Options for range control include PET and prompt gamma imaging (PGI), both of which detect secondary particles created when the incident beam interacts with nuclei within the body. While PET has already proved useful for post-treatment verification, PGI offers the opportunity to monitor the range of proton pencil beams in real time. With this aim, a European research team is developing a new type of prompt gamma camera that uses a slit collimator to obtain a one-dimensional projection of the beam path on a scintillation detector (Phys. Med. Biol. 57 3371).

"Prompt photons are emitted within less than one nanosecond. This is both a great advantage and a difficulty with respect to the established PET technique," explained Julien Smeets, from Université Libre de Bruxelles in Belgium. "With prompt gammas, we don't have to wait for positron emitters to decay, and the measured signal is not corrupted by washout effects or activity remaining from previous fields. The difficulty is related to the necessary high-count-rate capability of the detector."

Optimal design

To investigate PGI in more depth, Smeets and colleagues – also from Politecnico di Milano in Italy, its spin-off XGLab and IBA of Belgium – performed Monte Carlo simulations of a prompt gamma camera using a cylindrical PMMA target irradiated with a pencil beam of 160 MeV protons. For simulations, a segmented scintillation detector was placed 30 cm from the beam axis and the slit collimator located halfway between. Examining the particles leaving the target revealed that the photon profile sharply decreased at the Bragg peak depth, with 4–5 MeV photons providing the clearest indication of beam range. The neutron component was not correlated with range.

The researchers also used Monte Carlo simulations to trade off the camera's spatial resolution and detection efficiency. The following parameters were selected as optimal: a tungsten alloy collimator with a thickness of 40 mm, a slit angle of 63.4° and a slit width of 6 mm; a 10 mm thick LYSO scintillator with a 5 mm segment width, and an energy selection window of 3–6 MeV.

"The strength of the slit geometry is that it focuses on a single objective: measuring the depth at which the beam stops in the patient," said Smeets. "Three contradictory qualities are desired for a prompt gamma camera: high counting statistics, high correlated-to-uncorrelated-events ratio and high spatial resolution. The slit design favours the counting statistics, which to us seems to be the most critical parameter. High counting statistics make it realistic to retrieve the range with millimetre accuracy for numbers of protons compatible with single pencil beams."

The accuracy of the simulations was assessed by comparison with spectrometry measurements of secondary particles emitted by a PMMA target during 160 MeV proton irradiation. Excellent agreement with simulations was observed when using subtraction methods to isolate prompt gammas in direct incidence.

To evaluate the slit camera performance, the researchers simulated proton beam range shifts at 100, 160 and 230 MeV, for various numbers of incident protons. The camera was initially placed with its slit aligned with the expected beam range, and then the target was shifted along the beam axis and the corresponding shift of the simulated detection profile estimated. Accurate shifts were retrieved even from profiles with poor statistics. A standard deviation of 1 mm was seen down to 5 x 108 incident protons for all energies.

Prototype tests

The team then built a prototype slit camera, based on the HiCam, a compact Anger gamma camera that uses arrays of silicon drift detectors. The HiCam was modified to image prompt gammas using the abovementioned optimized collimator and scintillator parameters.

To assess the camera's ability to detect range shifts, they used an experimental set-up that replicated simulations, with 100 and 160 MeV proton pencil beams incident along the axis of a cylindrical PMMA target, the HiCam with the LYSO scintillator placed at 30 cm and the tungsten collimator located halfway between. As in the simulation study, the camera was initially centred at the expected range depth and then the target was shifted along the beam axis.

Selecting events in the 3–6 MeV energy window resulted in detection profiles that exhibited the same fall-off at the Bragg peak depth as in the simulations, but offset by a higher background of uncorrelated particles. The observed detection profiles reproduced the target shifts, confirming the camera's ability to identify 1 mm range shifts.

To estimate range shift from a measured detection profile, it was compared to a reference profile generated by Monte Carlo simulation. Accurate shifts could be calculated even from measured profiles that appeared noisy.

The researchers concluded that the performance of this prototype camera holds promise for real-time proton beam range measurements at 100 and 160 MeV, with millimetre accuracy. Smeets noted that measurements have now been successfully repeated using 230 MeV proton beams, validating the concept for the entire range of clinical proton beam energies.

"A second prototype is now being designed," Smeets told medicalphysicsweb. "This will answer two questions: Can we handle the high count rate in clinical routine? And what is the effect of inhomogeneities on the accuracy of the range measurement?"

These research activities are conducted in the framework of the EU FP7 projects ENVISION and ENTERVISION and are supported by the Belgian FNRS and IBA.

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