Monte Carlo simulation for proton dosimetry in magnetic fields: Fano test and magnetic field correction factorskBfor Farmer-type ionization chambers.

Objective. In this contribution we present a special Fano test for charged particles in presence of magnetic fields in the MC code TOol for PArticle Simulation (TOPAS), as well as the determination of magnetic field correction factorskBfor Farmer-type ionization chambers using proton beams.Approach. Customized C++ extensions for TOPAS were implemented to model the special Fano tests in presence of magnetic fields for electrons and protons. The Geant4-specific transport parameters,DRoverRandfinalRange,were investigated to optimize passing rate and computation time. ThekBwas determined for the Farmer-type PTW 30013 ionization chamber, and 5 custom built ionization chambers with same geometry but varying inner radius, testing magnetic flux density ranging from 0 to 1.0 T and two proton beam energies of 157.43 and 221.05 MeV.Main results. Using the investigated parameters, TOPAS passed the Fano test within 0.39 ± 0.15% and 0.82 ± 0.42%, respectively for electrons and protons. The chamber response (kB,M,Q) gives a maximum at different magnetic flux densities depending of the chamber size, 1.0043 at 1.0 T for the smallest chamber and 1.0051 at 0.2 T for the largest chamber. The local dose differencecBremained ≤ 0.1% for both tested energies. The magnetic field correction factorkB, for the chamber PTW 30013, varied from 0.9946 to 1.0036 for both tested energies.Significance. The developed extension for the special Fano test in TOPAS MC code with the adjusted transport parameters, can accurately transport electron and proton particles in magnetic field. This makes TOPAS a valuable tool for the determination ofkB. The ionization chambers we tested showed thatkBremains small (≤0.72%). To the best of our knowledge, this is the first calculations ofkBfor proton beams. This work represents a significant step forward in the development of MRgPT and protocols for proton dosimetry in presence of magnetic field.

End-to-end test for fractionated online adaptive MR-guided radiotherapy using a deformable anthropomorphic pelvis phantom.

Objective.In MR-guided radiotherapy (MRgRT) for prostate cancer treatments inter-fractional anatomy changes such as bladder and rectum fillings may be corrected by an online adaption of the treatment plan. To clinically implement such complex treatment procedures, however, specific end-to-end tests are required that are able to validate the overall accuracy of all treatment steps from pre-treatment imaging to dose delivery.Approach.In this study, an end-to-end test of a fractionated and online adapted MRgRT prostate irradiation was performed using the so-called ADAM-PETer phantom. The phantom was adapted to perform 3D polymer gel (PG) dosimetry in the prostate and rectum. Furthermore, thermoluminescence detectors (TLDs) were placed at the center and on the surface of the prostate for additional dose measurements as well as for an external dose renormalization of the PG. For the end-to-end test, a total of five online adapted irradiations were applied in sequence with different bladder and rectum fillings, respectively.Main results.A good agreement of measured and planned dose was found represented by highγ-index passing rates (3%/3mmcriterion) of the PG evaluation of98.9%in the prostate and93.7%in the rectum. TLDs used for PG renormalization at the center of the prostate showed a deviation of-2.3%.Significance.The presented end-to-end test, which allows for 3D dose verification in the prostate and rectum, demonstrates the feasibility and accuracy of fractionated and online-adapted prostate irradiations in presence of inter-fractional anatomy changes. Such tests are of high clinical importance for the commissioning of new image-guided treatment procedures such as online adaptive MRgRT.

PAGAT gel dosimetry for everyone: gel production, measurement and evaluation.

Polymer gel (PG) dosimetry is a valuable tool to measure complex dose distributions in 3D with a high spatial resolution. However, due to complex protocols that need to be followed for in-house produced PGs and the high costs of commercially available gels, PG gels are only rarely applied in quality assurance procedures worldwide. In this work, we provide an introduction to perform highly standardized dosimetric PG experiments using PAGAT (PolyAcrylamide Gelatine gel fabricated at ATmospheric conditions) dosimetry gel. PAGAT gel can be produced at atmospheric conditions, at low costs and is evaluated using magnetic resonance imaging (MRI). The conduction of PG experiments is described in great detail including the gel production, treatment planning, irradiation, MRI evaluation and post-processing procedure. Furthermore, a plugin in an open source image processing tool for post-processing is provided free of charge that allows a standardized and reproducible analysis of PG experiments.

