Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Proton beam dosimetry in the presence of magnetic fields using Farmer-type ionization chambers of different radii.

BACKGROUND: Magnetic resonance-guided proton therapy is promising, as it combines high-contrast imaging of soft tissue with highly conformal dose delivery. However, proton dosimetry in magnetic fields using ionization chambers is challenging since the dose distribution as well as the detector response are perturbed. PURPOSE: This work investigates the effect of the magnetic field on the ionization chamber response, and on the polarity and ion recombination correction factors, which are essential for the implementation of a proton beam dosimetry protocol in the presence of magnetic fields. METHODS: Three Farmer-type cylindrical ionization chambers, the 30013 with 3 mm inner radius (PTW, Freiburg, Germany) and two custom built chambers "R1" and "R6" with 1 and 6 mm inner radii respectively were placed at the center of an experimental electromagnet (Schwarzbeck Mess - Elektronik, Germany) 2 cm depth of an in-house developed 3D printed water phantom. The detector response was measured for a 3 × 10 cm2 field of mono-energetic protons 221.05 MeV/u for the three chambers, and with an additional proton beam of 157.43 MeV/u for the chamber PTW 30013. The magnetic flux density was varied between 0.1 and 1.0 Tesla in steps of 0.1 Tesla. RESULTS: At both energies, the ionization chamber PTW 30013 showed a non-linear response as a function of the magnetic field strength, with a decrease of the ionization chamber response of up to 0.27% ± 0.06% (1 SD) at 0.2 Tesla, followed by a smaller effect at higher magnetic field strength. For the chamber R1, the response decreased slightly with the magnetic field strength up to 0.45% ± 0.12% at 1 Tesla, and for the chamber R6, the response decreased up to 0.54% ± 0.13% at 0.1 Tesla, followed by a plateau up to 0.3 Tesla, and a weaker effect at higher magnetic field strength. The dependence of the polarity and recombination correction factor on the magnetic field was ⩽0.1% for the chamber PTW 30013. CONCLUSIONS: The magnetic field has a small but significant effect on the chamber response in the low magnetic field region for the chamber PTW 30013 and for R6, and in the high magnetic field region for the chamber R1. Corrections may be necessary for ionization chamber measurements, depending on both the chamber volume and the magnetic flux density. No significant effect of the magnetic field on the polarity and recombination correction factor was detected in this work for the ionization chamber PTW 30013.

Sensitivity correction of fluorescent nuclear track detectors using alpha particles: Determining LET spectra of light ions with enhanced accuracy.

BACKGROUND: Radiation fields encountered in proton therapy (PT) and ion-beam therapy (IBT) are characterized by a variable linear energy transfer (LET), which lead to a variation of relative biological effectiveness and also affect the response of certain dosimeters. Therefore, reliable tools to measure LET are advantageous to predict and correct LET effects. Fluorescent nuclear track detectors (FNTDs) are suitable to measure LET spectra within the range of interest for PT and IBT, but so far the accuracy and precision have been challenged by sensitivity variations between individual crystals. PURPOSE: To develop a novel methodology to correct changes in the fluorescent intensity due to sensitivity variations among FNTDs. This methodology is based on exposing FNTDs to alpha particles in order to derive a detector-specific correction factor. This will allow us to improve the accuracy and precision of LET spectra measurements with FNTDs. METHODS: FNTDs were exposed to alpha particles. Afterward, the detectors were irradiated to monoenergetic protons, 4 He-, 12 C-, and 16 O-ions. At each step, the detectors were imaged with a confocal laser scanning microscope. The tracks were reconstructed and analyzed using in-house developed tools. Alpha-particle tracks were used to derive a detector-specific sensitivity correction factor ( k s , i ${k_{s,i}}$ ). Proton, 4 He-, 12 C-, and 16 O-ion tracks were used to establish a traceable calibration curve that relates the fluorescence intensity with the LET in water ( L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ ). FNTDs from a second batch were exposed and analyzed following the same procedures, to test if k s , i ${k_{s,i}}$ can be used to extend the applicability of the calibration curve to detectors from different batches. Finally, a set of blind tests was performed to assess the accuracy of the proposed methodology without user bias. Throughout all stages, the main sources of uncertainty were evaluated. RESULTS: Based on a sample of 100 FNTDs, our findings show a high sensitivity heterogeneity between FNTDs, with k s , i ${k_{s,i}}$ having values between 0.57 and 2.55. The fitting quality of the calibration curve, characterized by the mean absolute percentage residuals and correlation coefficient, was improved when k s , i ${k_{s,i}}$ was considered. Results for detectors from the second batch show that, if the fluorescence signal is corrected by k s , i ${k_{s,i}}$ , the differences in the predicted L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with respect to the reference set are reduced from 55%, 141%, 41%, and 186% to 4.2%, 6.5%, 5.0%, and 11.0%, for protons, 4 He-, 12 C-, and 16 O-ions, respectively. The blind tests showed that it is possible to measure the track- and dose-average L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with an accuracy of 0.3%, 16%, and 9.6% and 1.7%, 28%, and 30% for protons, 12 C-ions and mixed beams, respectively. On average, the combined uncertainty of the measured L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ was 11%, 13%, 21%, and 26% for protons, 4 He-, 12 C-, and 16 O-ions, respectively. These values were increased by a mean factor of 2.0 when k s , i ${k_{s,i}}$ was not applied. CONCLUSIONS: We have demonstrated for the first time that alpha particles can be used to derive a detector-specific sensitivity correction factor. The proposed methodology allows us to measure LET spectra using FNTD-technology, with a degree of accuracy and precision unreachable before with sole experimental approaches.

