A probability model for anatomical robust optimisation in head and neck cancer proton therapy.

Objective.Develop an anatomical model based on the statistics of the population data and evaluate the model for anatomical robust optimisation in head and neck cancer proton therapy.Approach.Deformable image registration was used to build the probability model (PM) that captured the major deformation from patient population data and quantified the probability of each deformation. A cohort of 20 nasopharynx patients was included in this retrospective study. Each patient had a planning CT and 6 weekly CTs during radiotherapy. We applied the model to 5 test patients. Each test patient used the remaining 19 training patients to build the PM and estimate the likelihood of a certain anatomical deformation to happen. For each test patient, a spot scanning proton plan was created. The PM was evaluated using proton spot location deviation and dose distribution.Main results. Using the proton spot range, the PM can simulate small non-rigid variations in the first treatment week within 0.21 ± 0.13 mm. For overall anatomical uncertainty prediction, the PM can reduce anatomical uncertainty from 4.47 ± 1.23 mm (no model) to 1.49 ± 1.08 mm at week 6. The 95% confidence interval (CI) of dose metric variations caused by actual anatomical deformations in the first week is -0.59% ∼ -0.31% for low-risk CTD95, and 0.84-3.04 Gy for parotidDmean. On the other hand, the 95% CI of dose metric variations simulated by the PM at the first week is -0.52 ∼ -0.34% for low-risk CTVD95, and 0.58 ∼ 2.22 Gy for parotidDmean.Significance.The PM improves the estimation accuracy of anatomical uncertainty compared to the previous models and does not depend on the acquisition of the weekly CTs during the treatment. We also provided a solution to quantify the probability of an anatomical deformation. The potential of the model for anatomical robust optimisation is discussed.

Pre-treatment analysis of non-rigid variations can assist robust intensity-modulated proton therapy plan selection for head and neck patients.

PURPOSE: To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans. METHODS: A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT. RESULTS: Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D mean $_{\text{mean}}$ ) of parotid 11.87 Gy, increase in max dose (D max $_{\text{max}}$ ) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D mean $_{\text{mean}}$ by 4.88 Gy, increase in brainstem D max $_{\text{max}}$ by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-risk CTV. CONCLUSION: This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.

Improving workflow for adaptive proton therapy with predictive anatomical modelling: A proof of concept.

PURPOSE: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer. METHODS: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model. Predicted CTs were used to create predicted adaptive plans in advance with the aim of maintaining clinically acceptable dosimetry. Adaption was triggered when the increase in mean dose (Dmean) to the parotid glands exceeded 3 Gy(RBE). We compared the accumulated dose of two adaptive IMPT strategies: 1) Predicted plan adaption: One adaptive plan per patient was optimised on a predicted CT triggered by replan criteria. 2) Standard replan: One adaptive plan was created reactively in response to the triggering weekly CT. RESULTS: Statistical analysis demonstrates that the accumulated dose differences between two adaptive strategies are not significant (p > 0.05) for CTVs and OARs. We observed no meaningful differences in D95 between the accumulated dose and the planned dose for the CTVs, with mean differences to the high-risk CTV of -1.20 %, -1.23 % and -1.25 % for no adaption, standard and predicted plan adaption, respectively. The accumulated parotid Dmean using predicted plan adaption is within 3 Gy(RBE) of the planned dose and 0.31 Gy(RBE) lower than the standard replan approach on average. CONCLUSION: Prediction-based replanning could potentially enable adaptive therapy to be delivered without treatment gaps or sub-optimal fractions, as can occur during a standard replanning strategy, though the benefit of using predicted plan adaption over the standard replan was not shown to be statistically significant with respect to accumulated dose in this study. Nonetheless, a predictive replan approach can offer advantages in improving clinical workflow efficiency.

DIR-based models to predict weekly anatomical changes in head and neck cancer proton therapy.

