Search

Brachytherapy has an excellent clinical outcome for different treatment sites. However, in vivo treatment verification is not performed in the majority of hospitals due to the lack of proper monitoring systems. This study investigates the use of an imaging panel (IP) and the photons emitted by a high dose rate (HDR) Ir-192 source to track source motion and obtain some information related to the patient anatomy. The feasibility of this approach was studied by monitoring the treatment delivery to a 3D printed phantom that mimicks a prostate patient. A 3D printed phantom was designed with a template for needle insertion, a cavity ('rectum') to insert an ultrasound probe, and lateral cavities used to place tissue-equivalent materials. CT images were acquired to create HDR Ir-192 treatment plans with a range of dwell times, interdwell distances and needle arrangements. Treatment delivery was verified with an IP placed at several positions around the phantom using radiopaque markers on the outer surface to register acquired IP images with the planning CT. All dwell positions were identified using acquisition times = 9 fps). Interdwell distances and dwell positions (in relation to the IP) were verified with accuracy better than 0.1 cm. Radiopaque markers were visible in the acquired images and could be used for registration with CT images. Uncertainties for image registration (IP and planning CT) between 0.1 and 0.4 cm. The IP is sensitive to tissue-mimicking insert composition and showed phantom boundaries that could be used to improve treatment verification. The IP provided sufficient time and spatial resolution for real-time source tracking and allows for the registration of the planning CT and IP images. The results obtained in this study indicate that several treatment errors could be detected including swapped catheters, incorrect dwell times and dwell positions. This project was partially supported by Varian Medical Systems. We thank Stavroula Giannuli and Rebecca Park from Varian for commenting on the paper. G P Fonseca and T van Wagenberg were supported by KWF (Grant 12780-Bas Mulder award). We thank Vera Schroen, Janneke Cruts and Esther Visser for their contribution to this project. Fonseca, GP (corresponding author), Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Med Ctr, Doctor Tanslaan 12, NL-6229 ET Maastricht, Netherlands. gabriel.paivafonseca@maastro.nl

X-ray tubes for medical applications typically generate x-rays by accelerating electrons, emitted from a cathode, with an interelectrode electric field, towards an anode target. X-rays are not emitted from one point, but from an irregularly shaped area on the anode, the focal spot. Focal spot intensity distributions and off-focal radiation negatively affect the imaging spatial resolution and broadens the beam penumbra. In this study, a Monte Carlo simulation model of an x-ray tube was developed to evaluate the spectral and spatial characteristics of off-focal radiation for multiple photon energies. Slit camera measurements were used to determine the horizontal and vertical intensity profiles of the small and the large focal spot of a diagnostic x-ray tube. First, electron beamlet weighting factors were obtained via an iterative optimization method to represent both focal spot sizes. These weighting factors were then used to extract off-focal spot radiation characteristics for the small and large focal spot sizes at 80, 100, and 120 kV. Finally, 120 kV simulations of a steel sphere (d = 4 mm) were performed to investigate image blurring with a point source, the small focal spot, and the large focal spot. The magnitude of off-focal radiation strongly depends on the anode size and the electric field coverage, and only minimally on the tube potential and the primary focal spot size. In conclusion, an x-ray tube Monte Carlo simulation model was developed to simulate focal spot intensity distributions and to evaluate off-focal radiation characteristics at several energies. This model can be further employed to investigate focal spot correction methods and to improve cone-beam CT image quality.

A novel system was developed to improve commissioning and quality assurance of brachytherapy applicators used in high dose rate (HDR). It employs an imaging panel to create reference images and to measure dwell times and dwell positions. As an example: two ring applicators of the same model were evaluated. An applicator was placed on the surface of an imaging panel and a HDR 192Ir source was positioned in an imaging channel above the panel to generate an image of the applicator, using the gamma photons of the brachytherapy source. The applicator projection image was overlaid with the images acquired by capturing the gamma photons emitted by the source dwelling inside the applicator. We verified 0.1, 0.2, 0.5 and 1.0 cm interdwell distances for different offsets, applicator inclinations and transfer tube curvatures. The data analysis was performed using in-house developed software capable of processing the data in real time, defining catheters and creating movies recording the irradiation procedure. One applicator showed up to 0.3 cm difference from the expected position for a specific dwell position. The problem appeared intermittently. The standard deviations of the remaining dwell positions (40 measurements) were less than 0.05 cm. The second ring applicator had a similar reproducibility with absolute coordinate differences from expected values ranging from -0.10 up to 0.18 cm. The curvature of the transfer tube can lead to differences larger than 0.1 cm whilst the inclination of the applicator showed a negligible effect. The proposed method allows the verification of all steps of the irradiation, providing accurate information about dwell positions and dwell times. It allows the verification of small interdwell positions (⩽0.1 cm) and reduces measurement time. In addition, no additional radiation source is necessary since the HDR 192Ir source is used to generate an image of the applicator.

