The sharp spatial and temporal dose gradients of pulsed ion beams result in an acoustic emission (ionoacoustics), which can be used to reconstruct the dose distribution from measurements at different positions. The accuracy of range verification from ionoacoustic images measured with an ultrasound linear array configuration is investigated both theoretically and experimentally for monoenergetic proton beams at energies relevant for pre-clinical studies (20 and 22 MeV). The influence of the linear sensor array arrangement (length up to 4 cm and number of elements from 5 to 200) and medium properties on the range estimation accuracy are assessed using time-reversal reconstruction. We show that for an ideal homogeneous case, the ionoacoustic images enable a range verification with a relative error lower than 0.1%, however, with limited lateral dose accuracy. Similar results were obtained experimentally by irradiating a water phantom and taking into account the spatial impulse response (geometry) of the acoustic detector during the reconstruction of pressures obtained by moving laterally a single-element transducer to mimic a linear array configuration. Finally, co-registered ionoacoustic and ultrasound images were investigated using silicone inserts immersed in the water phantom across the proton beam axis. By accounting for the sensor response and speed of sound variations (deduced from co-registration with ultrasound images) the accuracy is improved to a few tens of micrometers (relative error less than to 0.5%), confirming the promise of ongoing developments for ionoacoustic range verification in pre-clinical and clinical proton therapy applications.

The characteristic depth dose deposition of ion beams, with a maximum at the end of their range (Bragg peak) allows for local treatment delivery, resulting in better sparing of the adjacent healthy tissues compared to other forms of external beam radiotherapy treatments. However, the optimal clinical exploitation of the favorable ion beam ballistic is hampered by uncertainties in the in vivo Bragg peak position. Ionoacoustics is based on the detection of thermoacoustic pressure waves induced by a properly pulsed ion beam (e.g., produced by modern compact accelerators) to image the irradiated volume. Co-registration between ionoacoustics and ultrasound imaging offers a promising opportunity to monitor the ion beam and patient anatomy during the treatment. Nevertheless, the detection of the ionoacoustic waves is challenging due to very low pressure amplitudes and frequencies (mPa/kHz) observed in clinical applications. We investigate contrast agents to enhance the acoustic emission. Ultrasound microbubbles are used to increase the ionoacoustic frequency around the microbubble resonance frequency. Moreover, India ink is investigated as a possible mean to enhance the signal amplitude by taking advantage of additional optical photon absorption along the ion beam and subsequent photoacoustic effect. We report amplitude increase of up to 200% of the ionoacoustic signal emission in the MHz frequency range by combining microbubbles and India ink contrast agents.

Objectives Image guidance and precise irradiation are fundamental to ensure the reliability of small animal oncology studies. Accurate positioning of the animal and the in-beam monitoring of the delivered radio-therapeutic treatment necessitate several imaging modalities. In the particular context of proton therapy with a pulsed beam, information on the delivered dose can be retrieved by monitoring the thermoacoustic waves resulting from the brief and local energy deposition induced by a proton beam (ionoacoustics). The objective of this work was to fabricate a multimodal phantom (x-ray, proton, ultrasound, and ionoacoustic) allowing for sufficient imaging contrast for all the modalities. Approach The phantom anatomical parts were extracted from mouse computed tomography scans and printed using polylactic acid (organs) and a granite / polylactic acid composite (skeleton). The anatomical pieces were encapsulated in silicone rubber to ensure long term stability. The phantom was imaged using x-ray cone-beam computed tomography, proton radiography, ultrasound imaging, and monitoring of a 20 MeV pulsed proton beam using ionoacoustics. Main results The anatomical parts could be visualized in all the imaging modalities validating the phantom capability to be used for multimodal imaging. Ultrasound images were simulated from the x-ray cone-beam computed tomography and co-registered with ultrasound images obtained before the phantom irradiation and low-resolution ultrasound images of the mouse phantom in the irradiation position, co-registered with ionoacoustic measurements. The latter confirmed the irradiation of a tumor surrogate for which the reconstructed range was found to be in reasonable agreement with the expectation. Significance This study reports on a realistic small animal phantom which can be used to investigate ionoacoustic range (or dose) verification together with ultrasound, x-ray, and proton imaging. The co-registration between ionoacoustic reconstructions of the impinging proton beam and x-ray imaging is assessed for the first time in a pre-clinical scenario.

Objectives – The energy deposited in a medium by a pulsed proton beam results in the emission of thermoacoustic waves, also called ionoacoustics (IA). The proton beam stopping position (Bragg peak) can be retrieved from a time-of-flight analysis (ToF)
of IA signals acquired at different sensor locations (multilateration). This work aimed to assess the robustness of multilateration methods in proton beams at pre-clinical energies for the development of a small animal irradiator.
Approach – The accuracy of multilateration performed using different algorithms; namely, time of arrival (TOA) and time difference of arrival (TDOA), was investigated in-silico for ideal point sources in the presence of realistic uncertainties on the ToF
estimation and ionoacoustic signals generated by a 20 MeV pulsed proton beam stopped in a homogeneous water phantom. The localisation accuracy was further investigated experimentally based on two different measurements with pulsed monoenergetic proton
beams at energies of 20 and 22 MeV.
Main results – It was found that the localisation accuracy mainly depends on the position of the acoustic detectors relative to the proton beam due to spatial variation of the error on the ToF estimation. By optimally positioning the sensors to reduce
the ToF error, the Bragg peak could be located in-silico with an accuracy better than 90μm (2 % error). Localisation errors going up to 1 mm were observed experimentally due to inaccurate knowledge of the sensor positions and noisy ionoacoustic signals.
Significance – This study gives a first overview of the implementation of different multilateration methods for ionoacoustics-based Bragg peak localisation in two- and three-dimensions at pre-clinical energies. Different sources of uncertainty were investigated, and their impact on the localisation accuracy was quantified in-silico and experimentally.

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