Dictionary-based software for proton dose reconstruction and submilimetric range verification.

Objective.This paper presents a new method for fast reconstruction (compatible with in-beam use) of deposited dose during proton therapy using data acquired from a PET scanner. The most innovative feature of this novel method is the production of noiseless reconstructed dose distributions from which proton range can be derived with high precision.Approach.A new MLEM & simulated annealing (MSA) algorithm, developed especially in this work, reconstructs the deposited dose distribution from a realistic pre-calculated activity-dose dictionary. This dictionary contains the contribution of each beam in the plan to the 3D activity and dose maps, as calculated by a Monte Carlo simulation. The MSA algorithm, usinga prioriinformation of the treatment plan, seeks for the linear combination of activities of the precomputed beams that best fits the observed PET data, obtaining at the same time the deposited dose.Main results.the method has been tested using simulated data to determine its performance under 4 different test cases: (1) dependency of range detection accuracy with delivered dose, (2) in-beam versus offline verification, (3) ability to detect anatomical changes and (4) reconstruction of a realistic spread-out Bragg peak. The results show the ability of the method to accurately reconstruct doses from PET data corresponding to 1 Gy irradiations, both in intra-fraction and inter-fraction verification scenarios. For this dose level (1 Gy) the method was able to spot range variations as small as 0.6 mm.Significance.out method is able to reconstruct dose maps with remarkable accuracy from clinically relevant dose levels down to 1 Gy. Furthermore, due to the noiseless nature of reconstructed dose maps, an accuracy better than one millimeter was obtained in proton range estimates. These features make of this method a realistic option for range verification in proton therapy.

Evaluation of natural background levels of high mountain karst aquifers in complex hydrogeological settings. A Gaussian mixture model approach in the Port del Comte (SE, Pyrenees) case study.

The hydrogeological processes driving the hydrochemical composition of groundwater in the alpine pristine aquifer system of the Port del Comte Massif (PCM) are characterized through the multivariate statistical techniques Principal Component Analysis (PCA) and Gaussian Mixture Models (GMM) in the framework of Compositional Data (CoDa) analysis. Also, the groundwater Natural Background Levels (NBLs) for NO3 and SO4 and Cl are evaluated, which are specially important for indicating the occurrence of groundwater contamination derived from the anthropic activities conducted in the PCM. The different hydrogeochemical facies found in the aquifer system of the PCM comprises low mineralized Ca-HCO3 water for the main Eocene karst aquifer, and Ca-SO4 and highly mineralized NaCl water types in the minor aquifers discharging from the PCM. The NBL values of SO4, Cl and NO3 obtained for the main karst aquifer are 14.33, 4.06 and 6.55 mg/L, respectively. These values are 35, 3 and 1.2 times lower than the respective official NBLs values that were determined by the water administration to be compared with in the case of conducting a pollution assessment characterization in the main karst aquifer. Official overestimation of NBLs can put important groundwater resources in the PCM at risk.

Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons.

In order to integrate radiobiological modelling with clinical treatment planning for proton radiotherapy, we extended our in-house treatment planning system FoCa with a 3D analytical algorithm to calculate linear energy transfer (LET) in voxelized patient geometries. Both active scanning and passive scattering delivery modalities are supported. The analytical calculation is much faster than the Monte-Carlo (MC) method and it can be implemented in the inverse treatment planning optimization suite, allowing us to create LET-based objectives in inverse planning. The LET was calculated by combining a 1D analytical approach including a novel correction for secondary protons with pencil-beam type LET-kernels. Then, these LET kernels were inserted into the proton-convolution-superposition algorithm in FoCa. The analytical LET distributions were benchmarked against MC simulations carried out in Geant4. A cohort of simple phantom and patient plans representing a wide variety of sites (prostate, lung, brain, head and neck) was selected. The calculation algorithm was able to reproduce the MC LET to within 6% (1 standard deviation) for low-LET areas (under 1.7 keV µm(-1)) and within 22% for the high-LET areas above that threshold. The dose and LET distributions can be further extended, using radiobiological models, to include radiobiological effectiveness (RBE) calculations in the treatment planning system. This implementation also allows for radiobiological optimization of treatments by including RBE-weighted dose constraints in the inverse treatment planning process.

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes.

