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PURPOSE For cone-beam computed tomography (CBCT) systems, we propose a sphere phantom based method to estimate the full 3-dimensional (3-D) modulation transfer function (MTF). METHODS The FDK reconstruction of CBCT system in a local region was modeled by triple convolution operator. Afterward, we calculated the directional projections of ideal and reconstructed sphere phantoms into a 2-D plane for multiple views. To estimate the projected 3-D point spread function (PSF), we applied the 2-D Richardson-Lucy deconvolution with Tikhonov-Miller (RL-TM). After estimating the projected 3-D PSF from multiple views, the full 3-D PSF was estimated by performing filtered backprojection. Then, the full 3-D MTF was calculated by taking the modulus of the Fourier transform of the estimated 3-D PSF. To validate the proposed method, we reconstructed sphere phantoms from simulation and experiment data. We simulated ideal 3-D MTFs and compared them with the estimated 3-D MTFs along the fz-, fx-, and f45° -directions. The full-width at half-maximum (FWHM) and full-widthat tenth-maximum (FWTM) values were compared between ideal and estimated 3-D MTFs. RESULTS The estimated 3-D MTFs from both the simulation and experiment results show qualitative similarity in their shapes with the ideal 3-D MTFs; FWHM and FWTM results quantitatively show that the proposed method provides reliable estimation performance. In particular, the estimated 3-D MTF in a missing cone region was correctly matched with the corresponding ideal 3-D MTF. CONCLUSIONS In this work, we proposed a full 3-D MTF estimation method for CBCT systems. Based on the results, we believe that the proposed method can be used to evaluate the spatial resolution performance of CBCT systems.