Purpose: It is desirable that dosimetric deviations during radiation treatments are detected. Integrated transit planar dosimetry is commonly used to evaluate external beam treatments such as volumetric-modulated arc therapy. This work focuses on patient geometry changes which result in differences between the planned and the delivered radiation dose. Integrated transit planar dosimetry will average out some deviations. Novel time-resolved transit planar dosimetry compares the delivered dose of volumetric-modulated arc therapy to the planned dose at various time points. Four patient cases are shown where time-resolved transit planar dosimetry detects patient geometry changes during treatment. Methods: A control point to control point comparison between the planned dose and the treatment dose of volumetric-modulated arc therapy beams is calculated using the planning computed tomography and the kV cone-beam computed tomography of the day and evaluated with a time-resolved γ function. Results were computed for 4 patients treated with volumetric-modulated arc therapy, each showing an anatomical change: pleural effusion, rectal gas pockets, and tumor regression. Results: In all cases, the geometrical change was detected by time-resolved transit planar dosimetry, whereas integrated transit planar dosimetry showed minor or no indication of the dose discrepancy. Both tumor regression cases were detected earlier in the treatment with time-resolved planar dosimetry in comparison to integrated transit planar dosimetry. The pleural effusion and the gas pocket were detected exclusively with time-resolved transit planar dosimetry. Conclusions: Clinical cases were presented in this proof-of-principle study in which integrated transit planar dosimetry did not detect dosimetrically relevant deviations to the same extent time-resolved transit planar dosimetry was able to. Time-resolved transit planar dosimetry also provides results that can be presented as a function of arc delivery angle allowing easier interpretation compared to integrated transit planar dosimetry.

Purpose This work aims at investigating intensity corrected cone-beam x-ray computed tomography (CBCT) images for accurate dose calculation in adaptive intensity modulated proton therapy (IMPT) for prostate and head and neck (H&N) cancer. A deformable image registration (DIR)-based method and a scatter correction approach using the image data obtained from DIR as prior are characterized and compared on the basis of the same clinical patient cohort for the first time. Methods Planning CT (pCT) and daily CBCT data (reconstructed images and measured projections) of four H&N and four prostate cancer patients have been considered in this study. A previously validated Morphons algorithm was used for DIR of the planning CT to the current CBCT image, yielding a so-called virtual CT (vCT). For the first time, this approach was translated from H&N to prostate cancer cases in the scope of proton therapy. The warped pCT images were also used as prior for scatter correction of the CBCT projections for both tumor sites. Single field uniform dose and IMPT (only for H&N cases) treatment plans have been generated with a research version of a commercial planning system. Dose calculations on vCT and scatter corrected CBCT (CBCTcor) were compared by means of the proton range and a gamma-index analysis. For the H&N cases, an additional diagnostic replanning CT (rpCT) acquired within three days of the CBCT served as additional reference. For the prostate patients, a comprehensive contour comparison of CBCT and vCT, using a trained physician's delineation, was performed. Results A high agreement of vCT and CBCTcor was found in terms of the proton range and gamma-index analysis. For all patients and indications between 95% and 100% of the proton dose profiles in beam's eye view showed a range agreement of better than 3 mm. The pass rate in a (2%,2 mm) gamma-comparison was between 96% and 100%. For H&N patients, an equivalent agreement of vCT and CBCTcor to the reference rpCT was observed. However, for the prostate cases, an insufficient accuracy of the vCT contours retrieved from DIR was found, while the CBCTcor contours showed very high agreement to the contours delineated on the raw CBCT. Conclusions For H&N patients, no considerable differences of vCT and CBCTcor were found. For prostate cases, despite the high dosimetric agreement, the DIR yields incorrect contours, probably due to the more pronounced anatomical changes in the abdomen and the reduced soft-tissue contrast in the CBCT. Using the vCT as prior, these inaccuracies can be overcome and images suitable for accurate delineation and dose calculation in CBCT-based adaptive IMPT can be retrieved from scatter correction of the CBCT projections.

