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

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.

Dual energy CT in radiotherapy: Current applications and future outlook

The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents. The prototype CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data (2D) images of the PG emission were reconstructed. (1D) profiles were extracted from the PG images and compared to measured depth dose curves of the delivered proton pencil beams. The CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV proton beams at clinical beam currents. 2D images of the PG emission were reconstructed for single 150 MeV proton pencil beams as well as for a 5   ×   5 cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP) range were detectable on the 2D images. 1D profiles extracted from the PG images show that the distal falloff of the PG emission profile lined up well with the distal BP falloff. Shifts as small as 3 mm in the beam range could be detected from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the current CC prototype, a dose of 400 cGy was required to acquire adequate PG signal for 2D PG image reconstruction. It was possible to measure PG interactions with our prototype CC during delivery of proton pencil beams at clinical dose rates. Images of the PG emission could be reconstructed and shifts in the BP range were detectable. Therefore PGI with a CC for in vivo range verification during proton treatment delivery is feasible. However, improvements in the prototype CC detection efficiency and reconstruction algorithms are necessary to make it a clinically viable PGI system.

https://iopscience.iop.org/article/10.1088/0031-9155/60/18/7085/pdf

Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification.

It is recognized that the use of a single plan calculated on an image acquired some time before the treatment is generally insufficient to accurately represent the daily dose to the target and to the organs at risk. This is particularly true for protons, due to the physical finite range. Although this characteristic enables the generation of steep dose gradients, which is essential for highly conformal radiotherapy, it also tightens the dependency of the delivered dose to the range accuracy. In particular, the use of an outdated patient anatomy is one of the most significant sources of range inaccuracy, thus affecting the quality of the planned dose distribution. A plan should be ideally adapted as soon as anatomical variations occur, ideally online. In this review, we describe in detail the different steps of the adaptive workflow and discuss the challenges and corresponding state-of-the art developments in particular for an online adaptive strategy.

/pdf/online-daily-adaptive-proton-therapy-24v4iz0tbo.pdf

Online daily adaptive proton therapy.

Purpose:
Range verification in ion beam therapy relies to date on nuclear imaging techniques which require complex and costly detector systems. A different approach is the detection of thermoacoustic signals that are generated due to localized energy loss of ion beams in tissue (ionoacoustics). Aim of this work was to study experimentally the achievable position resolution of ionoacoustics under idealized conditions using high frequency ultrasonic transducers and a specifically selected probing beam.
Methods:
A water phantom was irradiated by a pulsed 20 MeV proton beam with varying pulse intensity and length. The acoustic signal of single proton pulses was measured by different PZT-based ultrasound detectors (3.5 and 10 MHz central frequencies). The proton
dose distribution in water was calculated by Geant4 and used as input for simulation of the generated acoustic wave by the matlab toolbox k-WAVE.
Results:
In measurements from this study, a clear signal of the Bragg peak was observed for an energy deposition as low as 1012 eV. The signal amplitude showed a linear increase with particle number per pulse and thus, dose. Bragg peak position measurements were reproducible within ±30 μm and agreed with Geant4 simulations to better than 100 μm. The ionoacoustic signal pattern allowed for a detailed analysis of the Bragg peak and could be well reproduced by k-WAVE simulations.
Conclusions:
The authors have studied the ionoacoustic signal of the Bragg peak in experiments using a 20 MeV proton beam with its correspondingly localized energy deposition, demonstrating submillimeter position resolution and providing a deep insight in the correlation between the acoustic signal and Bragg peak shape. These results, together with earlier experiments and new simulations (including the results in this study) at higher energies, suggest ionoacoustics as a technique for range verification in particle therapy at locations, where the tumor can be localized by ultrasound imaging. This acoustic range verification approach could offer the possibility of combining anatomical ultrasound and Bragg peak imaging, but further studies are required for translation of these findings to clinical application.

Ionoacoustic characterization of the proton Bragg peak with submillimeter accuracy.

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Ionoacoustic characterization of the proton Bragg peak with submillimeter accuracy.