3D optically-stimulated-luminescence-based dosimetry using LYSO:Ce scintillators

The search for a reusable 3D dosimeter is ongoing and motivated by the impact it would have on development and verification of complex modalities in radiotherapy. We present a proof-of-concept 3D measurement of a proton-irradiated LYSO:Ce scintillator, using the resettable photon-emission mechanism known as optically stimulated luminescence and a novel optical readout system. Through this demonstration, we show that LYSO:Ce, in addition to being capable of real-time beam imaging, can be employed as a reusable post-irradiation 3D dosimeter with high spatial resolution.


Introduction
The complexity of radiation therapy is steadily increasing, with new strategies for tumour imaging and target definitions, treatment planning, and dose delivery being active topics of research and product development [1,2].Therefore, the need to validate treatment plans for specific treatment modalities in three dimensions (3D) is likewise increasing.Such quality assurance can be provided by 3D dosimeters, which in most cases consist of gel-based materials with an irreversible chemical response to ionizing radiation that can be mapped using optical computed tomography [3][4][5][6].A specific example is siliconebased radiochromic dosimeters, which have recently been used to investigate the effects of deformation during irradiation [7] and to demonstrate dose-response in the presence of the magnetic field in novel MR-guided radiotherapy [8].Although much effort has been invested in solving challenges like quenching and dose-rate dependence [9], these dosimeters are by design one-time use dosimeters that require batch-specific calibration curves [10], limiting their feasibility in a clinical setting.
The search for a reusable 3D dosimeter is ongoing, and as previously suggested [11][12][13][14], optically stimulated luminescence (OSL) based dosimetry is a prime candidate.OSL is a photon-emission mechanism available in certain large-band-gap materials, which are able to trap and store information about energy deposition from ionizing radiation.Upon irradiation, free electrons and holes generated by the ionizing radiation immediately thermalize to the lowest available energy in their respective bands.From here, the electrons and holes may be captured to metastable trap states, energetically residing within the band gap of the material, effectively storing information about the deposited dose.This information can then later be retrieved by optically exciting the trapped electrons back to the conduction band, from where they may recombine radiatively through a recombination center.Embedding OSL-active nanoparticles in a transparent polymer matrix can potentially provide a reusable tissue-equivalent dosimeter.A strong candidate for such OSL-active nanoparticles is copper-doped LiF [15], and recent studies have demonstrated the potential of commercial LiF:Mg,Cu,P (MCP) powder for OSL-based 2D film dosimetry [16][17][18].
Scintillators represent the forefront of room-temperature radiation detection and spectroscopy, and have also found applications for real-time beam imaging in the form of liquid scintillators [19,20].Moreover, OSL properties have been reported in cerium-doped compounds of the lutetium orthosilicate scintillator family Lu(2-x)YxSiO5 (LYSO:Ce) [21][22][23], indicating that these scintillators could also be interesting for dosimetry.A recent study [24] found the OSL yield of commercial LYSO:Ce crystals to be high enough to enable high-spatial-resolution dose imaging in 3D for photon and electron excitation.The aim of the presented study was to perform proof-of-concept 3D measurements of a proton-irradiated LYSO:Ce crystal using a novel optical readout system, to demonstrate the potential of OSL-based 3D dosimetry.

Methods and Materials
An optical readout system for OSL-based 3D dosimetry has been developed.In short, this system reads out the OSL-signal from inside the bulk of OSL-based dosimeters in a layer-wise manner, using a CCD camera and a moving light sheet.The light sheet and dosimeter are positioned on translation stages and move in a relative way, enabling the sheet to stimulate the dosimeter in a selected layer, emptying the traps and emitting OSL-photons.These photons are then imaged in 2D onto the SOPHIA-2048BR CCD camera from Princeton Instruments using an APO Macro objective from JenOptik and appropriate optical filters.Moving the light sheet provides the third dimension, and the 2D measurements can be stacked post measurement to yield a 3D distribution.The measurements presented in this contribution were acquired using a light-sheet width of 1 mm and a 4x4 binning of the CCD, yielding a voxel size of 0.18x0.18x1.00mm 3 .Readouts were performed using an integration time of 2 s at each layer, scanning layers by moving the sheet towards the camera, and repeating this 40 times.As described in detail in a previous paper from our group [24], this readout method enables detection of estimated doses in LYSO:Ce crystals as low as 0.05 Gy with 2 % precision in voxel volumes of 1 mm 3 .
The measurements presented in this contribution were executed using a 20x20x20 mm 3 LYSO:Ce crystal from Crystal Photonics Inc.The crystal was irradiated with 4233 monitor units of 100 MeV protons (equivalent to ~10 10 100 MeV protons according to simulations) at the Danish Center for Particle Therapy, Aarhus University Hospital, and read out using the described system an hour after irradiation.An inexpensive CMOS-camera was placed next to the crystal during this irradiation to qualitatively image the scintillation response.A 2 cm SolidWater ® slab was placed in front of the crystal during irradiation to allow for higher beam energy with a close-to-minimum spatial divergence at the isocenter, and still ensure full enclosure of the Bragg peak inside the bulk of the crystal.The energy deposition of this irradiation was estimated using Monte Carlo-based Geant4 simulations [25,26] (FTPT_BERT physics list), tracking the step-wise energy deposition of individual protons from a collimated beam and scoring the post-step coordinates for each energy deposition.The results of this simulation were postprocessed to yield a 3D dose-to-medium map, using custom-made software written in Python.