Development of phantom materials with independently adjustable CT- and MR-contrast at 0.35, 1.5 and 3 T.

Quality assurance in magnetic resonance (MR)-guided radiotherapy lacks anthropomorphic phantoms that represent tissue-equivalent imaging contrast in both computed tomography (CT) and MR imaging. In this study, we developed phantom materials with individually adjustable CT value as well as [Formula: see text]- and [Formula: see text]-relaxation times in MR imaging at three different magnetic field strengths. Additionally, their experimental stopping power ratio (SPR) for carbon ions was compared with predictions based on single- and dual-energy CT. Ni-DTPA doped agarose gels were used for individual adjustment of [Formula: see text] and [Formula: see text] at [Formula: see text] and 3.0 T. The CT value was varied by adding potassium chloride (KCl). By multiple linear regression, equations for the determination of agarose, Ni-DTPA and KCl concentrations for given [Formula: see text] [Formula: see text] and CT values were derived and employed to produce nine specific soft tissue samples. Experimental [Formula: see text] [Formula: see text] and CT values of these soft tissue samples were compared with predictions and additionally, carbon ion SPR obtained by range measurements were compared with predictions based on single- and dual-energy CT. The measured CT value, [Formula: see text] and [Formula: see text] of the produced soft tissue samples agreed very well with predictions based on the derived equations with mean deviations of less than [Formula: see text] While single-energy CT overestimates the measured SPR of the soft tissue samples, the dual-energy CT-based predictions showed a mean SPR deviation of only [Formula: see text] To conclude, anthropomorphic phantom materials with independently adjustable CT values as well as [Formula: see text] and [Formula: see text] relaxation times at three different magnetic field strengths were developed. The derived equations describe the material specific relaxation times and the CT value in dependence on agarose, Ni-DTPA and KCl concentrations as well as the chemical composition of the materials based on given [Formula: see text] and CT value. Dual-energy CT allows accurate prediction of the carbon ion range in these materials.

On the feasibility of absolute 3D dosimetry using LiF thermoluminescence detectors and polymer gels on a 0.35T MR-LINAC.

BACKGROUND AND PURPOSE: As shown in our previous study, highly accurate absolute dosimetry in 3D is feasible by combining polymer gels (PG) with thermoluminescence dosimetry (TLD). In this setup, the thermoluminescence (TL)-based point dose information is used to renormalize the PG. This new PG-TLD reference system is now extended to measurements in magnetic fields. MATERIALS AND METHODS: Experiments were carried out on a conventional 6 MV linear accelerator (LINAC) and a 6 MV 0.35 T magnetic resonance (MR)-LINAC. Signal stability of TLD600 and TLD700 was examined without and with magnetic field. Afterwards, the combination of PAGAT PG and TL detectors was employed within a cylindrical phantom in presence of the magnetic field. Two scenarios were tested: (I) an air-filled phantom and (II) a water-filled phantom. For each scenario, two plans were irradiated: (a) opposed beams with a field size of 10 × 10 cm2 and (b) a 3D conformal plan assuring homogeneous target coverage using three equally distributed coplanar beams. RESULTS: Mean relative uncertainty of TL calibration reproducibility for TLD600/TLD700 was 0.49%/0.85% at the MR-LINAC and 0.48%/0.83% for the conventional LINAC. Individual TL calibration coefficients of TLD600 and TLD700 behaved differently in the presence of the magnetic field. An average difference of (3.29 ± 0.89)% occurred for all TLD600, whereas the result for TLD700 is not quite as clear with (1.09 ± 0.89)% after excluding some outliers. Using the TL dose information for PG renormalization, high 3D gamma passing rates were achieved using the 3%/2 mm criteria: 91.0% (Ia), 92.6% (Ib), 94.3% (IIa), 97.4% (IIb). CONCLUSION: This study shows that TL signal reproducibility is not affected by a low magnetic field. Nevertheless, absolute calibration coefficients of the individual detectors indicate a dependency on the magnetic field. Hence, a calibration at the appropriate LINAC type is recommended. Furthermore, the previously established renormalization method for PG was applied to measurements at a MR-LINAC and was verified as suitable for evaluations of homogeneous dose distribution in the target volume.

