Treatments delivered by proton therapy are affected by uncertainties on the range of the beam within the patient, requiring medical physicists to add safety margins on the penetration depth of the beam. 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 feasibility, development and test of a new concept of prompt gamma camera using a slit collimator to obtain a one-dimensional projection of the beam path on a scintillation detector. This concept was optimized, using the Monte Carlo code MCNPX version 2.5.0, to select high energy photons correlated with the beam range and detect them with both high statistics and sufficient spatial resolution. To validate the Monte Carlo model, spectrometry measurements of secondary particles emitted by a PMMA target during proton irradiation at 160 MeV were realized. An excellent agreement with the simulations was observed when using subtraction methods to isolate the gammas in direct incidence. A first prototype slit camera using the HiCam gamma detector was consequently prepared and tested successfully at 100 and 160 MeV beam energies. Results confirmed the potential of this concept for real-time range monitoring with millimetre accuracy in pencil beam scanning mode for typical clinical conditions. If we neglect electronic dead times and rejection of detected events, the current solution with its collimator at 15 cm from the beam axis can achieve a 1-2 mm standard deviation on range estimation in a homogeneous PMMA target for numbers of protons that correspond to doses in water at the Bragg peak as low as 15 cGy at 100 MeV and 25 cGy at 160 MeV assuming pencil beams with a Gaussian profile of 5 mm sigma at target entrance.

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.

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In this work, we present experimental results of a prompt gamma camera for real-time proton beam range verification. The detection system features a pixelated Cerium doped lutetium based scintillation crystal, coupled to Silicon PhotoMultiplier arrays, read out by dedicated electronics. The prompt gamma camera uses a knife-edge slit collimator to produce a 1D projection of the beam path in the target on the scintillation detector. We designed the detector to provide high counting statistics and high photo-detection efficiency for prompt gamma rays of several MeV. The slit design favours the counting statistics and could be advantageous in terms of simplicity, reduced cost and limited footprint. We present the description of the realized gamma camera, as well as the results of the characterization of the camera itself in terms of imaging performance. We also present the results of experiments in which a polymethyl methacrylate phantom was irradiated with proton pencil beams in a proton therapy center. A tungsten slit collimator was used and prompt gamma rays were acquired in the 3-6 MeV energy range. The acquisitions were performed with the beam operated at 100 MeV, 160 MeV and 230 MeV, with beam currents at the nozzle exit of several nA. Measured prompt gamma profiles are consistent with the simulations and we reached a precision (2σ) in shift retrieval of 4 mm with 0.5 × 10(8), 1.4 × 10(8) and 3.4 × 10(8) protons at 100, 160 and 230 MeV, respectively. We conclude that the acquisition of prompt gamma profiles for in vivo range verification of proton beam with the developed gamma camera and a slit collimator is feasible in clinical conditions. The compact design of the camera allows its integration in a proton therapy treatment room and further studies will be undertaken to validate the use of this detection system during treatment of real patients.

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.

On-line image guidance using magnetic resonance (MR) imaging is expected to improve the targeting accuracy of proton therapy. However, to date no combined system exists. In this study, for the first time a low-field open MR scanner was integrated with a static proton research beam line to test the feasibility of simultaneous irradiation and imaging. The field-of-view of the MR scanner was aligned with the beam by taking into account the Lorentz force induced beam deflection. Various imaging sequences for extremities were performed on a healthy volunteer and on a patient with a soft-tissue sarcoma of the upper arm, both with the proton beam line switched off. T1-weighted spin echo images of a tissue-mimicking phantom were acquired without beam, with energised beam line magnets and during proton irradiation. Beam profiles were acquired for the MR scanner’s static magnetic field alone and in combination with the dynamic gradient fields during the acquisition of different imaging sequences. It was shown that MR imaging is feasible in the electromagnetically contaminated environment of a proton therapy facility. The observed quality of the anatomical MR images was rated to be sufficient for target volume definition and positioning. The tissue-mimicking phantom showed no visible beam-induced image degradation. The beam profiles depicted no influence due to the dynamic gradient fields of the imaging sequences. This study proves that simultaneous irradiation and in-beam MR imaging is technically feasible with a low-field MR scanner integrated with a static proton research beam line.

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.

Proton and ion beam therapies become increasingly relevant in radiation therapy. To fully exploit the potential of this irradiation technique and to achieve maximum target volume conformality, the verification of particle ranges is highly desirable. Many research activities focus on the measurement of the spatial distributions of prompt gamma rays emitted during irradiation. A passively collimating knife-edge slit camera is a promising option to perform such measurements. In former publications, the feasibility of accurate detection of proton range shifts in homogeneous targets could be shown with such a camera. We present slit camera measurements of prompt gamma depth profiles in inhomogeneous targets. From real treatment plans and their underlying CTs, representative beam paths are selected and assembled as one-dimensional inhomogeneous targets built from tissue equivalent materials. These phantoms have been irradiated with monoenergetic proton pencil beams. The accuracy of range deviation estimation as well as the detectability of range shifts is investigated in different scenarios. In most cases, range deviations can be detected within less than 2 mm. In close vicinity to low-density regions, range detection is challenging. In particular, a minimum beam penetration depth of 7 mm beyond a cavity is required for reliable detection of a cavity filling with the present setup. Dedicated data post-processing methods may be capable of overcoming this limitation.