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min(-1) and 12 Gy min(-1) but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates

The aim of this work is to compare time-resolved (TR) and time-integrated (TI) portal dosimetry, focussing on the role of an object's position with respect to the isocenter in volumetric modulated arc therapy (VMAT). Portal dose images (PDIs) are simulated and measured for different cases: a sphere (1), a bovine bone (2) and a patient geometry (3). For the simulated case (1) and the experimental case (2), several transformations are applied at different off-axis positions. In the patient case (3), three simple plans with different isocenters are created and pleural effusion is simulated in the patient. The PDIs before and after the sphere transformations, as well as the PDIs with and without simulated pleural effusion, are compared using a TI and TR gamma analysis. In addition, the performance of the TI and TR gamma analyses for the detection of real geometric changes in patients treated with clinical plans is investigated and a correlation analysis is performed between gamma fail rates and differences in dose volume histogram (DVH) metrics. The TI gamma analysis can show large differences in gamma fail rates for the same transformation at different off-axis positions (or for different plan isocenters). The TR gamma analysis, however, shows consistent gamma fail rates. For the detection of real geometric changes in patients treated with clinical plans, the TR gamma analysis has a higher sensitivity than the TI gamma analysis. However, the specificity for the TR gamma analysis is lower than for the TI gamma analysis. Both the TI and TR gamma fail rates show no correlation with changes in DVH metrics. This work shows that TR portal dosimetry is fundamentally superior to TI portal dosimetry, because it removes the strong dependence of the gamma fail rate on the off-axis position/plan isocenter. However, for 2D TR portal dosimetry, it is still difficult to interpret gamma fail rates in terms of changes in DVH metrics for patients treated with VMAT.

Purpose: Imaging of patient anatomy during treatment is a necessity for position verification and for adaptive radiotherapy based on daily dose recalculation. Ultrasound(US)image guided radiotherapy systems are currently available to collect USimages at the simulation stage (USsim), coregistered with the simulation computed tomography(CT), and during all treatment fractions. The authors hypothesize that a deformation field derived from US-based deformable image registration can be used to create a daily pseudo-CT (CTps) image that is more representative of the patients’ geometry during treatment than the CT acquired at simulation stage (CTsim). Methods: The three prostate patients, considered to evaluate this hypothesis, had coregistered CT and US scans on various days. In particular, two patients had two US–CT datasets each and the third one had five US–CT datasets. Deformation fields were computed between pairs of USimages of the same patient and then applied to the corresponding USsim scan to yield a new deformed CTps scan. The original treatment plans were used to recalculate dose distributions in the simulation, deformed and ground truth CT(CTgt) images to compare dice similarity coefficients, maximum absolute distance, and mean absolute distance on CT delineations and gamma index (γ) evaluations on both the Hounsfield units (HUs) and the dose. Results: In the majority, deformation did improve the results for all three evaluation methods. The change in gamma failure for dose (γDose, 3%, 3 mm) ranged from an improvement of 11.2% in the prostate volume to a deterioration of 1.3% in the prostate and bladder. The change in gamma failure for the CTimages (γCT, 50 HU, 3 mm) ranged from an improvement of 20.5% in the anus and rectum to a deterioration of 3.2% in the prostate. Conclusions: This new technique may generate CTpsimages that are more representative of the actual patient anatomy than the CTsim scan.

Objective: To analyse the effect of different image reconstruction techniques on image quality and dual energy CT (DECT) imaging metrics.Methods: A software platform for pre-clinical cone beam CT X-ray image reconstruction was built using the open-source reconstruction toolkit. Pre-processed projections were reconstructed with filtered back-projection and iterative algorithms, namely Feldkamp, Davis, and Kress (FDK), Iterative FDK, simultaneous algebraic reconstruction technique (SART), simultaneous iterative reconstruction technique and conjugate gradient. Imaging metrics were quantitatively assessed, using a quality assurance phantom, and DECT analysis was performed to determine the influence of each reconstruction technique on the relative electron density (rho(e)) and effective atomic number (Z(eff)) values.Results: Iterative reconstruction had favourable results for the DECT analysis: a significantly smaller spread for each material in the rho(e)-Z(eff) space and lower Z(eff) and rho(e) residuals (on average 24 and 25% lower, respectively). In terms of image quality assurance, the techniques FDK, Iterative FDK and SART provided acceptable results. The three reconstruction methods showed similar geometric accuracy, uniformity and CT number results. The technique SART had a contrast-to-noise ratio up to 76% higher for solid water and twice as high for Teflon, but resolution was up to 28% lower when compared to the other two techniques.Conclusions: Advanced image reconstruction can be beneficial, but the benefit is small, and calculation times may be unacceptable with current technology. The use of targeted and downscaled reconstruction grids, larger, yet practicable, pixel sizes and GPU are recommended.Advances in knowledge: An iterative CBCT reconstruction platform was build using RTK.