Impact of Gaussian uncertainty assumptions on probabilistic optimization in particle therapy.

Range and setup uncertainties in charged particle therapy may induce a discrepancy between the planned and the delivered dose. Countermeasures based on probabilistic (stochastic) optimization usually assume a Gaussian probability density to model the underlying range and setup error. While this standard assumption is generally taken for granted, this study explicitly investigates the dosimetric consequences if the actual range and setup errors obey a different probability density function (PDF) over the course of treatment to the one used during the probabilistic treatment plan optimization. Discrete random sampling was performed for conventionally and probabilistically optimized proton and carbon ion treatment plans utilizing various PDFs that modeled the setup and range error. This method allowed us to assess the treatment plan robustness against different PDFs of conventional and probabilistic plans, which both explicitly assume Gaussian uncertainties. The induced uncertainty in dose was quantified by estimating the expectation value and standard deviation of the RBE-weighted dose for each PDF on the basis of 2500-5000 random dose samples. Probabilistic dose metrics and standard deviation volume histograms were computed to quantify treatment plan robustness of both optimization approaches. It was shown that the classical planning target volume margin extension concept did not compensate the influence of range and setup errors and consequently resulted in a non-negligible average standard deviation in dose of 7.3% throughout the clinical target volume (CTV). In contrast, probabilistic optimization on normally distributed errors yielded treatment plans that not only entailed a lower standard deviation against normally distributed errors accounted for during optimization, but also lower standard deviations for other symmetric PDFs. It was shown that the impact of an incorrect probability distribution assumption is of lower importance after probabilistic optimization as the average uncertainty in the CTV drops to 3.9%. Probabilistic optimization is an effective tool to create robust particle treatment plans. Normally distributed range and setup error assumptions for probabilistic optimization are a reasonable first approximation and yield treatment plans that are also robust against other PDFs.

Feasibility of markerless fluoroscopic real-time tumor detection for adaptive radiotherapy: development and end-to-end testing.

Respiratory-gated radiotherapy treatments of lung tumors reduce the irradiated normal tissue volume and potentially lower the risk of side effects. However, in clinical routine, the gating signal is usually derived from external markers or other surrogate signals and may not always correlate well with the actual tumor position. This study uses the kV-imaging system of a LINAC in combination with a multiple template matching algorithm for markerless real-time detection of the tumor position in a dynamic anthropomorphic porcine lung phantom. The tumor was realized by a small container filled with polymer dosimetry gel, the so-called gel tumor. A full end-to-end test for a gated treatment was performed and the geometric and dosimetric accuracy was validated. The accuracy of the tumor detection algorithm in SI- direction was found to be [Formula: see text] mm and the gel tumor was automatically detected in 98 out of 100 images. The measured 3D dose distribution showed a uniform coverage of the gel tumor and comparison with the treatment plan revealed a high 3D [Formula: see text]-passing rate of [Formula: see text] ([Formula: see text]). The simulated treatment confirmed the employed margin sizes for residual motion within the gating window and serves as an end-to-end test for a gated treatment based on a markerless fluoroscopic real-time tumor detection.

End-to-end test of an online adaptive treatment procedure in MR-guided radiotherapy using a phantom with anthropomorphic structures.

