MR-only simulations provide pseudo-CT images which are segmented into 5 kinds of tissues from DIXON-based images. However, it is difficult to register pseudo-CT images to cone-beam CT (CBCT) images collected for image-guided radiation therapy (IGRT), because of the lack of contrasts among tissues. We validated gaps of IGRT between pseudo-CT or planning CT and CBCT for patients without implanted markers. We also propose calcification-assisted registration for MR-only simulation. We conducted retrospective analyses to verify the registration accuracy in 15 patients who underwent volumetric modulated arc therapy (VMAT) for prostate cancer. They underwent planning CT and pseudo-CT. Pseudo-CT images after deformable image registration (DIR) to planning CT images were rendered automatic pelvic bone matching to CBCT images. Patient positions on the pseudo-CT images after DIR were shifted on the basis of tissues around the prostate. We compared registration gaps between the images of planning CT and pseudo-CT with DIR, assuming that the tissue-based matching between the planning CT and CBCT was the gold standard. To the pseudo-CT images with DIR, calcifications detected on planning CT were added. We validated IGRT accuracy for a calcification-assisted registration. The absolute registration errors of the pseudo-CT, in comparison with the planning CT, were 0.34  ±  0.50 (lateral), 1.3  ±  1.3 (longitudinal), and 1.1  ±  1.0 mm (vertical). The absolute registration errors of the pseudo-CT with calcification contouring, in comparison with the planning CT, were 0.41  ±  1.0 (lateral), 0.87  ±  0.92 (longitudinal), and 0.74  ±  0.64 mm (vertical). Reduced absolute registration errors were observed in the proposed approach in the longitudinal (P  <  0.01) and vertical (P  <  0.01) dimensions when using calcification-assisted registration. The tissue-based registration using the MR-only simulation was not sufficient for use in patients with prostate cancer without implanted markers. The calcification-assisted registration might help to improve IGRT accuracy using MRI alone.

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