Range assessment in particle therapy based on prompt gamma-ray timing measurements

Proton and ion beams open up new vistas for the curative treatment of tumors, but adequate technologies for monitoring the compliance of dose delivery with treatment plans in real time are still missing. Range assessment, meaning the monitoring of therapy-particle ranges in tissue during dose delivery (treatment), is a continuous challenge considered a key for tapping the full potential of particle therapies. In this context the paper introduces an unconventional concept of range assessment by prompt-gamma timing (PGT), which is based on an elementary physical effect not considered so far: therapy particles penetrating tissue move very fast, but still need a finite transit time-about 1-2 ns in case of protons with a 5-20 cm range-from entering the patient's body until stopping in the target volume. The transit time increases with the particle range. This causes measurable effects in PGT spectra, usable for range verification. The concept was verified by proton irradiation experiments at the AGOR cyclotron, KVI-CART, University of Groningen. Based on the presented kinematical relations, we describe model calculations that very precisely reproduce the experimental results. As the clinical treatment conditions entail measurement constraints (e.g. limited treatment time), we propose a setup, based on clinical irradiation conditions, capable of determining proton range deviations within a few seconds of irradiation, thus allowing for a fast safety survey. Range variations of 2 mm are expected to be clearly detectable

A hybrid multi-particle approach to range assessment-based treatment verification in particle therapy

Particle therapy (PT) used for cancer treatment can spare healthy tissue and reduce treatment toxicity. However, full exploitation of the dosimetric advantages of PT is not yet possible due to range uncertainties, warranting development of range-monitoring techniques. This study proposes a novel range-monitoring technique introducing the yet unexplored concept of simultaneous detection and imaging of fast neutrons and prompt-gamma rays produced in beam-tissue interactions. A quasimonolithic organic detector array is proposed, and its feasibility for detecting range shifts in the context of proton therapy is explored through Monte Carlo simulations of realistic patient models and detector resolution efects. The results indicate that range shifts of 1 mm can be detected at relatively low proton intensities (22.30(13) × 107 protons/spot) when spatial information obtained through imaging of both particle species are used simultaneously. This study lays the foundation for multiparticle detection and imaging systems in the context of range verifcation in PTpublishedVersio

Experimental data for investigating proton bunch monitors for clinical translation of prompt gamma-ray timing