Online adaptive treatment procedures in magnetic resonance (MR)-guided radiotherapy (MRgRT) allow compensating for inter-fractional anatomical variations in the patient. Clinical implementation of these procedures, however, requires specific end-to-end tests to validate the treatment chain including imaging, treatment planning, positioning, treatment plan adaption and accurate dose delivery. For this purpose, a new phantom with reproducibly adjustable anthropomorphic structures has been developed. These structures can be filled either with contrast materials providing anthropomorphic image contrast in MR and CT or with polymer dosimetry gel (PG) allowing for 3D dose measurements. To test an adaptive workflow at a 0.35 T MR-Linac, the phantom was employed in two settings simulating inter-fractional anatomical variations within the patient. The settings included two PG-filled structures representing a tumour and an adjacent organ at risk (OAR) as well as five additional structures. After generating a treatment plan, three irradiation experiments were performed: (i) delivering the treatment plan to the phantom in reference setting, (ii) delivering the treatment plan after changing the phantom to a displaced setting without adaption, and (iii) adapting the treatment plan online to the new setting and delivering it to the phantom. PG measurements revealed a homogeneous tumour coverage and OAR sparing for experiment (i) and a significant under-dosage in the PTV (down to 45% of the prescribed dose) and over-dosage in the OAR (up to 180% relative to the planned dose) in experiment (ii). In experiment (iii), a uniform dose in the PTV and a significantly reduced dose in the OAR was obtained, well-comparable to that of experiment (i) where no adaption of the treatment plan was necessary. PG measurements were well comparable with the corresponding treatment plan in all irradiation experiments. The developed phantom can be used to perform end-to-end tests of online adaptive treatment procedures at MR-Linac devices before introducing them to patients.

Measurement of isocenter alignment accuracy and image distortion of an 0.35 T MR-Linac system.

For hybrid devices combining magnetic resonance (MR) imaging and a linac for radiation treatment, the isocenter accuracy as well as image distortions have to be checked. This study presents a new phantom to investigate MR-Linacs in a single measurement in terms of (i) isocentricity of the irradiation and (ii) alignment of the irradiation and imaging isocenter relative to each other using polymer dosimetry gel as well as (iii) 3-dimensional (3D) geometric MR image distortions. The evaluation of the irradiated gel was performed immediately after irradiation with the imaging component of the 0.35 T MR-Linac using a T2-weighted turbo spin-echo sequence. Eight plastic grid sheets within the phantom allow for measurement of geometric distortions in 3D by comparing the positions of the grid intersections (control points) within the MR-image with their nominal position obtained from a CT-scan. The distance of irradiation and imaging isocenter in 3D was found to be (0.8 ± 0.9) mm for measurements with 32 image acquisitions. The mean distortion over the whole phantom was (0.60 ± 0.28) mm and 99.8% of the evaluated control points had distortions below 1.5 mm. These geometrical uncertainties have to be considered by additional safety margins.

Compatibility of 3D printing materials and printing techniques with PAGAT gel dosimetry.

Polymer gel (PG) dosimetry enables three dimensional (3D) measurement of complex dose distributions. However, PGs are strongly reactive with oxygen and other contaminations, limiting their applicability by the need to use specific container materials. We investigate different 3D printing materials and printing techniques for their compatibility with PG. Suitable 3D printing materials may provide the possibility to perform PG dosimetry in complex-shaped phantoms. 3D printed and PG-filled test vials were irradiated homogenously. The signal response was evaluated with respect to homogeneity and compared to the signal in already validated reference vials. In addition, for the printing material VeroClear™ (StrataSys, Eden Prairie, USA) different methods to remove support material, which was required during the printing process, were investigated. We found that the support material should be used only on the outer side of the container wall with no direct contact to the PG. With the VeroClear™ material a homogenous signal response was achieved with a mean deviation of [Formula: see text] relative to the reference vials. In addition, the homogeneous irradiation of an irregularly-shaped gel container designed with the same printing material and technique also lead to a homogenous PG response. Furthermore, a small field irradiation of an additional test-vial showed an accurate representation of steep dose gradients with a deviation of the maximum position of [Formula: see text] relative to the reference vial.

Absolute dosimetry with polymer gels-a TLD reference system.

