Proton CT on biological phantoms for x-ray CT calibration in proton treatment planning

To present and characterize a novel method for X-ray CT (xCT) calibration in proton treatment planning, based on proton CT (pCT) measurements on biological phantoms. Approach: A pCT apparatus was used to perform direct measurements of 3D stopping power relative to water (SPR) maps on stabilized, biological phantoms. Two single-energy xCT calibration curves - i.e. tissue substitutes and stoichiometric - were compared to pCT data. Moreover, a new calibration method based on these data was proposed, and verified against intra- and inter-species variability, dependence on stabilization, beam-hardening conditions, and analysis procedures. Main results: Biological phantoms were verified to be stable in time, with a dependence on temperature conditions, especially in the fat region: (-2.50.5) HU/°C. The pCT measurements were compared with standard xCT calibrations, revealing an average SPR discrepancy within ±1.60% for both fat and muscle regions. In the bone region the xCT calibrations overestimated the pCT-measured SPR of the phantom, with a maximum discrepancy of about +3%. As a result, a new cross-calibration curve was directly extracted from the pCT data. Overall, the SPR uncertainty margin associated with this curve was below 3%; fluctuations in the uncertainty values were observed across the HU range. Cross-calibration curves obtained with phantoms made of different animal species and anatomical parts were reproducible with SPR discrepancies within 3%. Moreover, the stabilization procedure did not affect the resulting curve within a 2.2% SPR deviation. Finally, the cross-calibration curve was affected by the beam-hardening conditions on xCTs, especially in the bone region, while dependencies below 2% resulted from the image registration procedure. Significance: Our results showed that pCT measurements on biological phantoms may provide an accurate method for the verification of current xCT calibrations and may represent a tool for the implementation of a new calibration method for proton treatment planning.