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This study aimed to investigate the reliability of pseudo-computed tomography (pseudo-CT) imaging based on ultrasound (US) deformation fields under different binary masks in radiotherapy.We used 3-dimensional (3D) CT and US images, including those acquired during CT simulation positioning, and cone-beam CT (CBCT) and US images acquired 1 week after treating 3 patients with cervical cancer. Image data of 3 different layers were selected from the US images, and 3D CT images of each patient were selected. For US image registration, the following were created and applied: binary masks of the region of interest overlapping (ROIO) between the US image based on simulation positioning and US image for positioning verification, region of interest (ROI), whole overlapping (wholeO), and whole imaging region (whole). Accordingly, the deformation field was obtained and applied to CT images (CTsim), and different pseudo-CT images were acquired. Similarities between the pseudo-CT and CBCT images were compared, and registration accuracies between pseudo-CT images under different binary masks and CTsim were compared and discussed.A pair t test was conducted to normalized mutual information values of the registration accuracy between the pseudo-CT image based on ROIO binary mask and CTsim with other methods (P < .05), and the difference was statistically significant. A pair t test of normalized gray mean-squared errors was also performed (P < .05), and the difference was statistically significant. The similarity function means between pseudo-CT, that is, based on ROIO, ROI, wholeO, whole, and no binary mask, and CBCT were 0.9084, 0.8365, 0.7800, 0.6830, and 0.5518, respectively.Pseudo-CT based on ROIO binary mask best matched with CTsim and achieved the highest similarity with CBCT.