Biosensor for deconvolution of individual cell fate in response to ion beam irradiation.

Clonogenic survival assay constitutes the gold standard method for quantifying radiobiological effects. However, it neglects cellular radiation response variability and heterogeneous energy deposition by ion beams on the microscopic scale. We introduce "Cell-Fit-HD4D" a biosensor that enables a deconvolution of individual cell fate in response to the microscopic energy deposition as visualized by optical microscopy. Cell-Fit-HD4D enables single-cell dosimetry in clinically relevant complex radiation fields by correlating microscopic beam parameters with biological endpoints. Decrypting the ion beam's energy deposition and molecular effects at the single-cell level has the potential to improve our understanding of radiobiological dose concepts as well as radiobiological study approaches in general.

Triple channel analysis of Gafchromic EBT3 irradiated with clinical carbon-ion beams.

Self-developing radiochromic film is widely used in radiotherapy QA procedures. To compensate for typical film inhomogeneities, the triple channel analysis method is commonly used for photon-irradiated film. We investigated the applicability of this method for GafchromicTMEBT3 (Ashland) film irradiated with a clinically used carbon-ion beam. Calibration curves were taken from EBT3 film specimens irradiated with monoenergetic carbon-ion beams of different doses. Measurements of the lateral field shape and homogeneity were performed in the middle of a passively modulated spread-out Bragg peak and compared to simultaneous characterization by means of a 2D ionization chamber array. Additional measurements to investigate the applicability of EBT3 for quality assurance (QA) measurement in carbon-ion beams were performed. The triple-channel analysis reduced the relative standard deviation of the doses in a uniform carbon ion field by 30% (from 1.9% to 1.3%) and reduced the maximum deviation by almost a factor of 3 (from 28.6% to 9.8%), demonstrating the elimination of film artifacts. The corrected film signal showed considerably improved image quality and quantitative agreement with the ionization chamber data, thus providing a clear rationale for the usage of the triple channel analysis in carbon-beam QA.

Dosimetry in magnetic fields with dedicated MR-compatible ionization chambers.

MR-integrated radiotherapy requires suitable dosimetry detectors to be used in magnetic fields. This study investigates the feasibility of using dedicated MR-compatible ionization chambers at MR-integrated radiotherapy devices. MR-compatible ionization chambers (Exradin A19MR, A1SLMR, A26MR, A28MR) were precisely modeled and their relative response in a 6MV treatment beam in the presence of a magnetic field was simulated using EGSnrc. Monte Carlo simulations were carried out with the magnetic field in three orientations: the magnetic field aligned perpendicular to the chamber and beam axis (transverse orientation), the magnetic field parallel to the chamber as well as parallel to the beam axis. Monte Carlo simulation results were validated with measurements using an electromagnet with magnetic field strength upto 1.1 T with the chambers in transverse orientation. The measurements and simulation results were in good agreement, except for the A26MR ionization chamber in transverse orientation. The maximum increase in response of the ionization chambers observed was 8.6% for the transverse orientation. No appreciable change in chamber response due to the magnetic field was observed for the magnetic field parallel to the ionization chamber and parallel to the photon beam. Polarity and recombination correction factor were experimentally investigated in the transverse orientation. The polarity effect and recombination effect were not altered by a magnetic field. This study further investigates the response of the ionization chambers as a function of the chambers' rotation around their longitudinal axis. A variation in response was observed when the chamber was not rotationally symmetric, which was independent of the magnetic field.