BACKGROUND AND PURPOSE: Absolute dosimetry in 3D with polymer gels (PG) is generally complicated and usually requires a second independent measurement with conventional detectors. This is why, PG are often used only for relative dosimetry. To overcome this drawback, we combine PG with a 1D thermoluminescence (TL) detector within the same measurement. The TL detector information is then used as additional information for calibration of the gel. MATERIALS AND METHODS: The PAGAT dosimetry gel was used in combination with TLD600 (LiF:Mg,Ti). TL detectors were attached on the surface of the PG container placed inside a cylindrical phantom. To test the usability of this setup, two irradiation geometries were carried out: (a) homogeneous target coverage and (b) small-field irradiation. PG was evaluated with magnetic resonance imaging (MRI) and the TL detectors with a Harshaw 5500 hot gas reader. RESULTS: PG dosimetry alone showed deviations of up to 4% as compared to calculations. Including additionally the dose information of the TL detectors for PG calibration, this deviation was decreased to less than 1% for both irradiation geometries. This is also reflected by the very high [Formula: see text]-passing rates of > 96% (3%/3 mm) and >93% (2%/2 mm), respectively. CONCLUSION: This study presents a novel method combining 3D PG and TL dose measurements for the purpose of absolute 3D dose measurements that can also be applied in complex anthropomorphic phantoms using only a single measurement. The method was validated for two different irradiation geometries including a homogeneous large field as well as a small field irradiation with sharp dose gradients.

Feasibility of polymer gel-based measurements of radiation isocenter accuracy in magnetic fields.

For conventional irradiation devices, the radiation isocenter accuracy is determined by star shot measurements on films. In magnetic resonance (MR)-guided radiotherapy devices, the results of this test may be altered by the magnetic field and the need to align the radiation and imaging isocenter may require a modification of measurement procedures. Polymer dosimetry gels (PG) may offer a way to perform both, the radiation and imaging isocenter test, however, first it has to be shown that PG reveal results comparable to the conventionally applied films. Therefore, star shot measurements were performed at a linear accelerator using PG as well as radiochromic films. PG were evaluated using MR imaging and the isocircle radius and the distance between the isocircle center and the room isocenter were determined. Two different types of experiments were performed: i) a standard star-shot isocenter test and (ii) a star shot, where the detectors were placed between the pole shoes of an experimental electro magnet operated either at 0 T or 1 T. For the standard star shot, PG evaluation was independent of the time delay after irradiation (1 h, 24 h, 48 h and 216 h) and the results were comparable to those of film measurements. Within the electro magnet, the isocircle radius increased from 0.39 ± 0.01 mm to 1.37 ± 0.01 mm for the film and from 0.44 ± 0.02 mm to 0.97 ± 0.02 mm for the PG-measurements, respectively. The isocenter distance was essentially dependent on the alignment of the magnet to the isocenter and was between 0.12 ± 0.02 mm and 0.82 ± 0.02 mm. The study demonstrates that evaluation of the PG directly after irradiation is feasible, if only geometrical parameters are of interest. This allows using PG for star shot measurements to evaluate the radiation isocenter accuracy with comparable accuracy as with radiochromic films.

Radiation dosimetry in magnetic fields with Farmer-type ionization chambers: determination of magnetic field correction factors for different magnetic field strengths and field orientations.

The aim of this work was to determine magnetic field correction factors that are needed for dosimetry in hybrid devices for MR-guided radiotherapy for Farmer-type ionization chambers for different magnetic field strengths and field orientations. The response of six custom-built Farmer-type chambers irradiated at a 6 MV linac was measured in a water tank positioned in a magnet with magnetic field strengths between 0.0 T and 1.1 T. Chamber axis, beam and magnetic field were perpendicular to each other and both magnetic field directions were investigated. EGSnrc Monte Carlo simulations were compared to the measurements and simulations with different field orientations were performed. For all geometries, magnetic field correction factors, [Formula: see text], and perturbation factors were calculated. A maximum increase of 8.8% in chamber response was measured for the magnetic field perpendicular to chamber and beam axis. The measured chamber response could be reproduced by adjusting the dead volume layer near the chamber stem in the Monte Carlo simulations. For the magnetic field parallel to the chamber axis or parallel to the beam, the simulated response increased by 1.1% at maximum for field strengths up to 1.1 T. A complex dependence of the response was found on chamber radius, magnetic field strength and orientation of beam, chamber axis and magnetic field direction. Especially for magnetic fields perpendicular to beam and chamber axis, the exact sensitive volume has to be considered in the simulations. To minimize magnetic field correction factors and the influence of dead volumes on the response of Farmer chambers, a measurement set-up with the magnetic field parallel to the chamber axis or parallel to the beam is recommended for dosimetry.