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning. The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems. The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa's most accurate algorithm) for all cases considered. Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

Fast range switching of passively scattered proton beams using a modulation wheel and dynamic beam current modulation.

In proton radiotherapy, the range of particles in the patient body is determined by the energy of the protons. For most systems, the energy selection time is on the order of a few seconds, which becomes a serious obstacle for continuous dose delivery techniques requiring adaptive range modulation. This work analyses the feasibility of using the range modulation wheel, an element in the beamline used to form the spread-out Bragg peak (SOBP), to produce near-instantaneous changes not only in the modulation, but also in the range of the beam. While delivering proton beams in double scattering mode, the beam current can be synchronized with the range modulation wheel rotation by defining a current modulation pattern. Different current modulation patterns were computed from Monte Carlo simulations of our double scattering nozzle to range shift an SOBP of initial range 15 cm by varying degrees of up to ∼9 cm. These patterns were passed to the treatment control system at our institution and the resulting measured depth-dose distributions were analysed in terms of flatness, distal penumbra and relative irradiation time per unit mid-SOBP dose. Suitable SOBPs were obtained in all cases, with the maximum range shift being limited only by the maximum thickness of the wheel. The distal dose fall-off (80% to 20%) of the shifted peaks was broadened to about 1 cm, from the original 0.5 cm, and the predicted overhead in delivery time showed a linear increase with the amount of the shift. By modulating the beam current in clinical scattered proton beams equipped with a modulation wheel, it is possible to dynamically modify the in-patient range of the SOBP without adding any specific hardware or compensators to the beamline. A compromise between sharper distal dose fall-off and lower delivery time can be achieved and is subject to optimization.

Influence of the delta ray production threshold on water-to-air stopping power ratio calculations for carbon ion beam radiotherapy.

Previous calculations of the water-to-air stopping power ratio (s(w,)(air)) for carbon ion beams did not involve tracking of delta ray electrons, even though previous calculations with protons predict an effect up to 1%. We investigate the effect of the delta ray production threshold in s(w,)(air) calculations and propose an empirical expression which takes into account the effect of the delta ray threshold as well as the uncertainty in the mean ionization potentials (I-values) of air and water. The formula is derived from the results of Monte Carlo calculations using the most up-to-date experimental data for I-values and a delta ray production threshold of 10 keV. It allows us to reduce the standard uncertainty in s(w,)(air) below 0.8%, instead of the current 2% given in international protocols, which results in a reduction of the overall uncertainty for absolute dosimetry based on air-filled ionization chambers.

Experimental study of the water-to-air stopping power ratio of monoenergetic carbon ion beams for particle therapy.

Reference dosimetry with ionization chambers requires a number of chamber-specific and beam-specific calibration factors. For carbon ion beams, IAEA report TRS-398 yields a total uncertainty of 3% in the determination of the absorbed dose to water, for which the biggest contribution arises from the water-to-air stopping power ratio (s(w, air)), with an uncertainty of 2%. The variation of (s(w, air)) along the treatment field has been studied in several Monte Carlo works presented over the last few years. Their results were, in all cases, strongly dependent on the choice of mean ionization potentials (I-values) for air and water. A smaller dependence of (s(w, air)) with penetration depth was observed. Since a consensus on I(w, air) and I(air) has not yet been reached, the validity of such studies for clinical use cannot be assessed independently. Our approach is based on a direct experimental measurement of water-equivalent thicknesses of different air gaps at different beam energies. A theoretical expression describing the variation of the stopping power ratio with kinetic energy, s(w,air)(E), was derived from the Bethe-Bloch formula and fit to the measured data, yielding a coherent pair of I(w) and I(air) values with I(air)/I(w) = 1.157 ± 0.023. Additionally, the data from five different beam energies were combined in an average value of s(w,air) = 1.132 ± 0.003 (statistical) ± 0.003 (variation over energy range), valid for monoenergetic carbon ion beams at the plateau area of the depth dose distribution. A detailed uncertainty analysis was performed on the data, in order to assess the limitations of the method, yielding an overall standard uncertainty below 1% in s(w,air)(E). Therefore, when properly combined with the appropriate models for the fragment spectra, our experimental work can contribute to narrow the uncertainty margins currently in use in absorbed dose to water determination for dosimetry of carbon ion beam radiotherapy.