2D range modulator for high-precision water calorimetry in scanned carbon-ion beams.

Ionization chamber-based dosimetry for carbon-ion beams still shows a significantly higher standard uncertainty than high-energy photon dosimetry. This is mainly caused by the high standard uncertainty of the correction factor for beam quality [Formula: see text]. Due to a lack of experimental data, the given values for [Formula: see text] are based on theoretical calculations. To reduce this standard uncertainty, [Formula: see text] factors for different irradiation conditions and ionization chambers (ICs) can be determined experimentally by means of water calorimetry. To perform such measurements in a spread-out Bragg peak (SOBP) for a scanned carbon-ion beam, we describe the process of creating an almost cubic dose distribution of about 6 × 6 × 6 cm3 using a 2D range modulator. The aim is to achieve a field homogeneity with a standard deviation of measured dose values in the middle of the SOBP (over a lateral range and a depth of about 4 cm) below 2% within a scanning time of under 100 s, applying a dose larger than 1 Gy. This paper describes the optimization and characterization of the dose distribution in detail.

Refinement of the Hounsfield look-up table by retrospective application of patient-specific direct proton stopping-power prediction from dual-energy CT.

BACKGROUND AND PURPOSE: Proton treatment planning relies on an accurate determination of stopping-power ratio (SPR) from x-ray computed tomography (CT). A refinement of the heuristic CT-based SPR prediction using a state-of-the-art Hounsfield look-up table (HLUT) is proposed, which incorporates patient SPR information obtained from dual-energy CT (DECT) in a retrospective patient-cohort analysis. MATERIAL AND METHODS: SPR datasets of 25 brain-tumor patients, 25 prostate-cancer patients, and three nonsmall cell lung-cancer (NSCLC) patients were calculated from clinical DECT scans with the comprehensively validated DirectSPR approach. Based on the median frequency distribution of voxelwise correlations between CT number and SPR within the irradiated volume, a piecewise linear function was specified (DirectSPR-based adapted HLUT). Differences in dose distribution and proton range were assessed for the nonadapted and adapted HLUT in comparison to the DirectSPR method, which has been shown to be an accurate and reliable SPR estimation method. RESULTS: The application of the DirectSPR-based adapted HLUT instead of the nonadapted HLUT reduced the systematic proton range differences from 1.2% (1.1 mm) to -0.1% (0.0 mm) for brain-tumor patients, 1.7% (4.1 mm) to 0.2% (0.5 mm) for prostate-cancer patients, and 2.0% (2.9 mm) to -0.1% (0.0 mm) for NSCLC patients. Due to the large intra- and inter-patient tissue variability, range differences to DirectSPR larger than 1% remained for the adapted HLUT. CONCLUSIONS: The incorporation of patient-specific correlations between CT number and SPR, derived from a retrospective application of DirectSPR to a broad patient cohort, improves the SPR accuracy of the current state-of-the-art HLUT approach. The DirectSPR-based adapted HLUT has been clinically implemented at the University Proton Therapy Dresden (Dresden, Germany) in 2017. This already facilitates the benefits of an improved DECT-based tissue differentiation within clinical routine without changing the general approach for range prediction (HLUT), and represents a further step toward full integration of the DECT-based DirectSPR method for treatment planning in proton therapy.

Analytical modeling of depth-dose degradation in heterogeneous lung tissue for intensity-modulated proton therapy planning.

BACKGROUND AND PURPOSE: Proton therapy may be promising for treating non-small-cell lung cancer due to lower doses to the lung and heart, as compared to photon therapy. A reported challenge is degradation, i.e., a smoothing of the depth-dose distribution due to heterogeneous lung tissue. For pencil beams, this causes a distal falloff widening and a peak-to-plateau ratio decrease, not considered in clinical treatment planning systems. MATERIALS AND METHODS: We present a degradation model implemented into an analytical dose calculation, fully integrated into a treatment planning workflow. Degradation effects were investigated on target dose, distal dose falloffs, and mean lung dose for ten patient cases with varying anatomical characteristics. RESULTS: For patients with pronounced range straggling (in our study large tumors, or lesions close to the mediastinum), degradation effects were restricted to a maximum decrease in target coverage (D 95 of the planning target volume) of 1.4%. The median broadening of the distal 80-20% dose falloffs was 0.5 mm at the maximum. For small target volumes deep inside lung tissue, however, the target underdose increased considerably by up to 26%. The mean lung dose was not negatively affected by degradation in any of the investigated cases. CONCLUSION: For most cases, dose degradation due to heterogeneous lung tissue did not yield critical organ at risk overdosing or overall target underdosing. However, for small and deep-seated tumors which can only be reached by penetrating lung tissue, we have seen substantial local underdose, which deserves further investigation, also considering other prevalent sources of uncertainty.

