Enhancing adaptive proton therapy through CBCT images: Synthetic head and neck CT generation based on 3D vision transformers.

BACKGROUND: Proton therapy is a form of radiotherapy commonly used to treat various cancers. Due to its high conformality, minor variations in patient anatomy can lead to significant alterations in dose distribution, making adaptation crucial. While cone-beam computed tomography (CBCT) is a well-established technique for adaptive radiation therapy (ART), it cannot be directly used for adaptive proton therapy (APT) treatments because the stopping power ratio (SPR) cannot be estimated from CBCT images. PURPOSE: To address this limitation, Deep Learning methods have been suggested for converting pseudo-CT (pCT) images from CBCT images. In spite of convolutional neural networks (CNNs) have shown consistent improvement in pCT literature, there is still a need for further enhancements to make them suitable for clinical applications. METHODS: The authors introduce the 3D vision transformer (ViT) block, studying its performance at various stages of the proposed architectures. Additionally, they conduct a retrospective analysis of a dataset that includes 259 image pairs from 59 patients who underwent treatment for head and neck cancer. The dataset is partitioned into 80% for training, 10% for validation, and 10% for testing purposes. RESULTS: The SPR maps obtained from the pCT using the proposed method present an absolute relative error of less than 5% from those computed from the planning CT, thus improving the results of CBCT. CONCLUSIONS: We introduce an enhanced ViT3D architecture for pCT image generation from CBCT images, reducing SPR error within clinical margins for APT workflows. The new method minimizes bias compared to CT-based SPR estimation and dose calculation, signaling a promising direction for future research in this field. However, further research is needed to assess the robustness and generalizability across different medical imaging applications.

Material decomposition maps based calibration of dual energy CT scanners for proton therapy planning: a phantom study.

We introduce a new calibration method for dual energy CT (DECT) based on material decomposition (MD) maps, specifically iodine and water MD maps. The aim of this method is to provide the first DECT calibration based on MD maps. The experiments were carried out using a general electric (GE) revolution CT scanner with ultra-fast kV switching and used a density phantom by GAMMEX for calibration and evaluation. The calibration process involves several steps. First, we tested the ability of MD values to reproduce Hounsfield unit (HU) values of single energy CT (SECT) acquisitions and it was found that the errors were below 1%, validating their use for HU reproduction. Next, the different definitions of computedZvalues were compared and the robustness of the approach based on the materials' composition was confirmed. Finally, the calibration method was compared with a previous method by Bourqueet al, providing a similar level of accuracy and superior performance in terms of precision. Overall, this novel DECT calibration method offers improved accuracy and reliability in determining tissue-specific physical properties. The resulting maps can be valuable for proton therapy treatments, where precise dose calculations and accurate tissue differentiation are crucial for optimal treatment planning and delivery.

Radical Production with Pulsed Beams: Understanding the Transition to FLASH.

Ultra-high dose rate (UHDR) irradiation regimes have the potential to spare normal tissue while keeping equivalent tumoricidal capacity than conventional dose rate radiotherapy (CONV-RT). This has been called the FLASH effect. In this work, we present a new simulation framework aiming to study the production of radical species in water and biological media under different irradiation patterns. The chemical stage (heterogeneous phase) is based on a nonlinear reaction-diffusion model, implemented in GPU. After the first 1 µs, no further radical diffusion is assumed, and radical evolution may be simulated over long periods of hundreds of seconds. Our approach was first validated against previous results in the literature and then employed to assess the influence of different temporal microstructures of dose deposition in the expected biological damage. The variation of the Normal Tissue Complication Probability (NTCP), assuming the model of Labarbe et al., where the integral of the peroxyl radical concentration over time (AUC-ROO) is taken as surrogate for biological damage, is presented for different intra-pulse dose rate and pulse frequency configurations, relevant in the clinical scenario. These simulations yield that overall, mean dose rate and the dose per pulse are the best predictors of biological effects at UHDR.

Performance of a new star-bar phantom designed for MTF calculations in x-ray imaging systems.

