed along drug discovery,especially for cancer,which has a global increase in incidence rate.Bioluminescence tomography is one of the various modalities of OMI,which can localiza and quantify the cancer distribution using specifically targeted agents because of its high sensitivity.The imaging theory of Bioluminescence tomography has been preliminarily established.It mainly refers to the procedure of creating the object in 3D from a set of planar images in physical meaning.Because of the photo scattering effect in tissues,the 3D tomographic reconstruction of BLI suffers from the challenge of solving the ill-posed inverse problem.The ill-posed of reconstruction enhances the difficulty to solve and limits the accuracy of imaging.Therefore,the international community has been constantly exploring how to reduce the dependency with the rigorous imaging requirements,how to improve the quality and efficiency of the reconstruction method.Based on the background above,related research for bioluminescence tomography has been carried on in this thesis.This research focuses on reconstruction methods and prototype system of bioluminescence tomography to solve biomedical problems in practical application.In vivo experiments on small animals have been conducted to verify the feasibility of the proposed 3D reconstruction methods and the prototype system.The tasks are summarized as follows:1.A split Bregman iterative method and surrogate functions method(SBISF)has been presented for non-invasive in vivo 3D detection of small liver tumors in the mouse.The proposed use split Bregman iterative and surrogate Functions,which can can reduce the calculation amount of each iteration and guarantees the global convergence effectively.Numerical simulation experiments of multisource cases with comparative analyses were performed to evaluate the performance of the proposed method.A bead-implanted mouse and a breast cancer xenograft mouse model were employed to validate the feasibility of this method in in vivo experiments.The existing 3D reconstruction algorithms have partly solved the problems of accuracy and speed,while most experiments were based on numerical simulation,geometric phantoms,or a mouse phantom.Since the signal is usually much weaker in practical application,it is necessary to validate the algorithms with in vivo experiments based on the orthotopic mouse tumor model.This method takes advantage of X-ray computed tomography and multi-view bioluminescence imaging,providing anatomical structure and bioluminescence intensity information to reconstruct the size and location of tumors.It guarantees the accuracy,efficiency and reliability for 3D reconstruction by incorporating some mathematical strategies including specific iterative shrinkage and surrogate Functions.The findings indicate that a tiny lesion can be localized,and the computational efficiency is 1～3 orders of magnitude faster than the existing algorithms.2.A pure optical bioluminescence tomographic(POBT)system and a novel split Bregman method for 3D surface reconstruction has been presented.This method can reconstruct the 3D surface of an imaging subject based on a sparse set of planar white-light and bioluminescent images,so that the prior structural information can be offered for 3D tumor lesion reconstruction without the involvement of CT.The diffusion equation(DE)is utilized to depict how photons travel inside the mouse body,and the finite element(FEM)method is adopted to establish the linear relationship between the photon distribution on the surface and the unknown internal bioluminescence distribution inside the body.Here,the unknown bioluminescence intensity distribution,which represents the tumor location and size,was solved using L1 regularization for bioluminescence tomography based on the Split Bregman method.The technology can be effectively applied to the research of physiological metabolism and efficiency of reconstruction is higher.It is suitable for the simple and crude experimental environment.The performance of this novel technique was evaluated through the comparison with a conventional dual-modality tomographic(DMT)system and a commercialized optical imaging system(IVIS Spectrum)using three breast cancer xenografts.The results revealed that the new technique offered comparable in vivo tomographic accuracy with the DMT system(P>0.05)in much shorter data analysis time.It also offered significantly better accuracy comparing with the IVIS system(P<0.04)without sacrificing too much time.3.A multimodality molecular imaging system has been constructed with X-ray computed tomography and multi-view bioluminescence imaging.The imaging system aquire coregistered simultaneous optical and Micro-CT imaging,enabling the multimodality fusion for the 3D reconstruction.It aims to obtain more accurate surface photon density and to provide coregistered functional and structural information to improve the reconstruction results.It can be use for quantitatively assess of biological systems in vivo at molecular and anatomical structure levels.