Objective: During the treatment planning of a preclinical small animal irradiation, which has time limitations for reasons of animal wellbeing and workflow efficiency, the time consuming organ at risk (OAR) delineation is performed manually. This work aimed to develop, demonstrate, and quantitatively evaluate an automated contouring method for six OARs in a preclinical irritation treatment workflow.Methods: Microcone beam CT images of nine healthy mice were contoured with an in-house developed multiatlas-based image segmentation (MABIS) algorithm for six OARs: kidneys, eyes, heart, and brain. The automatic contouring was compared with the manual delineation using three quantitative metrics: the Dice Similarity Coefficient (DSC), 95th percentile Hausdorff Distance, and the centre of mass displacement.Results: A good agreement between manual and automatic contouring was found for OARS with sharp organ boundaries. For the brain and the heart, the median DSC was larger than 0.94, the median 95th Hausdorff Distance smaller than 0.44 mm, and the median centre of mass displacement smaller than 0.20 mm. Lower DSC values were obtained for the other OARs, but the median DSC was still larger than 0.74 for the left eye, 0.69 for the right eye, 0.89 for the left kidney and 0.80 for the right kidney.Conclusion: The MABIS algorithm was able to delineate six OARs with a relatively high accuracy. Segmenting OARS with sharp organ boundaries performed better than low contrast OARs.Advances in knowledge: A MABIS algorithm is developed, evaluated, and demonstrated in a preclinical small animal irradiation research workflow.

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are relatively complex treatment delivery techniques and require quality assurance (QA) procedures. Pre-treatment dosimetric verification represents a fundamental QA procedure in daily clinical routine in radiation therapy. The purpose of this study is to develop an EPID-based approach to reconstruct a 3D dose distribution as imparted to a virtual cylindrical water phantom to be used for plan-specific pre-treatment dosimetric verification for IMRT and VMAT plans. For each depth, the planar 2D dose distributions acquired in air were back-projected and convolved by depth-specific scatter and attenuation kernels. The kernels were obtained by making use of scatter and attenuation models to iteratively estimate the parameters from a set of reference measurements. The derived parameters served as a look-up table for reconstruction of arbitrary measurements. The summation of the reconstructed 3D dose distributions resulted in the integrated 3D dose distribution of the treatment delivery. The accuracy of the proposed approach was validated in clinical IMRT and VMAT plans by means of gamma evaluation, comparing the reconstructed 3D dose distributions with Octavius measurement. The comparison was carried out using (3%, 3 mm) criteria scoring 99% and 96% passing rates for IMRT and VMAT, respectively. An accuracy comparable to the one of the commercial device for 3D volumetric dosimetry was demonstrated. In addition, five IMRT and five VMAT were validated against the 3D dose calculation performed by the TPS in a water phantom using the same passing rate criteria. The median passing rates within the ten treatment plans was 97.3%, whereas the lowest was 95%. Besides, the reconstructed 3D distribution is obtained without predictions relying on forward dose calculation and without external phantom or dosimetric devices. Thus, the approach provides a fully automated, fast and easy QA procedure for plan-specific pre-treatment dosimetric verification.

Background and purpose: Dedicated CT simulation models have the potential to investigate several acquisition, reconstruction, or post-processing parameters without giving any radiation dose to patients. A software program was developed for the simulation and the analysis of single-energy and dual-energy CT images. Simulation and analysis functionalities of the software are described. Materials and methods: In the software, named VOXSI (VOXelized CT SImulator), the X-ray source, user specified simulation geometry, CT setup and the detector energy response can be varied. CT image reconstructions can be performed with an implementation of the ASTRA toolbox. In the DECT post processing toolkit, GUI tools are provided to calculate effective atomic number, relative electron density, pseudo-monoenergetic images, and material map images. Quantitative CT number validation, based on a RMI 467 tissue characterization phantom model, was performed between experimental and simulated CT scans at three different X-ray tube potentials (80, 120, and 140 kVp) with a third generation CT scanner. Results: Overall, a good agreement was found for the mean CT numbers of the RMI 467 inserts. For all energies, the maximum difference in CT numbers between experimental and simulated data was below 17 HU for the soft tissues and below 48 HU for the osseous tissues. Conclusion: The software’s simulation algorithm showed a good agreement between the CT measurements and CT simulations of the RMI 467 phantom at different energies. The capabilities of the software are demonstrated by an elaborated dual-energy CT research example. Keywords: Single-energy CT, Dual-energy CT, VOXSI, Voxelized CT scenario generator

Background. Use of highly conformal radiotherapy in patients with head and neck carcinoma may lead to under-/overdosage of gross target volume (GTV) and organs at risk (OAR) due to changes in patients’ anatomy. A method to achieve more effective radiation treatment combined with less toxicity is dose-guided radiotherapy (DGRT). The aim of this study was to evaluate discrepancies between planned and actually delivered radiation dose in head and neck patients and to identify predictive factors.Methods. In this retrospective analysis, 20 patients with cT2-4 N0-3 M0 carcinoma originating from oropharynx, oral cavity, larynx and hypopharynx (Cohort 1), and seven patients with cT1-4 N0-3 M0 nasopharyngeal carcinoma (Cohort 2) treated with primary (chemo)radiotherapy and undergoing weekly kV-CBCT scans were included. Radiation dose was recalculated on 184 kV-CBCT images, which was quantified by D95% (GTV), Dmean (parotid and submandibular glands) and D2% (spinal cord). Predictive factors investigated for changes in these dose metrics were: gender, age, cT/N-stage, tumor grade, HPV-status, systemic therapy, body mass index at start of treatment, weight loss and volume change over the duration of the radiotherapy.Results. There was no significant difference between the planned and delivered dose for GTV and OARs of Week 1 to subsequent weeks for Cohort 1. In Cohort 2, actually delivered Dmean to parotid glands was significant higher than planned dose (1.1 Gy, p = 0.002). No clinically relevant correlations between dose changes and predictive factors were found.Conclusion. Weekly dose calculations do not seem to improve dose delivery for patients with tumors of the oral cavity, oropharynx, larynx and hypopharynx. In patients with nasopharyngeal carcinoma, however, mid-treatment imaging may facilitate DGRT.