Isolation of time-dependent DNA damage induced by energetic carbon ions and their fragments using fluorescent nuclear track detectors.

PURPOSE: High energetic carbon (C-) ion beams undergo nuclear interactions with tissue, producing secondary nuclear fragments. Thus, at depth, C-ion beams are composed of a mixture of different particles with different linear energy transfer (LET) values. We developed a technique to enable isolation of DNA damage response (DDR) in mixed radiation fields using beam line microscopy coupled with fluorescence nuclear track detectors (FNTDs). METHODS: We imaged live cells on a coverslip made of FNTDs right after C-ion, proton or photon irradiation using an in-house built confocal microscope placed in the beam path. We used the FNTD to link track traversals with DNA damage and separated DNA damage induced by primary particles from fragments. RESULTS: We were able to spatially link physical parameters of radiation tracks to DDR in live cells to investigate spatiotemporal DDR in multi-ion radiation fields in real time, which was previously not possible. We demonstrated that the response of lesions produced by the high-LET primary particles associates most strongly with cell death in a multi-LET radiation field, and that this association is not seen when analyzing radiation induced foci in aggregate without primary/fragment classification. CONCLUSIONS: We report a new method that uses confocal microscopy in combination with FNTDs to provide submicrometer spatial-resolution measurements of radiation tracks in live cells. Our method facilitates expansion of the radiation-induced DDR research because it can be used in any particle beam line including particle therapy beam lines. CATEGORY: Biological Physics and Response Prediction.

Towards a generalised development of synthetic CT images and assessment of their dosimetric accuracy.

Background: The interest in generating "synthetic computed tomography (CT) images" from magnetic resonance (MR) images has been increasing over the past years due to advances in MR guidance for radiotherapy. A variety of methods for synthetic CT creation have been developed, from simple bulk density assignment to complex machine learning algorithms.Material and methods: In this study, we present a general method to determine simplistic synthetic CTs and evaluate them according to their dosimetric accuracy. It separates the requirements on the MR image and the associated calculation effort to generate a synthetic CT. To evaluate the significance of the dosimetric accuracy under realistic conditions, clinically common uncertainties including position shifts and Hounsfield lookup table (HLUT) errors were simulated. To illustrate our approach, we first translated CT images from a test set of six pelvic cancer patients to relative electron density (ED) via a clinical HLUT. For each patient, seven simplified ED images (simED) were generated at different levels of complexity, ranging from one to four tissue classes. Then, dose distributions optimised on the reference ED image and the simEDs were compared to each other in terms of gamma pass rates (2 mm/2% criteria) and dose volume metrics.Results: For our test set, best results were obtained for simEDs with four tissue classes representing fat, soft tissue, air, and bone. For this simED, gamma pass rates of 99.95% (range: 99.72-100%) were achieved. The decrease in accuracy from ED simplification was smaller in this case than the influence of the uncertainty scenarios on the reference image, both for gamma pass rates and dose volume metrics.Conclusions: The presented workflow helps to determine the required complexity of synthetic CTs with respect to their dosimetric accuracy. The investigated cases showed potential simplifications, based on which the synthetic CT generation could be faster and more reproducible.

Impact of new ICRU 90 key data on stopping-power ratios and beam quality correction factors for carbon ion beams.