Objective. We proposed two anatomical models for head and neck patients to predict anatomical changes during the course of radiotherapy.Approach. Deformable image registration was used to build two anatomical models: (1) the average model (AM) simulated systematic progressive changes across the patient cohort; (2) the refined individual model (RIM) used a patient's CT images acquired during treatment to update the prediction for each individual patient. Planning CTs and weekly CTs were used from 20 nasopharynx patients. This dataset included 15 training patients and 5 test patients. For each test patient, a spot scanning proton plan was created. Models were evaluated using CT number differences, contours, proton spot location deviations and dose distributions.Main results. If no model was used, the CT number difference between the planning CT and the repeat CT at week 6 of treatment was on average 128.9 Hounsfield Units (HU) over the test population. This can be reduced to 115.5 HU using the AM, and to 110.5 HU using the RIM3(RIM, updated at week (3). When the predicted contours from the models were used, the average mean surface distance of parotid glands can be reduced from 1.98 (no model) to 1.16 mm (AM) and 1.19 mm (RIM3) at week 6. Using the proton spot range, the average anatomical uncertainty over the test population reduced from 4.47 ± 1.23 (no model) to 2.41 ± 1.12 mm (AM), and 1.89 ± 0.96 mm (RIM3). Based on the gamma analysis, the average gamma index over the test patients was improved from 93.87 ± 2.48 % (no model) to 96.16 ± 1.84% (RIM3) at week 6.Significance. The AM and the RIM both demonstrated the ability to predict anatomical changes during the treatment. The RIM can gradually refine the prediction of anatomical changes based on the AM. The proton beam spots provided an accurate and effective way for uncertainty evaluation.

Experimental comparison of photon versus particle computed tomography to predict tissue relative stopping powers.

PURPOSE: Measurements comparing relative stopping power (RSP) accuracy of state-of-the-art systems representing single-energy and dual-energy computed tomography (SECT/DECT) with proton CT (pCT) and helium CT (HeCT) in biological tissue samples. METHODS: We used 16 porcine and bovine samples of various tissue types and water, covering an RSP range from 0.90 ± 0.06 to 1.78 ± 0.05. Samples were packed and sealed into 3D-printed cylinders ( d = 2  cm, h = 5  cm) and inserted into an in-house designed cylindrical polymethyl methacrylate (PMMA) phantom ( d = 10  cm, h = 10  cm). We scanned the phantom in a commercial SECT and DECT (120 kV; 100  and 140 kV/Sn (tin-filtered)); and acquired pCT and HeCT ( E ∼ 200  MeV/u, 2 ∘ steps, ∼ 6.2 × 10 6 (p)/ ∼ 2.3 × 10 6 (He) particles/projection) with a particle imaging prototype. RSP maps were calculated from SECT/DECT using stoichiometric methods and from pCT/HeCT using the DROP-TVS algorithm. We estimated the average RSP of each tissue per modality in cylindrical volumes of interest and compared it to ground truth RSP taken from peak-detection measurements. RESULTS: Throughout all samples, we observe the following root-mean-squared RSP prediction errors ± combined uncertainty from reference measurement and imaging: SECT 3.10 ± 2.88%, DECT 0.75 ± 2.80%, pCT 1.19 ± 2.81%, and HeCT 0.78 ± 2.81%. The largest mean errors ± combined uncertainty per modality are SECT 8.22 ± 2.79% in cortical bone, DECT 1.74 ± 2.00% in back fat, pCT 1.80 ± 4.27% in bone marrow, and HeCT 1.37 ± 4.25% in bone marrow. Ring artifacts were observed in both pCT and HeCT reconstructions, imposing a systematic shift to predicted RSPs. CONCLUSION: Comparing state-of-the-art SECT/DECT technology and a pCT/HeCT prototype, DECT provided the most accurate RSP prediction, closely followed by particle imaging. The novel modalities pCT and HeCT have the potential to further improve on RSP accuracies with work focusing on the origin and correction of ring artifacts. Future work will study accuracy of proton treatment plans using RSP maps from investigated imaging modalities.

Assessment of the impact of CT calibration procedures for proton therapy planning on pediatric treatments.

