D. Prieels

Prompt gamma imaging with a slit camera for real-time range control in proton therapy.

Treatments delivered by proton therapy are affected by uncertainties on the range of the beam within the patient. To reduce these margins and deliver safer treatments, different projects are currently investigating real-time range control by imaging prompt gammas emitted along the proton tracks in the patient. This study reports on the development and test of a prompt gamma camera using a slit collimator to obtain a 1-dimensional projection of the beam path on a scintillator detector. A first prototype slit camera using the HICAM gamma detector, originally developed for low-energy gamma-ray imaging in nuclear medicine and modified for this purpose, was tested successfully up to 230 MeV beam energy. Results now confirm the potential of this concept for real-time range monitoring with millimeter accuracy in pencil beam scanning mode for the whole range of clinical energies. With the experience gained, a new prototype is under study for clinical beam currents. In this work, we present both the profiles obtained at 230 MeV using HICAM and the description of the new gamma camera prototype design.

First clinical application of a prompt gamma based in vivo proton range verification system

BACKGROUND AND PURPOSE To improve precision of particle therapy, in vivo range verification is highly desirable. Methods based on prompt gamma rays emitted during treatment seem promising but have not yet been applied clinically. Here we report on the worldwide first clinical application of prompt gamma imaging (PGI) based range verification. MATERIAL AND METHODS A prototype of a knife-edge shaped slit camera was used to measure the prompt gamma ray depth distribution during a proton treatment of a head and neck tumor for seven consecutive fractions. Inter-fractional variations of the prompt gamma profile were evaluated. For three fractions, in-room control CTs were acquired and evaluated for dose relevant changes. RESULTS The measurement of PGI profiles during proton treatment was successful. Based on the PGI information, inter-fractional global range variations were in the range of ±2 mm for all evaluated fractions. This is in agreement with the control CT evaluation showing negligible range variations of about 1.5mm. CONCLUSIONS For the first time, range verification based on prompt gamma imaging was applied for a clinical proton treatment. With the translation from basic physics experiments into clinical operation, the potential to improve the precision of particle therapy with this technique has increased considerably.

First test of the prompt gamma ray timing method with heterogeneous targets at a clinical proton therapy facility.

Ion beam therapy promises enhanced tumour coverage compared to conventional radiotherapy, but particle range uncertainties significantly blunt the achievable precision. Experimental tools for range verification in real-time are not yet available in clinical routine. The prompt gamma ray timing method has been recently proposed as an alternative to collimated imaging systems. The detection times of prompt gamma rays encode essential information about the depth-dose profile thanks to the measurable transit time of ions through matter. In a collaboration between OncoRay, Helmholtz-Zentrum Dresden-Rossendorf and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen, Germany) with several detectors and phantoms is performed. The robustness of the method against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterized for different proton energies. For a beam spot with a hundred million protons and a single detector, range differences of 5 mm in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to 2 mm are detectable. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype. In conclusion, the experimental results highlight the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry.

Real-time proton beam range monitoring by means of prompt-gamma detection with a collimated camera

Prompt-gamma profile was measured at WPE-Essen using 160 MeV protons impinging a movable PMMA target. A single collimated detector was used with time-of-flight (TOF) to reduce the background due to neutrons. The target entrance rise and the Bragg peak falloff retrieval precision was determined as a function of incident proton number by a fitting procedure using independent data sets. Assuming improved sensitivity of this camera design by using a greater number of detectors, retrieval precisions of 1 to 2 mm (rms) are expected for a clinical pencil beam. TOF improves the contrast-to-noise ratio and the performance of the method significantly.

Effect of tissue heterogeneity on an in vivo range verification technique for proton therapy

It was proposed recently that time-resolved dose measurements during proton therapy treatment by passively scattered beams may be used for in vivo range verification. The method was shown to work accurately in a water tank. In this paper, we further evaluated the potential of the method for more clinically relevant situations where proton beams must pass through regions with significant tissue heterogeneities. Specifically, we considered prostate treatment where the use of anterior or anterior- oblique fields was recently proposed in order to reduce rectal dose by taking advantage of the sharp distal fall-off of the Bragg peak. These beam portals pass through various parts of pubic bone and potential air cavities in the bladder and bowels. Using blocks of materials with densities equivalent to bone, air, etc, arranged in the water tank in relevant configurations, we tested the robustness of the method against range shifting and range mixing. In the former, the beam range is changed uniformly by changes in tissue density in the beam path, while in the latter, variations in tissue heterogeneities across the beam cross section causes the mixing of beam energies downstream, as often occurs when the beam travels along the interface of materials with significantly different densities. We demonstrated that in the region of interest, the method can measure water-equivalent path length with accuracy better than ±0.5 mm for pure range shifting and still reasonable accuracy for range mixing between close beam energies. In situations with range mixing between significantly different beam energies, the dose rate profiles may be simulated for verifying the beam range. We also found that the above performances can be obtained with very small amount of dose (<0.5 cGy), if silicon diodes are used as detectors. This makes the method suitable for in vivo range verification prior to each treatment delivery.

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron

PURPOSE To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. METHODS An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. RESULTS The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. CONCLUSIONS The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.

The IBA state-of-the-art proton therapy system, performances and recent results

In recent years IBA has continued its development of state-of-the-art systems for Proton Therapy. While the machine performance at the NPTC is such that all clinical specifications are met, IBA has continued to improve the proposed equipment to set even higher standards. Improvements in the ion source control, gantries, and patient alignment systems will be addressed in the oral presentation and the first results obtained with the Pencil Beam Scanning algorithm will be presented.

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.

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera.

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ). For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2-5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained. With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements.

PURPOSE In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. METHODS An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. RESULTS Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. CONCLUSIONS Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.