Projetc ID: LIDER/26/0157/L-8/16/NCBR/2017
Name of the programme: LIDER VIII
Project title: J-PET technology for proton beam therapy range monitoring (link)
Principial Investigator: Dr. inż. Antoni Ruciński
Realization period: 01.04.2018 – 31.03.2022
Budget: 1 200 000 PLN
This project aims to study and perform pre-clinical tests and as a consequence to propose a technological solution to monitor beam range in proton beam therapy. We aim to perform the first worldwide simulations and experimental tests to assess the feasibility of the J-PET detector technique for proton beam therapy range monitoring. We performed pre-clinical tests of developed technology with the purpose to implement it in proton beam therapy centre in Krakow and other centers abroad. The result of proposed study will be the design of a range monitoring detector prototype exploring J-PET technology.
Physical and biological range uncertainties limit the clinical potential of Proton Beam Therapy (PBT). Our team study the feasibility of Jagiellonian-PET detector technology for proton beam therapy range monitoring by means of MC simulations of the β + activity induced in a phantom by proton beams and present preliminary results of PET image reconstruction.
A single detection unit of the J-PET scanner consists of a 50 cm long and 6×24 mm2 intersection size scintillator strip. The light pulses produced in the strip by 511 keV back-to-back photons propagate to its edges where they are converted into electrical signals by photomultipliers (PMT). The interaction position of the photon with the detector is estimated from the time difference between the PMT signals located at the ends of the strip. A J-PET module consists of 13 scintillator strips read-out through a single front-end electronics and a FPGA-based DAQ system. More about J-PET you can find here: http://koza.if.uj.edu.pl/pet/
Implementation of the PET simulation framework
We implemented the ProTheRaMon framework [Publication 1] for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). The ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility.
The ProTheRaMon framework is based on GATE Monte Carlo software, the CASTOR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing stages (see Fig. 1), that can be further optimized according to the user’s needs and specific settings of a given proton therapy facility and PET scanner design.
Fig. 1. Graphical illustration of the five stages of the ProTheRaMon framework, software tools used by each of the stages, as well as data required for each of the stages. Blue refers to the input data for each stage, red refers to data that are treated as input data for one stage but was produced by previous stages.
We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment.
Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github (https://github.com/borysd/ProTheRaMon).
Simulations of J-PET scanner for intra-treatment proton beam range monitoring
We investigated the feasibility of the Jagiellonian Positron Emission Tomography (J-PET) scanner for intra-treatment proton beam range monitoring [Publication 2]. We performed Monte Carlo simulation studies with GATE and PET image reconstruction with CASToR to compare six J-PET scanner geometries (three dual-heads and three cylindrical). We simulated proton irradiation of a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out Bragg Peak (SOBP) of various ranges. We evaluated the sensitivity, precision, and cost-effectiveness of geometries shown in Fig. 2.
Fig. 2. The J-PET based geometrical configurations proposed for application in proton therapy range monitoring. We investigated: single layer cylinder (A), double layer cylinder (B), triple layer cylinder (C), single layer dual-head (D), double layer dual-head (E), and triple layer dual-head (F) configurations. A cylindrical water (blue) phantom was isocentrically positioned inside each of the configurations for simulations of proton beams shown with purple arrows.
The investigations indicate that the double-layer cylindrical and triple-layer double-head configurations are the most promising for clinical application. We found that the scanner sensitivity is of the order of 10^(-5) coincidences per primary proton, while the precision of the range assessment for both SPB and SOBP irradiation plans is below 1 mm. Among the scanners with the same number of detector modules, the best results are found for the triple-layer dual-head geometry. We performed simulation studies demonstrating that the feasibility of the J-PET detector for PET-based proton beam therapy range monitoring is possible with reasonable sensitivity and precision enabling its pre-clinical tests in the clinical proton therapy environment.
Patient simulation studies
Patient simulation studies investigated the feasibility of using J-PET in two different configurations for proton range monitoring, by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland [Publication 3].