Purpose: The dose delivered with a HDR 192Ir afterloader can be separated into a dwell component, and a transit component resulting from the source movement. The transit component is directly dependent on the source speed profile and it is the goal of this study to measure accurate source speed profiles. Methods: A high speed video camera was used to record the movement of a 192 Ir source (Nucletron, an Elekta company, Stockholm, Sweden) for interdwell distances of 0.25–5 cm with dwell times of 0.1, 1, and 2 s. Transit dose distributions were calculated using a Monte Carlo code simulating the source movement. Results: The source stops at each dwell position oscillating around the desired position for a duration up to (0.026 ± 0.005) s. The source speed profile shows variations between 0 and 81 cm/s with average speed of ∼33 cm/s for most of the interdwell distances. The source stops for up to (0.005 ± 0.001) s at nonprogrammed positions in between two programmed dwell positions. The dwell time correction applied by the manufacturer compensates the transit dose between the dwell positions leading to a maximum overdose of 41 mGy for the considered cases and assuming an air-kerma strength of 48 000 U. The transit dose component is not uniformly distributed leading to over and underdoses, which is within 1.4% for commonly prescribed doses (3–10 Gy). Conclusions: The source maintains its speed even for the short interdwell distances. Dose variations due to the transit dose component are much lower than the prescribed treatment doses for brachytherapy, although transit dose component should be evaluated individually for clinical cases.

Brachytherapy is employed to treat a wide variety of cancers. However, an accurate treatment verification method is currently not available. This study describes a pre-treatment verification system that uses an imaging panel (IP) to verify important aspects of the treatment plan.A detailed modelling of the IP was only possible with an extensive calibration performed using a robotic arm. Irradiations were performed with a high dose rate (HDR) Ir-192 source within a water phantom. An empirical fit was applied to measure the distance between the source and the detector so 3D Cartesian coordinates of the dwell positions can be obtained using a single panel. The IP acquires 7.14 fps to verify the dwell times, dwell positions and air kerma strength (Sk). A gynecological applicator was used to create a treatment plan that was registered with a CT image of the water phantom used during the experiments for verification purposes. Errors (shifts, exchanged connections and wrong dwell times) were simulated to verify the proposed verification system.Cartesian source positions (panel measurement plane) have a standard deviation of about 0.02 cm. The measured distance between the source and the panel (z-coordinate) have a standard deviation up to 0.16 cm and maximum absolute error of approximate to 0.6 cm if the signal is close to sensitive limit of the panel. The average response of the panel is very linear with Sk. Therefore, Sk measurements can be performed with relatively small errors. The measured dwell times show a maximum error of 0.2 s which is consistent with the acquisition rate of the panel. All simulated errors were clearly identified by the proposed system.The use of IPs is not common in brachytherapy, however, it provides considerable advantages. It was demonstrated that the IP can accurately measure Sk, dwell times and dwell positions.

Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors. The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation fields in time.

This work aims at investigating intensity corrected cone-beam x-ray computed tomography (CBCT) images for accurate dose calculation in adaptive intensity modulated proton therapy (IMPT) for prostate and head and neck (HN) cancer. A deformable image registration (DIR)-based method and a scatter correction approach using the image data obtained from DIR as prior are characterized and compared on the basis of the same clinical patient cohort for the first time.Planning CT (pCT) and daily CBCT data (reconstructed images and measured projections) of four HN and four prostate cancer patients have been considered in this study. A previously validated Morphons algorithm was used for DIR of the planning CT to the current CBCT image, yielding a so-called virtual CT (vCT). For the first time, this approach was translated from HN to prostate cancer cases in the scope of proton therapy. The warped pCT images were also used as prior for scatter correction of the CBCT projections for both tumor sites. Single field uniform dose and IMPT (only for HN cases) treatment plans have been generated with a research version of a commercial planning system. Dose calculations on vCT and scatter corrected CBCT (CBCTA high agreement of vCT and CBCTFor HN patients, no considerable differences of vCT and CBCT

