Novel Bragg peak characterization method using proton flux measurements on plastic scintillators.

\textit{Objective}. Bragg peak measurements play a key role in the beam quality assurance in proton therapy. Used as base data for the treatment planning softwares, the accuracy of the data is crucial when defining the range of the protons in the patient, for the sparing of healthy tissue but also for a correct volumetric dose distribution. \textit{Approach} In this paper a protocol to reconstruct a Pristine Bragg Peak exploring the direct correlation between the particle flux and the dose deposited by particles is presented. Proton flux measurements at the HollandPTC and FLUKA Monte Carlo simulations are used for this purpose. This new protocol is applicable to plastic scintillator detectors developed for Quality Assurance applications. In order to obtain the Bragg curve using a plastic fiber detector, a PMMA phantom with a decoupled and moveable stepper was designed. The step phantom allows to change the depth of material in front of the fiber detector during irradiations. The Pristine Bragg Peak reconstruction protocol uses the measured flux of particles at each position and multiplies it by the average dose obtained from the Monte Carlo simulation at each position. \textit{Main Result} The results show that with this protocol it is possible to reconstruct the Bragg Peak with an accuracy of about 470 µm, which is in accordance with the tolerances set by the AAPM. Improvements to the protocol and further applications are also discussed. \textit{Significance} It has the advantage to be able to overcome the quenching problem of scintillators in the high ionization density region of the Bragg peak. .

In-beam PET measurements of biological half-lives of 12C irradiation induced beta+-activity.

One of the long-standing problems in carbon-ion therapy is the monitoring of the treatment, i.e. of the delivered dose to a given tissue volume within the patient. Over the last 8 years, in-beam positron emission tomography (PET) has been used at the experimental carbon ion treatment facility at the Gesellschaft fur Schwerionenforschung (GSI) Darmstadt and has become a valuable quality assurance tool. In order to determine and evaluate the correct delivery of the patient dose, a simulation of the positron emitter distribution has been compared to the measurement. One particular effect is the blurring as well as the reduction of the measured activity distribution via washout. The objective of this study is the investigation of tissue dependent effective half-lives from patient data. We find no significant dependence of the effective half-life on the Hounsfield unit but on the local dose. The biological half-life within the high dose region is longer than in the low dose region. Furthermore, the influence of the overall treatment time on the kinetics of the positron emitter is reported. There are indications for a metabolic response of the tissue on the irradiation. Taking into account the biological half-life in the simulation leads to an improvement of the quality of the PET-images in some cases.

Simulation of proton range monitoring in an anthropomorphic phantom using multi-slat collimators and time-of-flight detection of prompt-gamma quanta.

Prompt-gamma (PG) imaging has the potential for monitoring proton therapy in real time. Different approaches are investigated. We focus on developing multi-slat collimators to image PG quanta, aiming at optimizing collimator performance to detect deviations in treatment delivery. We investigated six different multi-slat configurations, which have either optimal (analytical) intrinsic spatial resolution at fixed efficiency, or otherwise; at different distances from the proton pencil-beam axis (15 cm-35 cm). We used Geant4 to simulate irradiations of the head (energy: 130 MeV) and pelvis (200 MeV) of an anthropomorphic phantom, with and without physiologic/morphologic or setup changes of clinical dosimetric relevance. The particles escaping the phantom were transported through each of these multi-slat configurations and the gamma counts profiles were recorded at the collimator exit. Median filtering was applied to the registered PG-profiles to mitigate the effects of septa shadowing and statistical fluctuations. Time-of-flight discrimination was used to enhance the signal-to-background ratio, which appeared crucial for 200 MeV irradiations. Visual detection of the artificially introduced changes was possible by comparing the PG to the depth-dose profiles. Moreover, 2 mm range shifts could be detected in the head irradiation case using a simple linear regression fit to the falloff of the PG-profile. The influence of changes in complex, patient-like dose distributions on the PG-profiles obtained with multi-slat collimation is first studied in this work, which further gives insight on collimator design optimization and highlights its potential and simplicity for detecting proton treatment deviations over a wide range of Bragg peak positions.