PURPOSE: Relative stopping powers (RSPs) for proton therapy are estimated using single-energy computed tomography (SECT), calibrated with standardized tissues of the adult male. It is assumed that those tissues are representative of tissues of all age and sex. Female, male, and pediatric tissues differ from one another in density and composition. In this study, we use tabulated pediatric tissues and computational phantoms to investigate the impact of this assumption on pediatric proton therapy. The potential of dual-energy CT (DECT) to improve the accuracy of these calculations is explored. METHODS: We study 51 human body tissues, categorized into male/female for the age groups newborn, 1-, 5-, 10-, and 15-year-old children, and adult, with given compositions and densities. CT numbers are simulated and RSPs are estimated using SECT and DECT methods. Estimated tissue RSPs from each method are compared to theoretical RSPs. The dose and range errors of each approach are evaluated on three computational phantoms (Ewing's sarcoma, salivary sarcoma, and glioma) derived from pediatric proton therapy patients. RESULTS: With SECT, soft tissues have mean estimation errors and standard deviation up to (1.96 ± 4.18)% observed in newborns, compared to (0.20 ± 1.15)% in adult males. Mean estimation errors for bones are up to (-3.35 ± 4.76)% in pediatrics as opposed to (0.10 ± 0.66)% in adult males. With DECT, mean errors reduce to (0.17 ± 0.13)% and (0.23 ± 0.22)% in newborns (soft tissues/bones). With SECT, dose errors in a Ewing's sarcoma phantom are exceeding 5 Gy (10% of prescribed dose) at the distal end of the treatment field, with volumes of dose errors >5 Gy of V diff > 5 = 4630.7  mm3 . Similar observations are made in the head and neck phantoms, with overdoses to healthy tissue exceeding 2 Gy (4%). A systematic Bragg peak shift resulting in either over- or underdosage of healthy tissues and target volumes depending on the crossed tissues RSP prediction errors is observed. Water equivalent range errors of single beams are between -1.53 and 5.50 mm (min, max) (Ewing's sarcoma phantom), -0.78 and 3.62 mm (salivary sarcoma phantom), and -0.43 and 1.41 mm (glioma phantom). DECT can reduce dose errors to <1 Gy and range errors to <1 mm. CONCLUSION: Single-energy computed tomography estimates RSPs for pediatric tissues with systematic shifts. DECT improves the accuracy of RSPs and dose distributions in pediatric tissues compared to the SECT calibration curve based on adult male tissues.

Statistical limitations in ion imaging.

In this study, we investigated the capacity of various ion beams available for radiotherapy to produce high quality relative stopping power map acquired from energy-loss measurements. The image quality metrics chosen to compare the different ions were signal-to-noise ratio (SNR) as a function of dose and spatial resolution. Geant4 Monte Carlo simulations were performed for: hydrogen, helium, lithium, boron and carbon ion beams crossing a 20 cm diameter water phantom to determine SNR and spatial resolution. It has been found that protons possess a significantly larger SNR when compared with other ions at a fixed range (up to 36% higher than helium) due to the proton nuclear stability and low dose per primary. However, it also yields the lowest spatial resolution against all other ions, with a resolution lowered by a factor 4 compared to that of carbon imaging, for a beam with the same initial range. When comparing for a fixed spatial resolution of 10 lp cm-1, carbon ions produce the highest image quality metrics with proton ions producing the lowest. In conclusion, it has been found that no ion can maximize all image quality metrics simultaneously and that a choice must be made between spatial resolution, SNR, and dose.

Electron density and effective atomic number estimation in a maximum a posteriori framework for dual-energy computed tomography.

