We propose a novel prompt-gamma (PG) imaging modality for real-time monitoring in proton therapy: PG time imaging (PGTI). By measuring the time-of-flight (TOF) between a beam monitor and a PG detector, our goal is to reconstruct the PG vertex distribution in 3D. In this paper, a dedicated, non-iterative reconstruction strategy is proposed (PGTI reconstruction). Here, it was resolved under a 1D approximation to measure a proton range shift along the beam direction. In order to show the potential of PGTI in the transverse plane, a second method, based on the calculation of the centre of gravity (COG) of the TIARA pixel detectors’ counts was also explored. The feasibility of PGTI was evaluated in two different scenarios. Under the assumption of a 100 ps (rms) time resolution (achievable in single proton regime), MC simulations showed that a millimetric proton range shift is detectable at 2σ with 108 incident protons in simplified simulation settings. With the same proton statistics, a potential 2 mm sensitivity (at 2σ with 108 incident protons) to beam displacements in the transverse plane was found using the COG method. This level of precision would allow to act in real-time if the treatment does not conform to the treatment plan. A worst case scenario of a 1 ns (rms) TOF resolution was also considered to demonstrate that a degraded timing information can be compensated by increasing the acquisition statistics: in this case, a 2 mm range shift would be detectable at 2σ with 109 incident protons. By showing the feasibility of a time-based algorithm for the reconstruction of the PG vertex distribution for a simplified anatomy, this work poses a theoretical basis for the future development of a PG imaging detector based on the measurement of particle TOF.

Within the frame of the CLaRyS collaboration, we discuss the assets of using a reduced-intensity in vivo treatment control phase during one or a few beam spots at the beginning of a particle therapy session. By doing so we can improve considerably the conditions for secondary radiation detection and particle radiography. This also makes Time-of-Flight (ToF) resolutions of 100 ps rms feasible for both the transmitted particles and secondary radiations, by means of a single-projectile counting mode using a beam-tagging monitor with time and position registration. This opens up new perspectives for prompt-gamma timing and Compton imaging for range verification. ToF-based proton computed tomography (CT) and ToF-assisted secondary proton vertex imaging in carbon therapy are also discussed, although for the latter, no evidence of any benefit at small observation angles is anticipated. The reduction of the beam intensity during one or a few spots on the various accelerators for particle therapy should not significantly reduce the patient workflow.

We recently proposed a new approach for the real-time monitoring of particle therapy treatments with the goal of achieving high sensitivities on the particle range measurement already at limited counting statistics. This method extends the Prompt Gamma (PG) timing technique to obtain the PG vertex distribution from the exclusive measurement of particle Time-Of-Flight (TOF). It was previously shown, through Monte Carlo simulation, that an original data reconstruction algorithm (Prompt Gamma Time Imaging) allows to combine the response of multiple detectors placed around the target. The sensitivity of this technique depends on both the system time resolution and the beam intensity. At reduced intensities (Single Proton Regime—SPR), a millimetric proton range sensitivity can be achieved, provided the overall PG plus proton TOF can be measured with a 235 ps (FWHM) time resolution. At nominal beam intensities, a sensitivity of a few mm can still be obtained by increasing the number of incident protons included in the monitoring procedure. In this work we focus on the experimental feasibility of PGTI in SPR through the development of a multi-channel, Cherenkov-based PG detector with a targeted time resolution of 235 ps (FWHM): the TOF Imaging ARrAy (TIARA). Since PG emission is a rare phenomenon, TIARA design is led by the concomitant optimisation of its detection efficiency and Signal to Noise Ratio (SNR). The PG module that we developed is composed of a small PbF$$_{2}$$ 2 crystal coupled to a silicon photoMultiplier to provide the time stamp of the PG. This module is currently read in time coincidence with a diamond-based beam monitor placed upstream the target/patient to measure the proton time of arrival. TIARA will be eventually composed of 30 identical modules uniformly arranged around the target. The absence of a collimation system and the use of Cherenkov radiators are both crucial to increase the detection efficiency and the SNR, respectively. A first prototype of the TIARA block detector was tested with 63 MeV protons delivered from a cyclotron: a time resolution of 276 ps (FWHM) was obtained, resulting in a proton range sensitivity of 4 mm at 2$$\sigma$$ σ with the acquisition of only 600 PGs. A second prototype was also evaluated with 148 MeV protons delivered from a synchro-cyclotron obtaining a time resolution below 167 ps (FWHM) for the gamma detector. Moreover, using two identical PG modules, it was shown that a uniform sensitivity on the PG profiles would be achievable by combining the response of gamma detectors uniformly distributed around the target. This work provides the experimental proof-of-concept for the development of a high sensitivity detector that can be used to monitor particle therapy treatments and potentially act in real-time if the irradiation does not comply to treatment plan.