The dataset contains the data reported on https://www.hzdr.de/publications/Publ-39073 where 2 proton bunch monitors (PBMs), namely the diamond detector and the cyclotron monitoring signal Uphi, are established, characterized, and applied for correcting the prompt gamma-ray timing (PGT) data. Experimental setup, irradiation modalities, data acquisition, and data pre- and postprocessing are described there. The process is summarized in the following: Experimental setup: A homogeneous cylindrical PMMA phantom was irradiated with a proton beam. Two sets of measurements were considered: S1) measurements at the horizontal fixed beamline with the control of the beam time structure and current. These data establish the relation between the investigated PBMs and calibrate them to the scattering setup that provides the proton bunch arrival time in the experimental room. The phantom was irradiated with 7 different proton energies Ep = {70, 90, 110, 130, 160, 190, 224} MeV. For each Ep, 3 irradiation modalities were applied: CW-mode represented the continuous beam lasting for 30 s, the beam current Ibeam = 2 nA for all Ep excluding 70 MeV (for 70 MeV, Ibeam = 0.5 nA); Plan I represented a clinically realistic plan with a spot duration of 4 ms and a spot repetition time of 7 ms. The beam current Ibeam = 1 nA for all Ep excluding 70 MeV (for 70 MeV, Ibeam = 0.5 nA); Plan II aimed to reproduce the measurements of Werner et al. (2019) in Phys. Med. Biol. 64 105023, 20pp (https://doi.org/10.1088/1361-6560/ab176d). For that, the spot duration was set to 69 ms, and the repetition time was 72 ms. The beam current Ibeam = 1 nA for all Ep excluding 70 MeV (for 70 MeV, Ibeam = 0.5 nA). S2) measurements at the pencil beam scanning (PBS) beamline were similar to those at the clinical beam delivery nozzle. The PBS beamline delivers the beam as spots of given intensity (expressed in MU), (x,y)-coordinates, and energy (corresponds to the penetration depth or z-coordinate). These data comprise data from the PGT detector and PBMs and are used to correct the PGT data employing the investigated PBMs. The phantom was irradiated with 8 different proton energies Ep = {70, 90, 110, 130, 162, 180, 200, 220} MeV. For every energy, 2 spot intensities were considered: 0.1 MU per 1 spot (~1e7 protons) and 1 MU per 1 spot (~1e8 protons). For Ep = 162 MeV, an additional spot intensity of 10 MU per 1 spot (~1e9 protons) was applied to reproduce the measurements of Werner et al. (2019) in Phys. Med. Biol. 64 105023, 20pp (https://doi.org/10.1088/1361-6560/ab176d). Data preprocessing: The raw data of each measurement were converted from the binary list-mode format to ROOT TTrees. The data were corrected for the photomultiplier gain drift, and digitalization time non-linearities, and the integral signal was converted into deposited energy. For the measurements at the fixed beamline, the coincidence analysis was applied additionally for non-PBM detectors. The data were assigned to individual corresponding spots for the PBS beamline measurements. Data structure: The ROOT files are named u100-p00XX-yyyy-mm-dd_HH.MM.SS+TZ.root where p00XX is the detector’s number, yyyy-mm-dd_HH.MM.SS is the time of the measurement, and TZ is the time zone. Here, p0012 and p0019 mean scintillating detectors that were used both at the fixed beamline, and only detector p0012 was used for PGT measurements at the PBS beamline. P0015 is the diamond detector, and p0017 contains data of the Uphi signal. In general, the data structure inside the ROOT files is different depending on the purpose of the detector. However, there are some general includes: data (TTree) contains list-mode data which comprises uncorrected data: before corrections and calibrations steps; corrected data: after correcations and calibrations steps; meta (TTree) is a measurement metadata (applied detector voltage, the start time of the measurements, etc.); histograms is a directory with selected example histograms (uncorrected); analysis is a directory with histograms with corrected data used for the analysis. For further questions, please refer to the contact persons stated above

Prompt gamma spectroscopy for range control with CeBr3

The ultimate goal of radiotherapy using external beams is to maximize the dose delivered to the tumor while minimizing the radiation given to surrounding healthy critical organs. Prompt Gamma Spectroscopy (PGS) has been proposed for range control of particle beams along with the determination of the elemental composition of irradiated tissues. We aim at developing a PGS system for the German Cancer Research Center – DKFZ that takes advantage of the superior selectivity of Helium and Carbon beams accelerated at the Heidelberg Ion-Beam Therapy Center. Preliminary tests with protons accelerated with an IBA C230 cyclotron located at the Universitäts Protonen Therapie Dresden were performed at OncoRay – National Center for Radiation Re-search in Oncology. We present results obtained with a PGS system composed of CeBr3 detectors (Ø 2’’ × 2’’) and (Ø 1.5’’ × 3’’) coupled to a Hamamatsu R13089 photomulti-plier tube and plugged to a Target U100 Spectrometer. Such system provides accurate time-of-flight measurements to increase the signal-to-noise ratio relative to neutron-induced background. First measurements resulted from the irradiation of PMMA and water phantoms, and graphite and aluminum bricks. Several PG energy lines ranging from 0.511 MeV up to 8 MeV were identified and compared with reference re-sults. Two further experiments consisted in irradiating PMMA phantoms in a slit- and semi-collimated configuration with mono-energetic proton beams of 165 MeV and 224 MeV, respectively. Results acquired by means of trans-versal PGS at different phantom depths, ranging from 6 cm before the Bragg peak (BP) to 3.5 cm beyond the BP in 5 mm steps with a 1 cm slit collimation (tungsten) showed a slight decrease of PG yields after the BP. Similar measurements with a semi-opened collimation configuration demonstrated a steeper decrease of PG yields after the BP