PURPOSE: A new phantom, designed and manufactured for modulation transfer function (MTF) calculations is presented in this work. The phantom has a star-bar pattern and is manufactured in stainless steel. Modulation transfer function determinations are carried out with the new phantom and with an edge phantom to compare their performance and to compare them with previous theoretical predictions. METHODS: The phantoms are imaged in an x-ray imaging system using different beam qualities and different entrance air KERMA. Methods, previously developed for synthetic images and simulations, are adapted to real measurements, solving practical implementation issues. RESULTS: In the case of the star-bar, in order to obtain optimal MTF determinations it is necessary to accurately determine the center of the pattern. Also, to avoid underestimates in MTF calculations, the length in pixels of each of the scanning circumferences must be an integer multiple of the number of cycles in the pattern. Both methods, star-bar and edge, give similar mean values of the MTF in all cases analyzed. Also, the dependence with frequency of the experimental MTF standard deviation (SD) agrees with the theoretical expressions presented in previous works. In this regard, the precision is better for the star-bar method than for the edge and differences in precision between both methods are higher for the lowest beam quality. CONCLUSIONS: The star-bar phantom can be used for MTF determinations with the advantage of having an improved precision. However, precision is reduced when the radiation quality increases. This fact suggests that, for the highest beam qualities, materials with an attenuation coefficient greater than that of steel should be used to manufacture the phantom.

Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms.

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate "FLASH" irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

A new method for modelling the tongue-and-groove in treatment planning systems.

Commercial TPSs typically model the tongue-and-groove (TG) by extending the projections of the leaf sides by a certain constant width. However, this model may produce discrepancies of as much as 7%-10% in the calculated average doses, especially for the High Definition multi-leaf collimator (MLC) (Hernandez et al 2017 Phys. Med. Biol. 62 6688-707). The purpose of the present study is to introduce and validate a new method for modelling the TG that uses a non constant TG width. We provide the theoretical background and a detailed methodology to determine the optimal shape of this TG width from measurements and we fit an empirical function to the TG width that depended on two parameters [Formula: see text] and [Formula: see text]. Parameter [Formula: see text] represents the TG width and [Formula: see text] introduces a curvature correction in the width near the leaf tip end. The new TG model was implemented in MATLAB and when the curvature correction was zero ([Formula: see text]) it caused the same discrepancies as the constant width model used by the Eclipse TPS. On the other hand, when the experimentally determined [Formula: see text] was used the new model's calculations were in close agreement with measurements, with all differences in average doses [Formula: see text]1%. Additionally, film dosimetry was used to successfully validate the potential of the new TG model to recreate the fine spatial details associated to TG effects. We also showed that the parameters [Formula: see text], [Formula: see text] depend solely on the MLC design by evaluating three different linear accelerators for each MLC model considered, namely Varian's High Definition and Millennium120 MLCs. In conclusion, a new method was presented that greatly improves the TG modelling. The present method can be easily implemented in commercial TPSs and has the potential to further increase their accuracy, especially for MLCs with rounded leaf ends.

Monte Carlo uncertainty analysis of dose estimates in radiochromic film dosimetry with single-channel and multichannel algorithms.

PURPOSE: To provide a multi-stage model to calculate uncertainty in radiochromic film dosimetry with Monte-Carlo techniques. This new approach is applied to single-channel and multichannel algorithms. MATERIAL AND METHODS: Two lots of Gafchromic EBT3 are exposed in two different Varian linacs. They are read with an EPSON V800 flatbed scanner. The Monte-Carlo techniques in uncertainty analysis provide a numerical representation of the probability density functions of the output magnitudes. From this numerical representation, traditional parameters of uncertainty analysis as the standard deviations and bias are calculated. Moreover, these numerical representations are used to investigate the shape of the probability density functions of the output magnitudes. Also, another calibration film is read in four EPSON scanners (two V800 and two 10000XL) and the uncertainty analysis is carried out with the four images. RESULTS: The dose estimates of single-channel and multichannel algorithms show a Gaussian behavior and low bias. The multichannel algorithms lead to less uncertainty in the final dose estimates when the EPSON V800 is employed as reading device. In the case of the EPSON 10000XL, the single-channel algorithms provide less uncertainty in the dose estimates for doses higher than four Gy. CONCLUSION: A multi-stage model has been presented. With the aid of this model and the use of the Monte-Carlo techniques, the uncertainty of dose estimates for single-channel and multichannel algorithms are estimated. The application of the model together with Monte-Carlo techniques leads to a complete characterization of the uncertainties in radiochromic film dosimetry.

