The ionoacoustic signal – generated when an ion beam passes through tissue and induces localized thermal expansion – is directly correlated to the Bragg peak position and promises a cost-effective means to characterize dose distribution. A team headed up at LMU Munich has now demonstrated ionoacoustic measurements of proton range using a clinical treatment system, at clinically relevant proton energies and under optimized conditions (Phys. Med. Biol. 62 L20).

"Previous attempts at ionoacoustic measurements on a clinical system were made in Japan using a synchrotron but in less suitable irradiation conditions, which made precise range measurements infeasible," said corresponding author Walter Assmann. "A more recent attempt was made in the USA using a conventional IBA isochronous cyclotron with artificial source pulsing. But due to a rather long pulse width, only an accuracy of some millimetres could be achieved."

The LMU team, in collaboration with IBA and the Centre Antoine-Lacassagne, used the new compact ProteusONE superconducting synchrocyclotron installed in the centre in Nice, France. The synchrocyclotron delivers intense, microsecond-short proton pulses at 1 kHz repetition rate, ideally suited for ionoacoustic measurements, which are influenced by the spatial dose distribution and temporal pulse length.

"The ion pulse width should be shorter than the acoustic travel time across the Bragg peak region, which is about 5 µs for the lowest clinically used proton energy," explained first author Sebastian Lehrack. "Only in this case will the ionoacoustic signal convey time information suitable for submillimetre range determination."

Phantom studies

Lehrack, Assmann and colleagues performed ionoacoustic range measurements in a water phantom using proton beams with energies from 145 to 227 MeV and the ultrasound detector positioned distal to the Bragg peak on the proton beam axis. To maximize precision, they employed two trigger signals: one from the rotating capacitor (rotco) that defines the synchrocyclotron's RF frequency, which was used to start the data acquisition; and the other deduced from proton-induced prompt gamma rays.

"The first trigger was found to have a jitter close to 1 µs, which would destroy our submillimetre precision," explained senior author Katia Parodi. "The time-of-flight measurement used to get the Bragg peak position needs a more stable trigger, which was derived from a fast scintillator detecting prompt gamma radiation."

The Bragg peak position was calculated from the time difference between the prompt gamma trigger and the acoustic compression pulse. The absolute proton range in water can then be obtained by subtracting this Bragg peak position from the measured distance between the detector and the water surface.

The researchers compared their ionoacoustic range measurements to range data recorded previously using a Stingray plane-parallel ionization chamber. Range values agreed well, with a maximum difference of 646 µm. For a 200 MeV proton beam, they repeated the Stingray measurement during the ionoacoustic experiment, and observed a difference of just 27 µm between range values. Examining variations around the mean of five ionoacoustic measurements (at each of 200, 219 and 220 MeV) revealed a measurement reproducibility uncertainty of less than 400 µm.

The team also performed relative range shift measurements by directly analysing the ionoacoustic waveforms, acquired using the rotco trigger only. They determined range shifts from 227 MeV to 226 and 145 MeV, and compared the results to corresponding Stingray values. The mean ionoacoustic values of the two shifts agreed with the Stingray values to within 1 mm.

"Without a precise start trigger signal, absolute range determination is not possible. But a (relative) range shift measurement for different proton energies was still possible with submillimetre accuracy, though large uncertainty due to the trigger jitter," noted Assmann. "Therefore, if a range shift is of interest only, the RF-trigger can be used without any further detector or trigger."

Look to the future

The authors note that the main challenge for clinical application of ionoacoustics is improving the signal-to-noise ratio while reducing dose. "To this end, we are looking into several directions, such as development of more sensitive detectors, characterization of ionoacoustics in heterogeneous media and signal processing in the frequency domain," said Lehrack.

"Another goal is related to co-registration of the ionoacoustic signal with ultrasound imaging of the tumour volume, which is in our view, one of the main advantages of the ionoacoustic method," Parodi told medicalphysicsweb. "Due to the common underlying acoustic waves, such a combination in dedicated detector arrays can circumvent serious issues due to tissue heterogeneities. Thus, the ionoacoustic approach could offer real-time motion compensation for image-guided ion therapy, based on both anatomy and range determination."

Related articles in PMB
Submillimeter ionoacoustic range determination for protons in water at a clinical synchrocyclotron
Sebastian Lehrack et al Phys. Med. Biol. 62 L20
Thermoacoustic range verification using a clinical ultrasound array provides perfectly co-registered overlay of the Bragg peak onto an ultrasound image
S K Patch et al Phys. Med. Biol. 61 5621
How proton pulse characteristics influence protoacoustic determination of proton-beam range: simulation studies
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