Imaging of patient anatomy during treatment is a necessity for position verification and for adaptive radiotherapy based on daily dose recalculation. Ultrasound (US) image guided radiotherapy systems are currently available to collect US images at the simulation stage (USsim), coregistered with the simulation computed tomography (CT), and during all treatment fractions. The authors hypothesize that a deformation field derived from US-based deformable image registration can be used to create a daily pseudo-CT (CTps) image that is more representative of the patients' geometry during treatment than the CT acquired at simulation stage (CTsim).The three prostate patients, considered to evaluate this hypothesis, had coregistered CT and US scans on various days. In particular, two patients had two US-CT datasets each and the third one had five US-CT datasets. Deformation fields were computed between pairs of US images of the same patient and then applied to the corresponding USsim scan to yield a new deformed CTps scan. The original treatment plans were used to recalculate dose distributions in the simulation, deformed and ground truth CT (CTgt) images to compare dice similarity coefficients, maximum absolute distance, and mean absolute distance on CT delineations and gamma index (γ) evaluations on both the Hounsfield units (HUs) and the dose.In the majority, deformation did improve the results for all three evaluation methods. The change in gamma failure for dose (γDose, 3%, 3 mm) ranged from an improvement of 11.2% in the prostate volume to a deterioration of 1.3% in the prostate and bladder. The change in gamma failure for the CT images (γCT, 50 HU, 3 mm) ranged from an improvement of 20.5% in the anus and rectum to a deterioration of 3.2% in the prostate.This new technique may generate CTps images that are more representative of the actual patient anatomy than the CTsim scan.

Purpose: As external beam treatment plans become more dynamic and the dose to normal tissue is further constrained, treatments may consist of a larger number of beams, each delivering smaller doses (or monitor units, MU), in, e.g., volumetric modulated arc therapy (VMAT). Electronic portal imaging devices(EPID) may be used to verify external beam treatments on integrated fractions as well as in a more time dependant manner such as field by field. For treatment verification performed during a fraction (e.g., individual fields or VMAT control points), the lower limit of EPID measurement capability becomes important. The authors quantified the signal and timing accuracy of EPIDimages for low MU intensity modulated radiotherapy(IMRT) and conformal fields. Methods: EPIDimages were collected from three different vendor's accelerators for low MU fields and compared to expected images. Simulations were performed to replicate the EPID acquisition pattern and to enhance the understanding of EPID readout schemes. Results: Large discrepancies between observed and predicted images were noted due to an under-response to single low MU fields. It is shown that a variability of up to 37% can be observed for low MU fields in clinically used EPID acquisition modes and that the majority of this variability can be accounted for by the readout scheme, integration, and timing of EPID acquisitions. Simulations have confirmed the causes of the discrepancies. The occurrence and extent of the variation has been estimated for clinical settings. Conclusions: Incorrect absolute EPID signals collected for low MU fields in external beam treatments will negatively affect quantitative applications such as individual field based EPIDdosimetry, typically appearing as an underdose, unless corrections to currently employed EPID readout schemes are made.

Purpose: Novel small animal precision microirradiators (micro-IR) are becoming available for preclinical use and are often equipped with onboard imaging (OBI) devices. We investigated the use of OBI as a means to infer the accuracy of the delivered treatment plan. Methods: Monte Carlo modeling of the micro-IR including an elliptical Gaussian electron beam incident on the x-ray tube was used to score dose and to continue photon transport to the plane of the OBI device. A model of the OBI detector response was used to generate simulated onboard images. Experimental OBI was performed at 225 kVp, gain/offset and scatter-glare were corrected. Simulated and experimentally obtained onboard images of phantoms and a mouse specimen were compared for a range of photon beam sizes from 2.5 cm down to 0.1 cm. Results: Simulated OBI can be used in small animal radiotherapy to determine if a treatment plan was delivered according to the prescription within an uncertainty of 5% for beams as small as 4 mm in diameter. For collimated beams smaller than 4 mm, beam profile differences remain primarily in the penumbra region of the smallest beams, which may be tolerable for specific preclinical micro-IR investigations. Conclusions: Comparing simulated to acquired OBI during small animal treatment radiotherapy represents a useful treatment delivery tool.