3D dosimetric validation of motion compensation concepts in radiotherapy using an anthropomorphic dynamic lung phantom.

In this study, we developed a new setup for the validation of clinical workflows in adaptive radiation therapy, which combines a dynamic ex vivo porcine lung phantom and three-dimensional (3D) polymer gel dosimetry. The phantom consists of an artificial PMMA-thorax and contains a post mortem explanted porcine lung to which arbitrary breathing patterns can be applied. A lung tumor was simulated using the PAGAT (polyacrylamide gelatin gel fabricated at atmospheric conditions) dosimetry gel, which was evaluated in three dimensions by magnetic resonance imaging (MRI). To avoid bias by reaction with oxygen and other materials, the gel was collocated inside a BAREX™ container. For calibration purposes, the same containers with eight gel samples were irradiated with doses from 0 to 7 Gy. To test the technical feasibility of the system, a small spherical dose distribution located completely within the gel volume was planned. Dose delivery was performed under static and dynamic conditions of the phantom with and without motion compensation by beam gating. To verify clinical target definition and motion compensation concepts, the entire gel volume was homogeneously irradiated applying adequate margins in case of the static phantom and an additional internal target volume in case of dynamically operated phantom without and with gated beam delivery. MR-evaluation of the gel samples and comparison of the resulting 3D dose distribution with the planned dose distribution revealed a good agreement for the static phantom. In case of the dynamically operated phantom without motion compensation, agreement was very poor while additional application of motion compensation techniques restored the good agreement between measured and planned dose. From these experiments it was concluded that the set up with the dynamic and anthropomorphic lung phantom together with 3D-gel dosimetry provides a valuable and versatile tool for geometrical and dosimetrical validation of motion compensated treatment concepts in adaptive radiotherapy.

A motorized solid-state phantom for patient-specific dose verification in ion beam radiotherapy.

For regular quality assurance and patient-specific dosimetric verification under non-horizontal gantry angles in ion beam radiotherapy, we developed and commissioned a motorized solid state phantom. The phantom is set up under the selected gantry angle and moves an array of 24 ionization chambers to the measurement position by means of three eccentrically-mounted cylinders. Hence, the phantom allows 3D dosimetry at oblique gantry angles. To achieve the high standards in dosimetry, the mechanical and dosimetric accuracy of the phantom was investigated and corrections for residual uncertainties were derived. Furthermore, the exact geometry as well as a coordinate transformation from cylindrical into Cartesian coordinates was determined. The developed phantom proved to be suitable for quality assurance and 3D-dose verifications for proton- and carbon ion treatment plans at oblique gantry angles. Comparing dose measurements with the new phantom under oblique gantry angles with those in a water phantom and horizontal beams, the dose deviations averaged over the 24 ionization chambers were within 1.5%. Integrating the phantom into the HIT treatment plan verification environment, allows the use of established workflow for verification measurements. Application of the phantom increases the safety of patient plan application at gantry beam lines.

A voxel-based multiscale model to simulate the radiation response of hypoxic tumors.

PURPOSE: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. METHODS: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. RESULTS: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was found to be significantly more important for reoxygenation than angiogenesis or decreased oxygen consumption due to an increased fraction of dead cells. In the studied HNSSC-case, the TCD50 values (dose at 50% TCP) decreased from 71.0 Gy under hypoxic to 53.6 Gy under the oxic condition. CONCLUSIONS: The results obtained with the developed multiscale model are in accordance with expectations based on radiobiological principles and clinical experience. As the model is voxel-based, radiological imaging methods may help to provide the required 3D-characterization of the tumor prior to irradiation. For clinical application, the model has to be further validated with experimental and clinical data. If this is achieved, the model may be used to optimize fractionation schedules and dose distributions for the treatment of hypoxic tumors.

Estimation of the uncertainty of elastic image registration with the demons algorithm.

