Bioluminescence tomography (BLT) is a promising in vivo molecular imaging tool that allows non-invasive monitoring of physiological and pathological processes at the cellular and molecular levels. However, the accuracy of the BLT reconstruction is significantly affected by the forward modeling errors in the simplified photon propagation model, the measurement noise in data acquisition, and the inherent ill-posedness of the inverse problem. In this paper, we present a new multispectral differential strategy (MDS) on the basis of analyzing the errors generated from the simplification from radiative transfer equation (RTE) to diffusion approximation and data acquisition of the imaging system. Through rigorous theoretical analysis, we learn that spectral differential not only can eliminate the errors caused by the approximation of RTE and imaging system measurement noise but also can further increase the constraint condition and decrease the condition number of system matrix for reconstruction compared with traditional multispectral (TM) reconstruction strategy. In forward simulations, energy differences and cosine similarity of the measured surface light energy calculated by Monte Carlo (MC) and diffusion equation (DE) showed that MDS can reduce the systematic errors in the process of light transmission. In addition, in inverse simulations and in vivo experiments, the results demonstrated that MDS was able to alleviate the ill-posedness of the inverse problem of BLT. Thus, the MDS method had superior location accuracy, morphology recovery capability, and image contrast capability in the source reconstruction as compared with the TM method and spectral derivative (SD) method. In vivo experiments verified the practicability and effectiveness of the proposed method.

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X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality in optical molecular imaging, which has attracted more attention and has been widely studied. In XLCT, the accuracy and operational efficiency of an optical transmission model play a decisive role in the rapid and accurate reconstruction of light sources. For simulation of optical transmission characteristics in XLCT, considering the limitations of the diffusion equation (DE) and the time and memory costs of simplified spherical harmonic approximation equation (SPN), a hybrid light transport model needs to be built. DE and SPN models are first-order and higher-order approximations of RTE, respectively. Due to the discontinuity of the regions using the DE and SPN models and the inconsistencies of the system matrix dimensions constructed by the two models in the solving process, the system matrix construction of a hybrid light transmission model is a problem to be solved. We provided a new finite element mesh regrouping strategy-based hybrid light transport model for XLCT. Firstly, based on the finite element mesh regrouping strategy, two separate meshes can be obtained. Thus, for DE and SPN models, the system matrixes and source weight matrixes can be calculated separately in two respective mesh systems. Meanwhile, some parallel computation strategy can be combined with finite element mesh regrouping strategy to further save the system matrix calculation time. Then, the two system matrixes with different dimensions were coupled though repeated nodes were processed according to the hybrid boundary conditions, the two meshes were combined into a regrouping mesh, and the hybrid optical transmission model was established. In addition, the proposed method can reduce the computational memory consumption than the previously proposed hybrid light transport model achieving good balance between computational accuracy and efficiency. The forward numerical simulation results showed that the proposed method had better transmission accuracy and achieved a balance between efficiency and accuracy. The reverse simulation results showed that the proposed method had superior location accuracy, morphological recovery capability, and image contrast capability in source reconstruction. In-vivo experiments verified the practicability and effectiveness of the proposed method.