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Cerenkov luminescence tomography (CLT) is a promising imaging tool for obtaining three-dimensional (3D) non-invasive visualization of the <italic>in vivo</italic> distribution of radiopharmaceuticals. However, the reconstruction performance remains unsatisfactory for biomedical applications because the inverse problem of CLT is severely ill-conditioned and intractable. In this study, therefore, a novel non-negative iterative convex refinement (NNICR) approach was utilized to improve the CLT reconstruction accuracy, robustness as well as the shape recovery capability. The spike and slab prior information was employed to capture the sparsity of Cerenkov source, which could be formalized as a non-convex optimization problem. The NNICR approach solved this non-convex problem by refining the solutions of the convex sub-problems. To evaluate the performance of the NNICR approach, numerical simulations and <italic>in vivo</italic> tumor-bearing mice models experiments were conducted. Conjugated gradient based Tikhonov regularization approach (CG-Tikhonov), fast iterative shrinkage-thresholding algorithm based Lasso approach (Fista-Lasso) and Elastic-Net regularization approach were used for the comparison of the reconstruction performance. The results of these experiments demonstrated that the NNICR approach obtained superior reconstruction performance in terms of location accuracy, shape recovery capability, robustness and <italic>in vivo</italic> practicability. It was believed that this study would facilitate the preclinical and clinical applications of CLT in the future.

Non-Negative Iterative Convex Refinement Approach for Accurate and Robust Reconstruction in Cerenkov Luminescence Tomography