The recent update of key dosimetric data by the International Commission on Radiation Units and Measurements (ICRU) makes several changes to the computation of beam quality correction factors k Q with regard to, for example, the mean excitation energies, I, which enter the stopping power computation for water and air, the computation procedure itself, the average energy expended in the production of an ion pair in air, W/e, as well as chamber-specific factors for cobalt-60. With the new recommendations an accurate assessment of the water-to-air stopping-power ratio, [Formula: see text], in reference conditions is necessary to update the dosimetry protocols for carbon ion beams. The ICRU 90 key data were considered for computation of [Formula: see text] for carbon ion beams using Monte Carlo transport simulations for a number of reference conditions, namely monoenergetic carbon ion beams with a range in water from 3 to 30 cm and spread-out Bragg peaks (SOBPs) of different widths and depths in water. New recommendations for [Formula: see text] are presented, namely 1.1247 for the reference condition of depth 1 g cm-2 for monoenergetic carbon ion beams and 1.1273 at the center of physically optimized SOBPs. The recommendation of a constant value (1.126) represents the stopping-power ratio within a 0.3% variation of [Formula: see text] for all reference conditions considered. The impact of these new [Formula: see text] values and the updated key data on k Q for carbon ion beams was evaluated in a second step. Changes and the difference from experimental data were found to be non-significant, but larger discrepancies to measurements were observed for plane-parallel ionization chambers. The combined uncertainty for k Q in carbon ion beams decreased to 2.4%. In future, it could be further lowered by using chamber-specific Monte Carlo transport simulations, for which the implementation of ICRU 90 key data as done in this study is a prerequisite.

Dual-Energy Computed Tomography to Assess Intra- and Inter-Patient Tissue Variability for Proton Treatment Planning of Patients With Brain Tumor.

PURPOSE: Range prediction in particle therapy is associated with an uncertainty originating from calculating the stopping-power ratio (SPR) based on x-ray computed tomography (CT). Here, we assessed the intra- and inter-patient variability of tissue properties in patients with primary brain tumor using dual-energy CT (DECT) and quantified its influence on current SPR prediction. METHODS AND MATERIALS: For 102 patients' DECT scans, SPR distributions were derived from a patient-specific DECT-based approach (DirectSPR). The impact of soft tissue diversity and age-related variations in bone composition on SPR were assessed. Tissue-specific and global deviations between this method and the state-of-the-art CT-number-to-SPR conversion applying a Hounsfield look-up table (HLUT) were quantified. To isolate systematic deviations between the two, the HLUT was also optimized using DECT information. RESULTS: An intra-patient ± inter-patient soft tissue diversity of 5.6% ± 0.7% in SPR (width of 95% confidence interval) was obtained including imaging- and model-related variations of up to 2.9%. This intra-patient SPR variability is associated with a mean absolute SPR deviation of 1.2% between the patient-specific DirectSPR approach and an optimal HLUT. Between adults and children younger than 6 years, age-related variations in bone composition resulted in a median SPR difference of approximately 5%. CONCLUSIONS: Accurate patient-specific DECT-based stopping-power prediction allows for improved handling of tissue mixtures and can intrinsically incorporate most of the SPR variability arising from tissue mixtures as well as inter-patient and intra-tissue variations. Since the state-of-the-art HLUT-even after cohort-specific optimization-cannot fully consider the broad tissue variability, patient-specific DECT-based stopping-power prediction is advisable in particle therapy.

On the equivalence of image-based dual-energy CT methods for the determination of electron density and effective atomic number in radiotherapy.

Dual-energy computed tomography enables the determination of relative electron density and effective atomic number. As this can increase accuracy in radiotherapy treatment planning, a substantial number of algorithms for the determination of the two quantities has been suggested - most of them based on reconstructed CT images. We show that many of these methods share a common theoretical framework. Equations can be transformed from one method to the other by re-definition of the calibration parameters. We suggest that further work should be spent on practical calibration and the reliability of CT numbers rather than on the theoretical framework.

Experimental verification of stopping-power prediction from single- and dual-energy computed tomography in biological tissues.

An experimental setup for consecutive measurement of ion and x-ray absorption in tissue or other materials is introduced. With this setup using a 3D-printed sample container, the reference stopping-power ratio (SPR) of materials can be measured with an uncertainty of below 0.1%. A total of 65 porcine and bovine tissue samples were prepared for measurement, comprising five samples each of 13 tissue types representing about 80% of the total body mass (three different muscle and fatty tissues, liver, kidney, brain, heart, blood, lung and bone). Using a standard stoichiometric calibration for single-energy CT (SECT) as well as a state-of-the-art dual-energy CT (DECT) approach, SPR was predicted for all tissues and then compared to the measured reference. With the SECT approach, the SPRs of all tissues were predicted with a mean error of (-0.84 ± 0.12)% and a mean absolute error of (1.27 ± 0.12)%. In contrast, the DECT-based SPR predictions were overall consistent with the measured reference with a mean error of (-0.02 ± 0.15)% and a mean absolute error of (0.10 ± 0.15)%. Thus, in this study, the potential of DECT to decrease range uncertainty could be confirmed in biological tissue.