In simulating the irradiation of the patients, discrepancies between the prescribed and delivered treatments were artificially introduced by means of shifts in patient positioning of 2, 4, 7, and 10 mm and in the Hounsfield unit (HU)-to-relative proton stopping power (RPSP) calibration curve of 2%. A dual-layer, full-ring J-PET geometry was simulated in an in-room monitoring scenario, acquiring data after the delivery of the final field of the treatment plan. A triple-layer, dual-head J-PET geometry was simulated in an in-beam protocol, consisting of the acquisition of data immediately after the delivery of the first field. The distribution of range shifts in reconstructed PET activity was visualized in the beam’s eye view of the last field delivered before each PET scan and its mean used as a predictor of the loss of dose conformation, measured from simulation using the mean range shifts in dose. A linear prediction model was constructed for each individual patient, with a median value for the coefficient of determination r^2 = 0.89 (in-room) and 0.85 (in-beam). An equivalent model including data from all patients resulted in r^2 = 0.85 (in-room) and 0.75 (in-beam). The precision of the prediction models for individual patients and patient cohort serve as a measure of the sensitivity of the proposed scanners to shifts in proton range for individual treatment plans.
These results are a measure of the capability of J-PET scanners to detect small discrepancies between the prescribed and delivered proton treatments. They also open up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment.
Experiments with the J-PET detector and proton beams at CCB
In order to carry out experimental work with the J-PET detector and the proton beam, the prototype of the J-PET detector was transferred from the laboratories of the Jagiellonian University to CCB IFJ PAN for a period of 10 days (two weekends) on October 16-25, 2021. 10 homogeneous gel phantoms with external dimensions of 20x20x15 cm^3 were prepared, made of PMMA with a thickness of 8 mm and filled with demineralized water with dissolved AGAR. Gel phantoms, unlike water phantoms, prevent the movement of radioactive isotopes formed as a result of irradiation. The heterogeneous CIRS phantom was also used for the experiment. For each gel phantom, irradiation plans were prepared for four cubes (Spread Out Bragg Peak, SOBP) placed in the corners of the phantom, each cube with transverse dimensions of 5×5 cm^2, modulation 5 cm, and ranges of 100, 103, 108 and 115 mm and 100, 104, 110, and 119 (Fig. 1, right). The average dose in SOBP cubes was 2 Gy, 4 Gy, 8 Gy and 16 Gy, respectively. GATE Monte Carlo simulations were performed and beta+ activity measurements were made for these plans. Fig. 1 (left) shows the J-PET detector in a three-layer, two-head configuration and a gel phantom prepared for irradiation in the treatment room of the CCB IFJ PAN gantry. During irradiation and within 30′ after irradiation of each individual cube, a signal was collected and used later to reconstruct the PET image.
Fig. 3. J-PET detector in a tripple-layer, dual-head configuration and a gel phantom prepared for irradiation in the CCB IFJ PAN gantry treatment room visible from a distance (left panel) and zoomed-in (right panel).
Fig. 4. Transverse view of the irradiation plan of the gel phantom (left panel) and views in the direction of irradiation with a section through each pair of SOBPs with different ranges (middle and right panels).
- D. Borys, …, A. Rucinski et al., ProTheRaMon—a GATE simulation framework for proton therapy range monitoring using PET imaging, Phys. Med. Biol. 2022 67:224002, https://doi.org/10.1088/1361-6560/ac944c
- J. Baran, …, A. Rucinski et al. Feasibility of the J-PET to monitor range of therapeutic proton beams under review in Phys. Med. Biol. 2023
- K. Brzeziński, …, A. Rucinski et al. Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study under review in Phys. Med. Biol. 2023
- A. Rucinski, …, et al. Plastic scintillator based PET detector technique for proton therapy range monitoring. A Monte Carlo study. 2018 IEEE Nuclear Science Symposium and Medical Imaging Conference Proceedings (NSS/MIC) 2018 pp. 1-4, https://doi.org/10.1109/NSSMIC.2018.8824654
- J. Baran, …, A. Rucinski et al. Studies of J-PET detector to monitor range uncertainty in proton therapy, Proc. of the 2019 IEEE Nuclear Science Symposium and Medical Imaging Conference, Manchester, UK, 2019 9059793 https://doi.org/10.1109/NSS/MIC42101.2019.9059793
- A. Ruciński, …, et al., Investigations On Physical And Biological Range Uncertainties In Krakow Proton Beam Therapy Centre, Acta Phys. Pol. B, 2020 51:9-16, https://doi.org/10.5506/APhysPolB.51.9