Towards real-time ion range verification via hybrid Compton-PET 3D imaging at isochronous cyclotrons
Range uncertainties remain a major limitation to the full clinical exploitation of proton therapy, motivating reliable in-vivo range-verification techniques. This work presents an experimental investigation of a hybrid Prompt-Gamma Imaging (PGI)--Positron-Emission Tomography (PET) concept at the isochronous cyclotron of the West German Proton Therapy Centre under clinically representative pencil-beam-scanning conditions. Because this accelerator delivers a quasi-continuous beam, a pulsed shoot-and-step structure was imposed to mimic the interruptions associated with clinical energy-layer switching. This enabled PGI during irradiation and PET and delayed Compton imaging during beam-off intervals within the same sequence. Four two-plane Compton cameras were arranged in a co-planar cross-shaped geometry around the beam isocenter. Polyethylene phantoms were irradiated with 100~MeV protons at known positions along the beam axis. Their positions were estimated from reconstructed one-dimensional profiles using supervised machine-learning models trained exclusively on Monte Carlo simulations. PET achieved the best performance, with a root-mean-square deviation of 0.8~mm, followed by PGI with 1.6~mm. Delayed Compton imaging based on e$^{+}$ annihilation photons and $^{10}$C$^{*}$ decays yielded 2.4~mm and 3.8~mm, respectively. PET retained good performance down to 1% of the original event statistics, whereas PGI became increasingly statistics-limited. These results demonstrate the complementary strengths of hybrid PGI--PET and support its development towards millimetre-scale proton-range verification under clinically relevant irradiation conditions.