Evaluation of Additional Track Parameters from Fluorescent Nuclear Track Detectors to Determine the LET of Individual Ions.

The measurement of single-track intensity in fluorescence nuclear track detectors can yield relative linear energy transfer (LET)-spectra with small line-width. The absolute determination of LET is, however, currently hampered by the inter-detector variability of crystal coloration and hence detector sensitivity. We therefore investigated the LET response of three additional quantities (average width and the variation of intensity and width along single tracks) using detectors irradiated with mono-energetic ion beams with LETs from 1.5 to 150 keV/µm in alumina. All quantities showed in fact smaller inter-detector variability, but at the same time larger line-width and limited dynamic range as the average intensity along a track. The additional quantities might therefore serve as a helpful complement, but not as a replacement for the current approach.

Evaluation of Stopping-Power Prediction by Dual- and Single-Energy Computed Tomography in an Anthropomorphic Ground-Truth Phantom.

PURPOSE: To determine the accuracy of particle range prediction for proton and heavier ion radiation therapy based on dual-energy computed tomography (DECT) in a realistic inhomogeneous geometry and to compare it with the state-of-the-art clinical approach. METHODS AND MATERIALS: A 3-dimensional ground-truth map of stopping-power ratios (SPRs) was created for an anthropomorphic head phantom by assigning measured SPR values to segmented structures in a high-resolution CT scan. This reference map was validated independently comparing proton transmission measurements with Monte Carlo transport simulations. Two DECT-based methods for direct SPR prediction via the Bethe formula (DirectSPR) and 2 established approaches based on Hounsfield look-up tables (HLUTs) were chosen for evaluation. The SPR predictions from the 4 investigated methods were compared with the reference, using material-specific voxel statistics and 2-dimensional gamma analysis. Furthermore, range deviations were analyzed in an exemplary proton treatment plan. RESULTS: The established reference SPR map was successfully validated for the discrimination of SPR and range differences well below 0.3% and 1 mm, respectively, even in complex inhomogeneous settings. For the phantom materials of larger volume (mainly brain, soft tissue), the investigated methods were overall able to predict SPR within 1% median deviation. The DirectSPR methods generally performed better than the HLUT approaches. For smaller phantom parts (such as cortical bone, air cavities), all methods were affected by image smoothing, leading to considerable SPR under- or overestimation. This effect was superimposed on the general SPR prediction accuracy in the exemplary treatment plan. CONCLUSIONS: DirectSPR predictions proved to be more robust, with high accuracy in particular for larger volumes. In contrast, HLUT approaches exhibited a fortuitous component. The evaluation of accuracy in a realistic phantom with validated ground-truth SPR represents a crucial step toward possible clinical application of DECT-based SPR prediction methods.

Dual-energy CT based proton range prediction in head and pelvic tumor patients.

BACKGROUND AND PURPOSE: To reduce range uncertainty in particle therapy, an accurate computation of stopping-power ratios (SPRs) based on computed tomography (CT) is crucial. Here, we assess range differences between the state-of-the-art CT-number-to-SPR conversion using a generic Hounsfield look-up table (HLUT) and a direct patient-specific SPR prediction (RhoSigma) based on dual-energy CT (DECT) in 100 proton treatment fields. MATERIAL AND METHODS: For 25 head-tumor and 25 prostate-cancer patients, the clinically applied treatment plan, optimized using a HLUT, was recalculated with RhoSigma as CT-number-to-SPR conversion. Depth-dose curves in beam direction were extracted for both dose distributions in a regular grid and range deviations were determined and correlated to SPR differences within the irradiated volume. RESULTS: Absolute (relative) mean water-equivalent range shifts of 1.1mm (1.2%) and 4.1mm (1.7%) were observed in the head-tumor and prostate-cancer cohort, respectively. Due to the case dependency of a generic HLUT, range deviations within treatment fields strongly depend on the tissues traversed leading to a larger variation within one patient than between patients. CONCLUSIONS: The magnitude of patient-specific range deviations between HLUT and the more accurate DECT-based SPR prediction is clinically relevant. A clinical application of the latter seems feasible as demonstrated in this study using medically approved systems from CT acquisition to treatment planning.