Periodic Reporting for period 1 - PGTI (Prompt Gamma Time Imaging: a new medical-imaging modality for adaptive Particle Therapy)
Periodo di rendicontazione: 2022-10-01 al 2025-03-31
Particle Therapy (PT) is potentially the most conformal and selective form of radiotherapy, but its clinical outcome is still limited, mainly because of the numerous sources of uncertainties affecting both treatment planning and delivery. The objective technical complexity of predicting and verifying the ion path in the patient has led to conservative treatments that, in order to increase safety, sacrifice efficacy. Having the full control of the dose gradient within the patient in real time would allow to fully exploit the ballistic advantage of PT. The healthy-tissue sparing effect can be enormous, further encouraging the use of PT for paediatric malignancies. Alternatively, the target dose could be increased to achieve better tumour control, and dose escalation procedures could be envisaged to treat radio-resistant tumours.
With the aim of increasing both safety and efficacy, this project proposes a new medical-imaging modality, Prompt Gamma Time Imaging (PGTI), and the development of a dedicated fast gamma detector, TIARA (Time-of-flight Imaging ARrAy), to monitor PT treatments in real-time. They exploit the signal of the secondary prompt gamma-rays emitted from nuclear interactions in the patients to recover information on ion range, tissue density and dose.
TIARA will be composed of 30 gamma detection modules based on monolithic Cherenkov radiators uniformly distributed around the patient, and read in temporal coincidence with a dedicated beam monitor, to allow the measurement of the total Time-Of-Flight (TOF) of the incident ion and the PG with a temporal resolution of the order of 100 ps rms. The resolution of an inverse problem (the PGTI algorithm) makes it possible to determine the spatial distribution of the PG vertices, which is strongly correlated with the particle path in the patient, but also to the densities of tissues intersected by the beam. This will allow to correlate the images provided by PGTI to real-time dose distributions, in order to enable the use of this technique for adaptive dosimetry. PGTI will be also explored as a potential approach to proton tomography. If this project is successful, it will allow, for the first time, to control the uncertainties affecting both treatment planning and treatment delivery with a unique device. PGTI may be the missing step towards the birth of image-guided particle therapy.
With the aim of increasing both safety and efficacy, this project proposes a new medical-imaging modality, Prompt Gamma Time Imaging (PGTI), and the development of a dedicated fast gamma detector, TIARA (Time-of-flight Imaging ARrAy), to monitor PT treatments in real-time. They exploit the signal of the secondary prompt gamma-rays emitted from nuclear interactions in the patients to recover information on ion range, tissue density and dose.
TIARA will be composed of 30 gamma detection modules based on monolithic Cherenkov radiators uniformly distributed around the patient, and read in temporal coincidence with a dedicated beam monitor, to allow the measurement of the total Time-Of-Flight (TOF) of the incident ion and the PG with a temporal resolution of the order of 100 ps rms. The resolution of an inverse problem (the PGTI algorithm) makes it possible to determine the spatial distribution of the PG vertices, which is strongly correlated with the particle path in the patient, but also to the densities of tissues intersected by the beam. This will allow to correlate the images provided by PGTI to real-time dose distributions, in order to enable the use of this technique for adaptive dosimetry. PGTI will be also explored as a potential approach to proton tomography. If this project is successful, it will allow, for the first time, to control the uncertainties affecting both treatment planning and treatment delivery with a unique device. PGTI may be the missing step towards the birth of image-guided particle therapy.
Within the first year, it was possible to finalise the designs of the TIARA detector block and a beam monitor that meet the targeted specifications in terms of temporal resolution and detection efficiency. The beam monitor also allows the measurement of the impact point of the incident particle with a spatial resolution of less than 2 mm for the single particle.
A TIARA prototype including 8 block detectors (in the photo) has recently been realised. Numerous experiments under proton and carbon beams conducted in different clinical centers have demonstrated the feasibility of the PGTI approach for irradiations carried out with cyclotrons, synchro-cyclotrons (at Centre Antoine Lacassagne, Nice, France) and synchrotrons (at CNAO, Pavia, Italy). The excellent temporal resolution of the system, as well as its insensitivity to neutrons, the main source of noise for this application, contribute to the measurement of TOF distributions characterized by a very high signal-to-noise ratio. This makes it possible to achieve a range accuracy below 2 mm (at 2 sigma) at the scale of a single irradiation spot (e.g. 10^7 protons), thanks to the measurement of the width of the TOF distribution. The plot shows the TOF distributions obtained from the irradiation of the sinus of an anthropomorphic phantom head with 148 MeV protons at the ProteusOneTM accelerator: data obtained with the sinus empty (red) or filled with gel (blue) are clearly separated. These data also make it possible to measure the variation of the PG production rate along the hadron path and therefore to obtain information on the density and stopping powers of the tissues intersected, opening up prospects for the use of TIARA for proton imaging.
A TIARA prototype including 8 block detectors (in the photo) has recently been realised. Numerous experiments under proton and carbon beams conducted in different clinical centers have demonstrated the feasibility of the PGTI approach for irradiations carried out with cyclotrons, synchro-cyclotrons (at Centre Antoine Lacassagne, Nice, France) and synchrotrons (at CNAO, Pavia, Italy). The excellent temporal resolution of the system, as well as its insensitivity to neutrons, the main source of noise for this application, contribute to the measurement of TOF distributions characterized by a very high signal-to-noise ratio. This makes it possible to achieve a range accuracy below 2 mm (at 2 sigma) at the scale of a single irradiation spot (e.g. 10^7 protons), thanks to the measurement of the width of the TOF distribution. The plot shows the TOF distributions obtained from the irradiation of the sinus of an anthropomorphic phantom head with 148 MeV protons at the ProteusOneTM accelerator: data obtained with the sinus empty (red) or filled with gel (blue) are clearly separated. These data also make it possible to measure the variation of the PG production rate along the hadron path and therefore to obtain information on the density and stopping powers of the tissues intersected, opening up prospects for the use of TIARA for proton imaging.
The use of pure Cherenkov radiators for the detection of prompt gamma rays was considered atypical if not unfeasible a few years ago, but today we know that this is a game changer for this application. Unfortunately, conventional gamma detectors are also very good neutron detectors. In an environment where neutron contamination may be very high, as in a PT treatment, it is especially important being able to separate the prompt gamma signal from that of neutrons in order to improve the measurement accuracy. Cherenkov detectors, being neutron-blind, offer the highest sensitivity and made it possible for the TIARA prototype, to achieve a range accuracy below 2 mm (at 2 sigma). At low beam intensity, this accuracy can be achieved already within the first irradiation spot (e.g. 10^7 protons), while the most advanced techniques available today need at least 10 times more protons to provide the same result. In this sense, TIARA could pave the way to real-time dosimetry.