Patient-specific stopping power calibration of treatment planning x-ray CT using integrated depth-dose profiles acquired by proton transmission imaging-a feasibility study.

Objective.Range uncertainties in proton therapy largely arise from the semi-empirical conversion of x-ray computed tomography (CT) Hounsfield Units to stopping power relative to water (RSP), requiring generous safety margins or robust optimization. Pencil beam-wise integrated depth-dose profiles (IDDs), obtained via proton transmission imaging using a particle integrating detector, can be combined with the treatment planning CT to obtain patient-specific conversion curves. Existing calibration approaches rely on projection images or water-equivalent path length (WEPL) histograms derived from IDDs via signal decomposition or deconvolution. A direct optimization approach based on the acquired IDD signal is proposed, avoiding the need for decomposition or deconvolution and their associated WEPL accuracy and resolution limitations.Approach.The RSP conversion curve is iteratively optimized using Monte Carlo-simulated IDDs acquired from two orthogonal projection angles in a line-scan proton imaging setup. The differentiable implementation of the forward projection operator is embedded in a gradient-based optimization scheme.Main results.The proposed IDD-based optimization approach significantly reduces the calibration error compared to the initial guess. The median mean absolute percentage error on a set of axial CT slices decreases from 1.88% to 0.58%, with a median computation time of 5.47 h per slice. The optimized calibration improves dose accuracy for an exemplary treatment pencil beam. Increasing the spot spacing by a factor of ten decreases the computation time to 0.60 h with minimal loss of accuracy. Using a single projection angle yields comparable results to using both projections (0.64% vs 0.57%). With current detector depth resolutions of2 mm, calibration accuracy of0.7% is achievable, with potential improvements using finer-resolution detectors.Significance.Particle integrating detectors offer potential for clinical translation due to lower cost and complexity. Direct optimization on IDDs using a differentiable forward operator enables accurate, fully automated calibration, improving upon earlier manual IDD-based or automated WEPL-based approaches.