On the re-calibration process in radiochromic film dosimetry.

PURPOSE: The accuracy and precision of the dose estimates obtained with radiochromic film dosimetry are investigated in a clinical environment. The improvement in the accuracy of dose estimates reached with corrective methods is analyzed. Two novel re-calibration algorithms for radiochromic film dosimetry are presented. METHODS: Two different EBT3 lots are evaluated in two different centres. They are calibrated in Varian linacs and read in two different EPSON scaners. Once the lots are calibrated, three films per lot are considered and divided into stripes that are exposed to known doses. Several dosimetry protocols usually employed in radiochromic film dosimetry are used to convert film responses to absorbed doses. These protocols are characterized by different choices of the film responses or different sensitometric curves. Finally, the accuracy and reproducibility of the dose estimates is investigated with and without the corrective methods. RESULTS AND CONCLUSIONS: The variabilities that affect radiochromic film dosimetry, such as intra-lot variability, inter-scan variability, post-exposure time and film autodevelopment may give rise to inaccuracies in the dose estimates. However, the implementation of re-calibration methods leads to more accurate dose estimates. All the investigated protocols showed more accurate and reproducible results when the re-calibrated methods were employed. So, the novel re-calibration methods may be applied in order to improve the accuracy and reproducibility of radiochromic film dosimetry.

The incidence of the different sources of noise on the uncertainty in radiochromic film dosimetry using single channel and multichannel methods.

The influence of the various sources of noise on the uncertainty in radiochromic film (RCF) dosimetry using single channel and multichannel methods is investigated in this work. These sources of noise are extracted from pixel value (PV) readings and dose maps. Pieces of an RCF were each irradiated to different uniform doses, ranging from 0 to 1092 cGy. Then, the pieces were read at two resolutions (72 and 150 ppp) with two flatbed scanners: Epson 10000XL and Epson V800, representing two states of technology. Noise was extracted as described in ISO 15739 (2013), separating its distinct constituents: random noise and fixed pattern (FP) noise. Regarding the PV maps, FP noise is the main source of noise for both models of digitizer. Also, the standard deviation of the random noise in the 10000XL model is almost twice that of the V800 model. In the dose maps, the FP noise is smaller in the multichannel method than in the single channel ones. However, random noise is higher in this method, throughout the dose range. In the multichannel method, FP noise is reduced, as a consequence of this method's ability to eliminate channel independent perturbations. However, the random noise increases, because the dose is calculated as a linear combination of the doses obtained by the single channel methods. The values of the coefficients of this linear combination are obtained in the present study, and the root of the sum of their squares is shown to range between [Formula: see text] and [Formula: see text] over the dose range studied. These results indicate the random noise to play a fundamental role in the uncertainty of RCF dosimetry: low levels of random noise are required in the digitizer to fully exploit the advantages of the multichannel dosimetry method. This is particularly important for measuring high doses at high spatial resolutions.

Commissioning of the tongue-and-groove modelling in treatment planning systems: from static fields to VMAT treatments.

