Fluorescence molecular tomography can combine two-dimensional fluorescence imaging with anatomical information to reconstruct three-dimensional images of tumors. Reconstruction based on traditional regularization with tumor sparsity priors does not take into account that tumor cells form clusters, so it performs poorly when multiple light sources are used. Here we describe reconstruction based on an "adaptive group least angle regression elastic net" (AGLEN) method, in which local spatial structure correlation and group sparsity are integrated with elastic net regularization, followed by least angle regression. The AGLEN method works iteratively using the residual vector and a median smoothing strategy in order to adaptively obtain a robust local optimum. The method was verified using numerical simulations as well as imaging of mice bearing liver or melanoma tumors. AGLEN reconstruction performed better than state-of-the-art methods with different sizes of light sources at different distances from the sample and in the presence of Gaussian noise at 5-25%. In addition, AGLEN-based reconstruction accurately imaged tumor expression of cell death ligand-1, which can guide immunotherapy.
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