PURPOSE: The stoichiometric calibration method for dual-energy CT (DECT) proposed by Bourque et al. (Phys Med Biol. 59:2059; 2014), which provides estimators of the electron density and the effective atomic number, is adapted to a maximum a posteriori (MAP) framework to increase the model's robustness to noise and biases in CT data, specifically for human tissues. Robust physical parameter estimation from noisy DECT scans is required to maximize the precision of quantities used for radiotherapy treatment planning such as the proton stopping power (SPR). METHODS: Estimation of electron density and effective atomic number is performed by constraining their variation to the natural range of values expected for human tissues, while maximizing attenuation data fidelity. The MAP framework is first compared against the original method using theoretical CT numbers with Gaussian noise. The quantitative accuracy of the MAP framework is then validated experimentally on the Gammex 467 phantom. Then, using two clinical datasets, the advantages of the approach are experimentally evaluated, qualitatively, and quantitatively. RESULTS: The theoretical study shows that the root-mean-square error on the electron density, the effective atomic number and the SPR are, respectively, reduced from 2.3 to 1.5, 5.7 to 3.2 and 2.8 to 1.7% with the adapted framework, when analyzing soft tissues and bone together. The experimental validation study shows that the standard deviation in Gammex inserts can be reduced, on average, by factors of 1.4 (electron density), 2.7 (effective atomic number), and 1.9 (SPR), while the quantitative accuracy of the three physical parameters is preserved, on average. Evaluation on clinical datasets show apparent noise reduction in maps of all estimated physical quantities, and suggests that the MAP framework has increased robustness to beam hardening and photon starvation artifacts. Mean values for the electron density, the effective atomic number, and the SPR averaged in four uniform regions of interest (brain, muscle, adipose, and cranium), respectively, differ by 0.7, 1.8, and 0.9% between both frameworks. The standard deviation in the same regions of interest is also reduced, on average, by factors of 1.8, 6.6, and 3.2 with the MAP framework. Differences in mean value and standard deviations are statistically significant. CONCLUSION: Theoretical and experimental results suggest that the MAP framework produces more accurate and precise estimates of the electron density and SPR. Thus, the present approach limits the propagation of noise in DECT attenuation data to radiotherapy-related parameters maps such as the SPR and the electron density. Using a MAP framework with DECT for radiotherapy treatment planning can help maximizing the precision of dose calculation. The method also provides more precise estimates of the effective atomic number. The MAP methodology is presented in a general way such that it can be adapted to any DECT image-based tissue characterization method.

The impact of dual- and multi-energy CT on proton pencil beam range uncertainties: a Monte Carlo study.

The purpose of this work is to evaluate the impact of single-, dual- and multi-energy CT (SECT, DECT and MECT) on proton range uncertainties in a patient like geometry and a full Monte Carlo environment. A virtual patient is generated from a real patient pelvis CT scan, where known mass densities and elemental compositions are overwritten in each voxel. Simulated CT images for SECT, DECT and MECT are generated for two limiting cases: (1) theoretical and idealistic CT numbers only affected by Gaussian noise (case A, the best scenario) and (2) reconstructed polyenergetic sinograms containing beam hardening, projection-based Poisson noise, and reconstruction artifacts (case B, the worst scenario). Conversion of the simulated SECT images into Monte Carlo inputs is done following the stoichiometric calibration method. For DECT and MECT, the Bayesian eigentissue decomposition method of Lalonde (2017 Med. Phys. 44 5293-302) is used. Pencil beams from seven different angles around the virtual patient are simulated using TOPAS to assess the performance of each method. Percentage depth doses curves (PDD) are compared to ground truth in order to determine the accuracy of range prediction of each imaging modality. For the idealistic images of case A, MECT and DECT slightly outperforms SECT. Root mean square (RMS) errors or 0.78 mm, 0.49 mm and 0.42 mm on R 80 mm, are observed for SECT, DECT and MECT respectively. In case B, PDD calculated in the MECT derived Monte Carlo inputs generally shows the best agreement with ground truth in both shape and position, with RMS errors of 2.03 mm, 1.38 mm and 0.86 mm for SECT, DECT and MECT respectively. Overall, the Bayesian eigentissue decomposition used with DECT systematically predicts proton ranges more accurately than the gold standard SECT-based approach. When CT numbers are severely affected by imaging artifacts, MECT with four energy bins becomes more reliable than both DECT and SECT.

Optimized I-values for use with the Bragg additivity rule and their impact on proton stopping power and range uncertainty.

