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.

https://iopscience.iop.org/article/10.1088/0031-9155/57/11/3371/pdf

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

Charged particle therapy has been largely driven and influenced by nuclear physics. The increase in energy deposition density along the ion path in the body allows reducing the dose to normal tissues during radiotherapy compared to photons. Clinical results of particle therapy support the physical rationale for this treatment, but the method remains controversial because of the high cost and of the lack of comparative clinical trials proving the benefit compared to x-rays. Research in applied nuclear physics, including nuclear interactions, dosimetry, image guidance, range verification, novel accelerators and beam delivery technologies, can significantly improve the clinical outcome in particle therapy. Measurements of fragmentation cross-sections, including those for the production of positron-emitting fragments, and attenuation curves are needed for tuning Monte Carlo codes, whose use in clinical environments is rapidly increasing thanks to fast calculation methods. Existing cross sections and codes are indeed not very accurate in the energy and target regions of interest for particle therapy. These measurements are especially urgent for new ions to be used in therapy, such as helium. Furthermore, nuclear physics hardware developments are frequently finding applications in ion therapy due to similar requirements concerning sensors and real-time data processing. In this review we will briefly describe the physics bases, and concentrate on the open issues.

https://iopscience.iop.org/article/10.1088/0034-4885/79/9/096702/pdf

Nuclear physics in particle therapy: a review.

Secondary radiation emission induced by nuclear reactions is correlated to the path of ions in matter. Therefore, such penetrating radiation can be used for in vivo control of hadrontherapy treatments, for which the primary beam is absorbed inside the patient. Among secondary radiations, prompt-gamma rays were proposed for real-time verification of ion range. Such a verification is a desired condition to reduce uncertainties in treatment planning. For more than a decade, efforts have been undertaken worldwide to promote prompt-gamma-based devices to be used in clinical conditions. Dedicated cameras are necessary to overcome the challenges of a broad- and high-energy distribution, a large background, high instantaneous count rates, and compatibility constraints with patient irradiation. Several types of prompt-gamma imaging devices have been proposed, that are either physically-collimated or electronically collimated (Compton cameras). Clinical tests are now undergoing. Meanwhile, other methods than direct prompt-gamma imaging were proposed, that are based on specific counting using either time-of-flight or photon energy measurements. In the present article, we make a review and discuss the state of the art for all techniques using prompt-gamma detection to improve the quality assurance in hadrontherapy.

Prompt-gamma monitoring in hadrontherapy: A review

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.

/pdf/range-assessment-in-particle-therapy-based-on-prompt-g-ray-kbsup1b3i9.pdf

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

Exploitation of the full potential offered by ion beams in clinical practice is still hampered by several sources of treatment uncertainties, particularly related to the limitations of our ability to locate the position of the Bragg peak in the tumor. To this end, several efforts are ongoing to improve the characterization of patient position, anatomy, and tissue stopping power properties prior to treatment as well as to enable in vivo verification of the actual dose delivery, or at least beam range, during or shortly after treatment. This contribution critically reviews methods under development or clinical testing for verification of ion therapy, based on pretreatment range and tissue probing as well as the detection of secondary emissions or physiological changes during and after treatment, trying to disentangle approaches of general applicability from those more specific to certain anatomical locations. Moreover, it discusses future directions, which could benefit from an integration of multiple modalities or address novel exploitation of the measurable signals for biologically adapted therapy.

/pdf/in-vivo-range-verification-in-particle-therapy-zkjoz3hxmx.pdf

In vivo range verification in particle therapy.

We investigate, by means of Geant4 simulations, a real-time method to control the position of the Bragg peak during ion therapy, based on a Compton camera in combination with a beam tagging device (hodoscope) in order to detect the prompt gamma emitted during nuclear fragmentation The proposed set-up consists of a stack of 2 mm thick silicon strip detectors and a LYSO absorber detector The γ emission points are reconstructed analytically by intersecting the ion trajectories given by the beam hodoscope and the Compton cones given by the camera The camera response to a polychromatic point source in air is analyzed with regard to both spatial resolution and detection efficiency Various geometrical configurations of the camera have been tested In the proposed configuration, for a typical polychromatic photon point source, the spatial resolution of the camera is about 83 mm FWHM and the detection efficiency 25×10−4 (reconstructable photons/emitted photons in 4 π ) Finally, the clinical applicability of our system is considered and possible starting points for further developments of a prototype are discussed

Design of a Compton camera for 3D prompt-γ imaging during ion beam therapy

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.

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

Longitudinal prompt-gamma ray profiles have been measured with a multi-slit multi-detector configuration at a 75 MeV/u 13C beam and with a PMMA target. Selections in time-of-flight and energy have been applied in order to discriminate prompt-gamma rays produced in the target from background events. The ion ranges which have been extracted from each individual detector module agree amongst each other and are consistent with theoretical expectations. In a separate dedicated experiment with 200 MeV/u 12C ions the fraction of inter-detector scattering has been determined to be on the 10%-level via a combination of experimental results and simulations. At the same experiment different collimator configurations have been tested and the shielding properties of tungsten and lead for prompt-gamma rays have been measured.

/pdf/collimated-prompt-gamma-tof-measurements-with-multi-slit-1r5609xnfr.pdf

F. Roellinghoff

Papers

Design of a Compton camera for 3D prompt-γ imaging during ion beam therapy

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

Collimated prompt gamma TOF measurements with multi-slit multi-detector configurations