PURPOSE A widely accepted method to quantify differences in dose distributions is the gamma (gamma) evaluation. Currently, almost all gamma implementations utilize the central processing unit (CPU). Recently, the graphics processing unit (GPU) has become a powerful platform for specific computing tasks. In this study, we describe the implementation of a 3D gamma evaluation using a GPU to improve calculation time. METHODS The gamma evaluation algorithm was implemented on an NVIDIA Tesla C2050 GPU using the compute unified device architecture (CUDA). First, several cubic virtual phantoms were simulated. These phantoms were tested with varying dose cube sizes and set-ups, introducing artificial dose differences. Second, to show applicability in clinical practice, five patient cases have been evaluated using the 3D dose distribution from a treatment planning system as the reference and the delivered dose determined during treatment as the comparison. A calculation time comparison between the CPU and GPU was made with varying thread-block sizes including the option of using texture or global memory. RESULTS A GPU over CPU speed-up of 66 +/- 12 was achieved for the virtual phantoms. For the patient cases, a speed-up of 57 +/- 15 using the GPU was obtained. A thread-block size of 16 x 16 performed best in all cases. The use of texture memory improved the total calculation time, especially when interpolation was applied. Differences between the CPU and GPU gammas were negligible. CONCLUSIONS The GPU and its features, such as texture memory, decreased the calculation time for gamma evaluations considerably without loss of accuracy.

Purpose: We hypothesize that flattening filter free (FFF) high dose rate irradiation will decrease cell survival in normal and cancer cells with more pronounced effects in DNA repair deficient cells. Additionally, we hypothesize that removal of the flattening filter will result in an enhanced relative biological effectiveness independent of the dose rate.Materials and methods: Clonogenic survival was assessed after exposure to dose rates of 4 or 24 Gy/min (FFF 10 megavolt [MV] photon beam) using a Varian TrueBeam accelerator. Additionally, cells were exposed to 4 Gy/min with or without flattening filter. Relative biological effectiveness estimations were performed comparing the different beam photon spectra.Results: Cell survival in tumor and normal cell lines was not influenced by high dose rate irradiation. The intrinsic radiation sensitivity of DNA repair deficient cells was not affected by high dose rate compared to normal dose rate. Furthermore, the relative biological effectiveness was not significantly different from unity in any of the cell lines for both FFF and conventional flattened beam exposures.Conclusions: High dose rate irradiation did not affect long-term survival and DNA repair for cell lines of different tissues. This suggests that high dose rate does not influence treatment outcome or treatment toxicity and could be safely implemented in clinical routine.

Advancements made over the past decades in both molecular imaging and radiotherapy planning and delivery have enabled studies that explore the efficacy of heterogeneous radiation treatment ("dose painting") of solid cancers based on biological information provided by different imaging modalities. In addition to clinical trials, preclinical studies may help contribute to identifying promising dose painting strategies. The goal of this current study was twofold: to develop a reproducible positioning and set-up verification protocol for a rat tumor model to be imaged and treated on a clinical platform, and to assess the dosimetric accuracy of dose planning and delivery for both uniform and positron emission tomography-computed tomography (PET-CT) based heterogeneous dose distributions. We employed a syngeneic rat rhabdomyosarcoma model, which was irradiated by volumetric modulated arc therapy (VMAT) with uniform or heterogeneous 6 MV photon dose distributions. Mean dose to the gross tumor volume (GTV) as a whole was kept at 12 Gy for all treatment arms. For the nonuniform plans, the dose was redistributed to treat the 30% of the GTV representing the biological target volume (BTV) with a dose 40% higher than the rest of the GTV (GTV - BTV) (~15 Gy was delivered to the BTV vs. ~10.7 Gy was delivered to the GTV - BTV). Cone beam computed tomography (CBCT) images acquired for each rat prior to irradiation were used to correctly reposition the tumor and calculate the delivered 3D dose. Film quality assurance was performed using a water-equivalent rat phantom. A comparison between CT or CBCT doses and film measurements resulted in passing rates98% with a gamma criterion of 3%/2 mm using 2D dose images. Moreover, between the CT and CBCT calculated doses for both uniform and heterogeneous plans, we observed maximum differences of2% for mean dose to the tumor and mean dose to the biological target volumes. In conclusion, we have developed a robust method for dose painting in a rat tumor model on a clinical platform, with a high accuracy achieved in the delivery of complex dose distributions. Our work demonstrates the technical feasibility of this approach and enables future investigations on the therapeutic effect of preclinical dose painting strategies using a state-of-the-art clinical platform.

The dose delivered with a HDR (192)Ir afterloader can be separated into a dwell component, and a transit component resulting from the source movement. The transit component is directly dependent on the source speed profile and it is the goal of this study to measure accurate source speed profiles.A high speed video camera was used to record the movement of a (192)Ir source (Nucletron, an Elekta company, Stockholm, Sweden) for interdwell distances of 0.25-5 cm with dwell times of 0.1, 1, and 2 s. Transit dose distributions were calculated using a Monte Carlo code simulating the source movement.The source stops at each dwell position oscillating around the desired position for a duration up to (0.026 ± 0.005) s. The source speed profile shows variations between 0 and 81 cm/s with average speed of ∼ 33 cm/s for most of the interdwell distances. The source stops for up to (0.005 ± 0.001) s at nonprogrammed positions in between two programmed dwell positions. The dwell time correction applied by the manufacturer compensates the transit dose between the dwell positions leading to a maximum overdose of 41 mGy for the considered cases and assuming an air-kerma strength of 48 000 U. The transit dose component is not uniformly distributed leading to over and underdoses, which is within 1.4% for commonly prescribed doses (3-10 Gy).The source maintains its speed even for the short interdwell distances. Dose variations due to the transit dose component are much lower than the prescribed treatment doses for brachytherapy, although transit dose component should be evaluated individually for clinical cases.