Novel imaging modalities can improve the estimation of patient elemental compositions for particle treatment planning. The mean excitation energy (I-value) is a main contributor to the proton range uncertainty. To minimize their impact on beam range errors and quantify their uncertainties, the currently used I-values proposed in 1982 are revisited. The study aims at proposing a new set of optimized elemental I-values for use with the Bragg additivity rule (BAR) and establishing uncertainties on the optimized I-values and the BAR. We optimize elemental I-values for the use in compounds based on measured material I-values. We gain a new set of elemental I-values and corresponding uncertainties, based on the experimental uncertainties and our uncertainty model. We evaluate uncertainties on I-values and relative stopping powers (RSP) of 70 human tissues, taking into account statistical correlations between tissues and water. The effect of new I-values on proton beam ranges is quantified using Monte Carlo simulations. Our elemental I-values describe measured material I-values with higher accuracy than ICRU-recommended I-values (RMSE: 6.17% (ICRU), 5.19% (this work)). Our uncertainty model estimates an uncertainty component from the BAR to 4.42%. Using our elemental I-values, we calculate the I-value of water as 78.73 ± 2.89 eV, being consistent with ICRU 90 (78 ± 2 eV). We observe uncertainties on tissue I-values between 1.82-3.38 eV, and RSP uncertainties between 0.002%-0.44%. With transport simulations of a proton beam in human tissues, we observe range uncertainties between 0.31% and 0.47%, as compared to current estimates of 1.5%. We propose a set of elemental I-values well suited for human tissues in combination with the BAR. Our model establishes uncertainties on elemental I-values and the BAR, enabling to quantify uncertainties on tissue I-values, RSP as well as particle range. This work is particularly relevant for Monte Carlo simulations where the interaction probabilities are reconstructed from elemental compositions.

Experimental validation of two dual-energy CT methods for proton therapy using heterogeneous tissue samples.

PURPOSE: The purpose of this work is to evaluate the performance of dual-energy CT (DECT) for determining proton stopping power ratios (SPRs) in an experimental environment and to demonstrate its potential advantages over conventional single-energy CT (SECT) in clinical conditions. METHODS: Water equivalent range (WER) measurements of 12 tissue-equivalent plastic materials and 12 fresh animal tissue samples are performed in a 195 MeV broad proton beam using the dose extinction method. SECT and DECT scans of the samples are performed with a dual-source CT scanner (Siemens SOMATOM Definition Flash). The methods of Schneider et al. (1996), Bourque et al. (2014), and Lalonde et al. (2017) are used to predict proton SPR on SECT and DECT images. From predicted SPR values, the WER of the proton beam through the sample is predicted for SECT and DECT using Monte Carlo simulations and compared to the measured WER. RESULTS: For homogeneous tissue-equivalent plastic materials, results with DECT are consistent with experimental measurements and show a systematic reduction of SPR uncertainty compared to SECT, with root-mean-square errors of 1.59% versus 0.61% for SECT and DECT, respectively. Measurements with heterogeneous animal samples show a clear reduction of the bias on range predictions in the presence of bones, with -0.88% for SECT versus -0.58% and -0.14% for both DECT methods. An uncertainty budget allows isolating the effect of CT number conversion to SPR and predicts improvements by DECT over SECT consistently with theoretical predictions, with 0.34% and 0.31% for soft tissues and bones in the experimental setup compared to 0.34% and 1.14% with the theoretical method. CONCLUSIONS: The present work uses experimental measurements in a realistic clinical environment to show potential benefits of DECT for proton therapy treatment planning. Our results show clear improvements over SECT in tissue-equivalent plastic materials and animal tissues. Further work towards using Monte Carlo simulations for treatment planning with DECT data and a more detailed investigation of the uncertainties on I-value and limitations on the Bragg additivity rule could potentially further enhance the benefits of this imaging technology for proton therapy.

Extension of the Fermi-Eyges most-likely path in heterogeneous medium with prior knowledge information.