Results and Discussion
Figure 1a displays a true-color image of the scintillation from the proton-irradiated LYSO:Ce crystal during irradiation and clearly shows the Bragg peak of the proton beam within the crystal.This image confirms the abilities of these crystals as real-time beam imaging tools, using e.g.multiple high-quality cameras to image the scintillation response from different angles in a tomographic approach as was demonstrated in [19,20] After the irradiation, the OSL emission was measured using the optical readout system, yielding the 3D distribution displayed in Fig. 1b.Here, the colormap has been adjusted to have an increasing transparency in regions of very low counts to make the Bragg peak more visible.Note that the light sheet scans in the z-direction and spans the xy-plane, entering the crystal from x = 20 mm.The sheet has been truncated to only stimulate the center-most 18 mm in the y-direction, to minimize scattering from the edges of the crystal which may cause premature readout of adjacent layers.A similar choice was made for the scanned z-range, where only sheet positions from 17.5 to 2.5 mm were read out, likewise to minimize scattering from the edges.
Projections onto each spatial axis of the signal can be seen in Fig. 1c-e along with projections of the simulated dose distribution.A good qualitative agreement is seen between data and simulation, with an especially good agreement in the falling edge of the Bragg peak in Fig. 1c, where the data and simulation have identical shapes.Moreover, the peak-to-entrance-ratios of the measurement and the simulation were estimated to be 4.2 and 3.7, respectively, varying by only 15 %.We attribute the submm deviation in location (x-direction) of the Bragg peak to potential misalignments of the crystal during irradiation and/or readout and the simplified proton beam profile and material specifications used for the simulation.These measurements demonstrate the ability to read out information on the time- integrated dose distribution from OSL-based dosimeters exposed to proton-irradiation with sub-mm 3 spatial resolution in 3D.Moreover, the number of detected OSL photons per dose per voxel volume is in agreement with the value reported in [24], indicating the OSL light yield of LYSO:Ce to be within the same order of magnitude for proton and electron excitation.
The high density of LYSO:Ce (7.1 g/cm 3 ) inevitably makes these crystals less suitable for quality assurance in clinical radiotherapy.However, the presented results demonstrate the potential for 3D postirradiation dose-imaging and serve as a proof-of-concept for the readout method and OSL-based 3D dosimetry.

Conclusion
We have demonstrated the application of LYSO:Ce scintillators as OSL-based reusable post-irradiation dosimeters for proton irradiation with high 3D spatial resolution.In accessing the information on the dose-distribution stored in these crystals, we have presented a proof-of-concept readout method for OSL-based dosimeters, and thus demonstrated the potential of OSL-based 3D dosimetry.

Figure 1 .
Figure 1.Readouts from a proton irradiated LYSO:Ce crystal.a) Image of the scintillation from the LYSO:Ce crystal during irradiation.Note that the camera angle gives rise to an optical artefact, exaggerating the slight displacement of the beam from the center of the crystal.b) 3D illustration of background-subtracted post-irradiation OSL readout of the crystal.The color-map has been adjusted to let voxels of very low intensity have increasingly high transparency to accentuate the Bragg Peak.Note that only the centremost 16 and 18 mm in the z-direction and y-direction, respectively, were stimulated.The full extent of the crystal (20x20x20 mm 3 ) is indicated with the black lines.The voxel size is 0.18x0.18x1.0mm 3 .c-e) Projections of the OSL readout displayed in b) onto each spatial axis along with a simulation indicating the estimated doses in the projected voxels with sizes indicated on the respective figures.