The accuracy of elastic image registration is limited. We propose an approach to detect voxels where registration based on the demons algorithm is likely to perform inaccurately, compared to other locations of the same image. The approach is based on the assumption that the local reproducibility of the registration can be regarded as a measure of uncertainty of the image registration. The reproducibility is determined as the standard deviation of the displacement vector components obtained from multiple registrations. These registrations differ in predefined initial deformations. The proposed approach was tested with artificially deformed lung images, where the ground truth on the deformation is known. In voxels where the result of the registration was less reproducible, the registration turned out to have larger average registration errors as compared to locations of the same image, where the registration was more reproducible. The proposed method can show a clinician in which area of the image the elastic registration with the demons algorithm cannot be expected to be accurate.

Impact of enhancements in the local effect model (LEM) on the predicted RBE-weighted target dose distribution in carbon ion therapy.

Biological optimization for treatment planning in carbon ion therapy is currently based on the first version of the local effect model (LEM I). Further developments implemented in the latest version (LEM IV) allowed to predict more accurately the Relative Biological Effectiveness (RBE) in-vitro. The main goal of this study is to compare the LEM IV against LEM I under treatment-like conditions for idealized target geometries. Therefore, physical dose distributions resulting from the biological optimization with LEM I were used to recalculate the RBE-weighted dose distribution based on LEM IV. Input parameters representing the clinical endpoints late toxicity in the central nervous system and the tumor control for chordoma were chosen to investigate the impact of changes on the predicted isoeffective dose levels. The recalculated RBE-weighted dose distributions show an increase within the target region, and the mean RBE-weighted dose values are dependent on the geometry and decrease with increasing target dimension. The differences between predictions of LEM IV and LEM I are less than 10% for typical tumor volumes treated in the pilot project at GSI. Median RBE-weighted doses predicted by LEM IV in the target region are consistent with clinically observed dose-response behavior as demonstrated by comparison to the 5-year local control curve for skull base chordoma.

Experimental determination of the effective point of measurement and the displacement correction factor for cylindrical ionization chambers in a 6 MV photon beam.

The displacement effect of cylindrical ionization chambers is taken into account either by an effective point of measurement (EPOM) or, alternatively, by using a displacement correction factor. The dependence of these effects on water was examined as a function of the cavity radius for (60)Co gamma radiation in a previous paper. This paper describes results for high-energy photon beams using the same measurement technique. Additionally, the displacement correction factor was directly measured. Absorbed doses measured under reference conditions following the international protocol IAEA TRS-398 and the German protocol DIN 6800-2 agreed well between the chambers with different cavity radii within a standard uncertainty of 0.2%. However, there was a constant difference of 0.2% between both protocols. Similar to our observations made in (60)Co, absorbed doses measured with the different chambers at depths beyond the maximum showed deviations of up to 0.6% and 0.5% for IAEA TRS-398 and DIN 6800-2, respectively, and deviations of more than 1% were found for both protocols in the build-up and maximum region. We therefore propose modified formulas for the determination of the EPOM and the displacement correction factor.

Experimental determination of the effective point of measurement for cylindrical ionization chambers in 60Co gamma radiation.

The displacement effect of cylindrical ionization chambers is taken into account either by an effective point of measurement (EPOM) or, alternatively, by using a displacement perturbation factor. The dependence of these effects in water was examined as a function of the cavity radius using cylindrical chambers with different radii and a plane-parallel chamber, whose EPOM is well known. Depth-dose curves were measured in terms of absolute absorbed dose in water and evaluated according to the international protocol IAEA TRS-398 as well as the German protocol DIN 6800-2. As expected, evaluation of absorbed dose under reference conditions following both protocols agreed well within a standard uncertainty of 0.1%. However, values of absorbed dose at depths beyond the dose maximum showed deviations up to 0.3% and 0.5% for IAEA TRS-398 and DIN 6800-2, respectively. Values in the build-up and maximum region did not agree very well. Deviations of more than 1% were found for both protocols. It was concluded that the corrections recommended in both protocols are not fully appropriate. A procedure is suggested to measure the absorbed depth-dose distribution including the build-up region with an improved accuracy by means of cylindrical chambers.