Particle imaging suffers from poor spatial resolution due to the multiple Coulomb scattering deflections undergone by the particles throughout their path. To account for these deflections, a most-likely path (MLP) formalism was developed based on a Bayesian adaption of the Fermi-Eyges theory. Previous work calculated the MLP formalism in a homogeneous water medium as an initial estimate. However, this potentially reduces the accuracy of the MLP estimate as well as the achievable resolution of the subsequent tomographic reconstruction. This work investigates the potential gain of introducing prior-knowledge on the medium composition and density to improve the MLP accuracy. To do so, a Monte Carlo (MC) Geant4 algorithm was used to simulate protons ([Formula: see text]) crossing three different anthropomorphic phantoms representing the lung, abdomen, and head. The prior-knowledge information is gathered from (1) the MC simulation for ground-truth (MLP-GT), or from (2) a recent DECT material decomposition technique (MLP-DECT). The reconstructed path accuracy using prior-knowledge methods is compared with (3) the path reconstructed in homogeneous water (MLP-Water) and (4) a path reconstruction method where the proton path is projected onto a Hull at the boundary of the phantom with a subsequent MLP-Water calculation (MLP-Hull). For each path reconstruction method, the maximal root-mean-square error (RMSmax) is compared between the reconstructed and the MC path. In every phantom, the RMSmax is decreased between the MLP-Water and the three other path algorithms that take into account heterogeneities ([Formula: see text] for the lung, [Formula: see text] for the abdomen and [Formula: see text] for the head), with no significant differences between each (MLP-DECT, MLP-GT and MLP-Hull). In conclusion, the introduction of prior-knowledge in the MLP formalism decreases the RMS uncertainty to the MC path, but no further than the use of a simpler Hull contour algorithm. The use of this Hull algorithm is suggested for future particle imaging applications.

A Bayesian approach to solve proton stopping powers from noisy multi-energy CT data.

PURPOSE: To propose a new formalism allowing the characterization of human tissues from multienergy computed tomography (MECT) data affected by noise and to evaluate its performance in estimating proton stopping powers (SPR). METHODS: A recently published formalism based on principal component analysis called eigentissue decomposition (ETD) is adapted to the context of noise using a Bayesian estimator. The method, named Bayesian ETD, uses the maximum a posteriori fractions of eigentissues in each voxel to determine physical parameters relevant for proton beam dose calculation. Simulated dual-energy computed tomography (DECT) data are used to evaluate the performance of the proposed method to estimate SPR and to compare it to the initially proposed maximum-likelihood ETD and to a state-of-the-art ρe  - Z formalism. To test the robustness of each method towards clinical reality, three different levels of noise are implemented, as well as variations in elemental composition and density of reference tissues. The impact of using more than two energy bins to determine SPR is also investigated by simulating MECT data using two to five energy bins. Finally, the impact of using MECT over DECT for range prediction is evaluated using a probabilistic model. RESULTS: For simulated DECT data of reference tissues, the Bayesian ETD approach systematically gives lower root-mean-square (RMS) errors with negligible bias. For a medium level of noise, the RMS errors on SPR are found to be 2.78%, 2.76% and 1.53% for ρe  - Z, maximum-likelihood ETD, and Bayesian ETD, respectively. When variations are introduced to the elemental composition and density, all implemented methods give similar performances at low noise. However, for a medium noise level, the proposed Bayesian method outperforms the two others with a RMS error of 1.94%, compared to 2.79% and 2.78% for ρe  - Z and maximum-likelihood ETD, respectively. When more than two energy spectra are used, the Bayesian ETD is able to reduce RMS error on SPR using up to five energy bins. In terms of range prediction, Bayesian ETD with four energy bins in realistic conditions reduces proton beam range uncertainties by a factor of up to 1.5 compared to ρe  - Z. CONCLUSION: The Bayesian ETD is shown to be more robust against noise than similar methods and a promising approach to extract SPR from noisy DECT data. In the advent of commercially available multi-energy CT or photon-counting CT scanners, the Bayesian ETD is expected to allow extracting more information and improve the precision of proton therapy beyond DECT.

The potential of dual-energy CT to reduce proton beam range uncertainties.