Adequate modelling of the multi-leaf collimator (MLC) by treatment planning systems (TPS) is essential for accurate dose calculations in intensity-modulated radiation-therapy. For this reason modern TPSs incorporate MLC characteristics such as the leaf end curvature, MLC transmission and the tongue-and-groove. However, the modelling of the tongue-and-groove is often neglected during TPS commissioning and it is not known how accurate it is. This study evaluates the dosimetric consequences of the tongue-and-groove effect for two different MLC models using both film dosimetry and ionisation chambers. A set of comprehensive tests are presented that evaluate the ability of TPSs to accurately model this effect in (a) static fields, (b) sliding window beams and (c) VMAT arcs. The tests proposed are useful for the commissioning of TPSs and for the validation of major upgrades. With the ECLIPSE TPS, relevant differences were found between calculations and measurements for beams with dynamic MLCs in the presence of the TG effect, especially for the High Definition MLC, small gap sizes and the 1 mm calculation grid. For this combination, dose differences as high as 10% and 7% were obtained for dynamic MLC gaps of 5 mm and 10 mm, respectively. These differences indicate inadequate modelling of the tongue-and-groove effect, which might not be identified without the proposed tests. In particular, the TPS tended to underestimate the calculated dose, which may require tuning of other configuration parameters in the TPS (such as the dosimetric leaf gap) in order to maximise the agreement between calculations and measurements in clinical plans. In conclusion, a need for better modelling of the MLC by TPSs is demonstrated, one of the relevant aspects being the tongue-and-groove effect. This would improve the accuracy of TPS calculations, especially for plans using small MLC gaps, such as plans with small target volumes or high complexities. Improved modelling of the MLC would also reduce the need for tuning parameters in the TPS, facilitating a more comprehensive configuration and commissioning of TPSs.

Characterization of noise and digitizer response variability in radiochromic film dosimetry. Impact on treatment verification.

PURPOSE: To study how noise and scanner response variability affect radiochromic film dosimetry. METHODS: Five treatment plans were analyzed in this work with two different multichannel protocols: the multichannel algorithm of Mayer et al. and the efficient protocol of Lewis et al. RESULTS AND CONCLUSION: The multichannel protocol of Mayer et al. is not able to compensate variability in scanner response, which is an important issue for radiochromic film dosimetry. The efficient protocol compensates variations of scanner response, so dose values and gamma scores become more accurate and reproducible. The compensation of digitizer scan variability of the efficient protocol, together with time averaging improve radiochromic film dosimetry. Noise is related to selected resolution in the scanner, our results show that if high resolution measurements are required, de-noising should be considered.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

PURPOSE: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. METHODS: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. RESULTS: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. CONCLUSIONS: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

Small fields measurements with radiochromic films.

The small fields in radiotherapy are widely used due to the development of techniques such as intensity-modulated radiotherapy and stereotactic radio surgery. The measurement of the dose distributions for small fields is a challenge. A perfect dosimeter should be independent of the radiation energy and the dose rate and should have a negligible volume effect. The radiochromic (RC) film characteristics fit well to these requirements. However, the response of RC films and their digitizing processes present a significant spatial inhomogeneity problem. The present work uses a method for two-dimensional (2D) measurement with RC films based on the reduction of the spatial inhomogeneity of both the film and the film digitizing process. By means of registering and averaging several measurements of the same field, the inhomogeneities are mostly canceled. Measurements of output factors (OFs), dose profiles (in-plane and cross-plane), and 2D dose distributions are presented. The field sizes investigated are 0.5 × 0.5 cm(2), 0.7 × 0.7 cm(2), 1 × 1 cm(2), 2 × 2 cm(2), 3 × 3 cm(2), 6 × 6 cm(2), and 10 × 10 cm(2) for 6 and 15 MV photon beams. The OFs measured with the RC film are compared with the measurements carried out with a PinPoint ionization chamber (IC) and a Semiflex IC, while the measured transversal dose profiles were compared with Monte Carlo simulations. The results obtained for the OFs measurements show a good agreement with the values obtained from RC films and the PinPoint and Semiflex chambers when the field size is greater or equal than 2 × 2 cm(2). These agreements give confidence on the accuracy of the method as well as on the results obtained for smaller fields. Also, good agreement was found between the measured profiles and the Monte Carlo calculated profiles for the field size of 1 × 1 cm(2). We expect, therefore, that the presented method can be used to perform accurate measurements of small fields.