2.5. Reference CT (rCT) generation

While a measured CT scan would be the ideal reference for validating the sCT generation method, it was not appropriate to expose the normal volunteers to the associated ionizing radiation. Accordingly, we used a template‐ or model‐based method using normal, average human structure, to create a reference CT (rCT) for testing the proposed method. The template method has been shown to be able to generate accurate thoracic CT for PET AC and radiation treatment plans for people with normal anatomy^{34, 35} and would be applicable for normal volunteers in order to create a reference for comparison. Male and female XCAT computational human models were used in this study for the template CT generation.³⁶ Using XCAT, a library of XCAT CT and Dixon_water MR was generated. To account for the mathematical morphology of the bone skeleton in XCAT CT (which did not segment bone marrow³⁷), bone from de‐identified measured CT data replaced the bone skeleton in the XCAT so that the final reference CT would contain accurate bone anatomy.

In short, rCT generation is done as follows. First, template MR is registered to the volunteer's MR including manual, landmark‐based 3D b‐spline registration³⁸ and diffeomorphic local‐phase registration.³⁹ Second, the CT bone model of the template CT would be transformed to match the volunteer's MR according to the deformation field estimated by the MR‐to‐MR registration. Finally, the whole XCAT template CT would be warped to match MR in order to generate the final rCT for evaluation. In this study, the sCT was designed for MR‐based PET AC. For this reason, a 4‐mm isotropic Gaussian filter was applied on both sCT and rCT for resolution matching.^{40, 41}