Abstract.SignificanceFluorescence molecular tomography (FMT) is a promising imaging modality, which has played a key role in disease progression and treatment response. However, the quality of FMT reconstruction is limited by the strong scattering and inadequate surface measurements, which makes it a highly ill-posed problem. Improving the quality of FMT reconstruction is crucial to meet the actual clinical application requirements.AimWe propose an algorithm, neighbor-based adaptive sparsity orthogonal least square (NASOLS), to improve the quality of FMT reconstruction.ApproachThe proposed NASOLS does not require sparsity prior information and is designed to efficiently establish a support set using a neighbor expansion strategy based on the orthogonal least squares algorithm. The performance of the algorithm was tested through numerical simulations, physical phantom experiments, and small animal experiments.ResultsThe results of the experiments demonstrated that the NASOLS significantly improves the reconstruction of images according to indicators, especially for double-target reconstruction.ConclusionNASOLS can recover the fluorescence target with a good location error according to simulation experiments, phantom experiments and small mice experiments. This method is suitable for sparsity target reconstruction, and it would be applied to early detection of tumors.