Direct time-of-flight for quantitative, real-time in-beam PET: a concept and feasibility study.

We extrapolate the impact of recent detector and scintillator developments, enabling sub-nanosecond coincidence timing resolution (tau), onto in-beam positron emission tomography (in-beam PET) for monitoring charged-hadron radiation therapy. For tau < or = 200 ps full width at half maximum, the information given by the time-of-flight (TOF) difference between the two opposing gamma-rays enables shift-variant, artefact-free in-beam tomographic imaging by means of limited-angle, dual-head detectors. We present the corresponding fast, TOF-based and backprojection-free, 3D reconstruction algorithm that, coupled with a real-time data acquisition and a fast detector encoding scheme, allows the sampled beta+-activity to be visualized in the object during the course of the irradiation. Despite the very low statistics scenario typical of in-beam PET, real-treatment simulations show that in-beam TOF-PET enables high-precision images to be obtained in real-time, either with closed-ring or with fixed, dual-head in-beam TOF-PET systems. The latter greatly alleviates the installation of in-beam PET at radiotherapeutic sites.

On the detector arrangement for in-beam PET for hadron therapy monitoring.

In-beam positron emission tomography (in-beam PET) is currently the only method for an in situ monitoring of highly tumour-conformed charged hadron therapy. At the experimental carbon ion tumour therapy facility, running at the Gesellschaft für Schwerionenforschung, Darmstadt, Germany, all treatments have been monitored by means of a specially adapted dual-head PET scanner. The positive clinical impact of this project triggered the construction of a hospital-based hadron therapy facility, with in-beam PET expected to monitor more delicate radiotherapeutic situations. Therefore, we have studied possible in-beam PET improvements by optimizing the arrangement of the gamma-ray detectors. For this, a fully 3D, rebinning-free, maximum likelihood expectation maximization algorithm applicable to several closed-ring or dual-head tomographs has been developed. The analysis of beta(+)-activity distributions simulated from real-treatment situations and detected with several detector arrangements allows us to conclude that a dual-head tomograph with narrow gaps yields in-beam PET images with sufficient quality for monitoring head and neck treatments. For monitoring larger irradiation fields, e.g. treatments in the pelvis region, a closed-ring tomograph was seen to be highly desirable. Finally, a study of the space availability for patient and bed, tomograph and beam portal proves the implementation of a closed-ring detector arrangement for in-beam PET to be feasible.

Time-resolved imaging of prompt-gamma rays for proton range verification using a knife-edge slit camera based on digital photon counters.

Proton range monitoring may facilitate online adaptive proton therapy and improve treatment outcomes. Imaging of proton-induced prompt gamma (PG) rays using a knife-edge slit collimator is currently under investigation as a potential tool for real-time proton range monitoring. A major challenge in collimated PG imaging is the suppression of neutron-induced background counts. In this work, we present an initial performance test of two knife-edge slit camera prototypes based on arrays of digital photon counters (DPCs). PG profiles emitted from a PMMA target upon irradiation with a 160 MeV proton pencil beams (about 6.5 × 10(9) protons delivered in total) were measured using detector modules equipped with four DPC arrays coupled to BGO or LYSO : Ce crystal matrices. The knife-edge slit collimator and detector module were placed at 15 cm and 30 cm from the beam axis, respectively, in all cases. The use of LYSO : Ce enabled time-of-flight (TOF) rejection of background events, by synchronizing the DPC readout electronics with the 106 MHz radiofrequency signal of the cyclotron. The signal-to-background (S/B) ratio of 1.6 obtained with a 1.5 ns TOF window and a 3 MeV-7 MeV energy window was about 3 times higher than that obtained with the same detector module without TOF discrimination and 2 times higher than the S/B ratio obtained with the BGO module. Even 1 mm shifts of the Bragg peak position translated into clear and consistent shifts of the PG profile if TOF discrimination was applied, for a total number of protons as low as about 6.5 × 10(8) and a detector surface of 6.6 cm × 6.6 cm.

Optimization of multiple coils immersed in a conducting liquid for half-hemisphere or whole-brain deep transcranial magnetic stimulation: a simulation study.

Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its wider use in the treatment of several neurologic diseases has been hindered by its inability to stimulate deep-brain regions. This is mainly due to the physical limiting effect arising from the presence of surface discontinuities, particularly between the scalp and air. Here, we present the optimization of a system of large multiple coils for whole-brain and half-hemisphere deep TMS, termed orthogonal configuration. COMSOL(®)-based simulations show that the system is capable of reaching the very center of a spherical brain phantom with 58% induction relative to surface maximum. Such penetration capability surpasses to the best of our knowledge that of existing state of the art TMS systems. This induction capability strongly relies on the immersion of the stimulating coils and part of the head of the patient in a conducting liquid (e.g. simple saline solution). We show the impact of the presence of this surrounding conducting liquid by comparing the performance of our system with and without such liquid. In addition, we also compare the performance of the proposed coil with that of a circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its whole-brain stimulation capability (e.g. potentially useful for prophylaxis of epileptic patients) the system is also able to stimulate mainly one brain hemisphere, which may be useful in stroke rehabilitation, among other applications.

Time-of-flight neutron rejection to improve prompt gamma imaging for proton range verification: a simulation study.

Therapeutic proton and heavier ion beams generate prompt gamma photons that may escape from the patient. In principle, this allows for real-time, in situ monitoring of the treatment delivery, in particular, the hadron range within the patient, by imaging the emitted prompt gamma rays. Unfortunately, the neutrons simultaneously created with the prompt photons create a background that may obscure the prompt gamma signal. To enhance the accuracy of proton dose verification by prompt gamma imaging, we therefore propose a time-of-flight (TOF) technique to reject this neutron background, involving a shifting time window to account for the propagation of the protons through the patient. Time-resolved Monte Carlo simulations of the generation and transport of prompt gamma photons and neutrons upon irradiation of a PMMA phantom with 100, 150 and 200 MeV protons were performed using Geant4 (version 9.2.p02) and MCNPX (version 2.7.D). The influence of angular collimation and TOF selection on the prompt gamma and neutron longitudinal profiles is studied. Furthermore, the implications of the proton beam microstructure (characterized by the proton bunch width and repetition period) are investigated. The application of a shifting TOF window having a width of ΔTOF(z) = 1.0 ns appears to reduce the neutron background by more than 99%. Subsequent application of an energy threshold does not appear to sharpen the distal falloff of the prompt gamma profile but reduces the tail that is observed beyond the proton range. Investigations of the influence of the beam time structure show that TOF rejection of the neutron background is expected to be effective for typical therapeutic proton cyclotrons.

On the effectiveness of ion range determination from in-beam PET data.

At present, in-beam positron emission tomography (PET) is the only method for in vivo and in situ range verification in ion therapy. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH (GSI) Darmstadt, Germany, a unique in-beam PET installation has been operated from 1997 until the shut down of the carbon ion therapy facility in 2008. Therapeutic irradiation by means of (12)C ion beams of more than 400 patients have been monitored. In this paper a first quantitative study on the accuracy of the in-beam PET method to detect range deviations between planned and applied treatment in clinically relevant situations using simulations based on clinical data is presented. Patient treatment plans were used for performing simulations of positron emitter distributions. For each patient a range difference of + or - 6 mm in water was applied and compared to simulations without any changes. The comparisons were performed manually by six experienced evaluators for data of 81 patients. The number of patients required for the study was calculated using the outcome of a pilot study. The results indicate a sensitivity of (91 + or - 3)% and a specificity of (96 + or - 2)% for detecting an overrange, a reduced range is recognized with a sensitivity of (92 + or - 3)% and a specificity of (96 + or - 2)%. The positive and the negative predictive value of this method are 94% and 87%, respectively. The interobserver coefficient of variation is between 3 and 8%. The in-beam PET method demonstrated a high sensitivity and specificity for the detection of range deviations. As the range is a most indicative factor of deviations in the dose delivery, the promising results shown in this paper confirm the in-beam PET method as an appropriate tool for monitoring ion therapy.