PURPOSE: Dual-energy CT (DECT) promises improvements in estimating stopping power ratios (SPRs) for proton therapy treatment planning. Although several comparable mathematical formalisms have been proposed in literature, the optimal techniques to characterize human tissue SPRs with DECT in a clinical environment are not fully established. The aim of this work is to compare the most robust DECT methods against conventional single-energy CT (SECT) in conditions reproducing a clinical environment, where CT artifacts and noise play a major role on the accuracy of these techniques. METHODS: Available DECT tissue characterization methods are investigated and their ability to predict SPRs is compared in three contexts: (a) a theoretical environment using the XCOM cross section database; (b) experimental data using a dual-source CT scanner on a calibration phantom; (c) simulations of a virtual humanoid phantom with the ImaSim software. The latter comparison accounts for uncertainties caused by CT artifacts and noise, but leaves aside other sources of uncertainties such as CT grid size and the I-values. To evaluate the clinical impact, a beam range calculation model is used to predict errors from the probability distribution functions determined with ImaSim simulations. Range errors caused by SPR errors in soft tissues and bones are investigated. RESULTS: Range error estimations demonstrate that DECT has the potential of reducing proton beam range uncertainties by 0.4% in soft tissues using low noise levels of 12 and 8 HU in DECT, corresponding to 7 HU in SECT. For range uncertainties caused by the transport of protons through bones, the reduction in range uncertainties for the same levels of noise is found to be up to 0.6 to 1.1 mm for bone thicknesses ranging from 1 to 5 cm, respectively. We also show that for double the amount noise, i.e., 14 HU in SECT and 24 and 16 HU for DECT, the advantages of DECT in soft tissues are lost over SECT. In bones however, the reduction in range uncertainties is found to be between 0.5 and 0.9 mm for bone thicknesses ranging from 1 to 5 cm, respectively. CONCLUSION: DECT has a clear potential to improve proton beam range predictions over SECT in proton therapy. However, in the current state high levels of noise remain problematic for DECT characterization methods and do not allow getting the full benefits of this technology. Future work should focus on adapting DECT methods to noise and investigate methods based on raw-data to reduce CT artifacts.

The application of metal artifact reduction (MAR) in CT scans for radiation oncology by monoenergetic extrapolation with a DECT scanner.

Metal artifacts in computed tomography CT images are one of the main problems in radiation oncology as they introduce uncertainties to target and organ at risk delineation as well as dose calculation. This study is devoted to metal artifact reduction (MAR) based on the monoenergetic extrapolation of a dual energy CT (DECT) dataset. In a phantom study the CT artifacts caused by metals with different densities: aluminum (ρ Al=2.7 g/cm(3)), titanium (ρ Ti=4.5 g/cm(3)), steel (ρ steel=7.9 g/cm(3)) and tungsten (ρ W=19.3g/cm(3)) have been investigated. Data were collected using a clinical dual source dual energy CT (DECT) scanner (Siemens Sector Healthcare, Forchheim, Germany) with tube voltages of 100 kV and 140 kV(Sn). For each tube voltage the data set in a given volume was reconstructed. Based on these two data sets a voxel by voxel linear combination was performed to obtain the monoenergetic data sets. The results were evaluated regarding the optical properties of the images as well as the CT values (HU) and the dosimetric consequences in computed treatment plans. A data set without metal substitute served as the reference. Also, a head and neck patient with dental fillings (amalgam ρ=10 g/cm(3)) was scanned with a single energy CT (SECT) protocol and a DECT protocol. The monoenergetic extrapolation was performed as described above and evaluated in the same way. Visual assessment of all data shows minor reductions of artifacts in the images with aluminum and titanium at a monoenergy of 105 keV. As expected, the higher the densities the more distinctive are the artifacts. For metals with higher densities such as steel or tungsten, no artifact reduction has been achieved. Likewise in the CT values, no improvement by use of the monoenergetic extrapolation can be detected. The dose was evaluated at a point 7 cm behind the isocenter of a static field. Small improvements (around 1%) can be seen with 105 keV. However, the dose uncertainty remains of the order of 10% to 20%. Thus, the improvement is not significant for radiotherapy planning. For amalgam with a density between steel and tungsten, monoenergetic data sets of a patient do not show substantial artifact reduction. The local dose uncertainties around the metal artifact determined for a static field are of the order of 5%. Although dental fillings are smaller than the phantom inserts, metal artifacts could not be reduced effectively. In conclusion, the image based monoenergetic extrapolation method does not provide efficient reduction of the consequences of CT-generated metal artifacts for radiation therapy planning, but the suitability of other MAR methods will be subsequently studied.