Background. Geometric changes are frequent during the course of treatment of lung cancer patients. This may potentially result in deviations between the planned and actual delivered dose. Electronic portal imaging device (EPID)-based integrated transit planar portal dosimetry (ITPD) is a fast method for absolute in-treatment dose verification. The aim of this study was to investigate if ITPD could detect geometric changes in lung cancer patients.Materials and methods. A total of 460 patients treated with volumetric modulated arc therapy (VMAT) following daily cone beam computed tomography (CT)-based setup were visually inspected for geometrical changes on a daily basis. Forty-six patients were subject to changes and had a re-CT and an adaptive treatment plan. The reasons for adaptation were: change in atelectasis (n = 18), tumor regression (n = 9), change in pleural effusion (n = 8) or other causes (n = 11). The ITPDs were calculated on both the initial planning CT and the re-CT and compared with a global gamma (γ) evaluation (criteria: 3%\3mm). A treatment fraction failed when the percentage of pixels failing in the radiation fields exceeded 10%. Dose-volume histograms (DVHs) were compared between the initial plan versus the plan re-calculated on the re-CT.Results. The ITPD threshold method detected 76% of the changes in atelectasis, while only 50% of the tumor regression cases and 42% of the pleural effusion cases were detected. Only 10% of the cases adapted for other reasons were detected with ITPD. The method has a 17% false-positive rate. No significant correlations were found between changes in DVH metrics and γ fail-rates.Conclusions. This study showed that most cases with geometric changes caused by atelectasis could be captured by ITPD, however for other causes ITPD is not sensitive enough to detect the clinically relevant changes and no predictive power of ITPD was found.

Methods to calibrate Megavoltage electronic portal imaging devices (EPIDs) for dosimetry have been previously documented for dynamic treatments such as intensity modulated radiotherapy (IMRT) using flattened beams and typically using integrated fields. While these methods verify the accumulated field shape and dose, the dose rate and differential fields remain unverified. The aim of this work is to provide an accurate calibration model for time dependent pre-treatment dose verification using amorphous silicon (a-Si) EPIDs in volumetric modulated arc therapy (VMAT) for both flattened and flattening filter free (FFF) beams. A general calibration model was created using a Varian TrueBeam accelerator, equipped with an aS1000 EPID, for each photon spectrum 6 MV, 10 MV, 6 MV-FFF, 10 MV-FFF. As planned VMAT treatments use control points (CPs) for optimization, measured images are separated into corresponding time intervals for direct comparison with predictions. The accuracy of the calibration model was determined for a range of treatment conditions. Measured and predicted CP dose images were compared using a time dependent gamma evaluation using criteria (3%, 3 mm, 0.5 sec). Time dependent pre-treatment dose verification is possible without an additional measurement device or phantom, using the on-board EPID. Sufficient data is present in trajectory log files and EPID frame headers to reliably synchronize and resample portal images. For the VMAT plans tested, significantly more deviation is observed when analysed in a time dependent manner for FFF and non-FFF plans than when analysed using only the integrated field. We show EPID-based pre-treatment dose verification can be performed on a CP basis for VMAT plans. This model can measure pre-treatment doses for both flattened and unflattened beams in a time dependent manner which highlights deviations that are missed in integrated field verifications.

As external beam treatment plans become more dynamic and the dose to normal tissue is further constrained, treatments may consist of a larger number of beams, each delivering smaller doses (or monitor units, MU), in, e.g., volumetric modulated arc therapy (VMAT). Electronic portal imaging devices (EPID) may be used to verify external beam treatments on integrated fractions as well as in a more time dependent manner such as field by field. For treatment verification performed during a fraction (e.g., individual fields or VMAT control points), the lower limit of EPID measurement capability becomes important. The authors quantified the signal and timing accuracy of EPID images for low MU intensity modulated radiotherapy (IMRT) and conformal fields.EPID images were collected from three different vendor's accelerators for low MU fields and compared to expected images. Simulations were performed to replicate the EPID acquisition pattern and to enhance the understanding of EPID readout schemes.Large discrepancies between observed and predicted images were noted due to an under-response to single low MU fields. It is shown that a variability of up to 37% can be observed for low MU fields in clinically used EPID acquisition modes and that the majority of this variability can be accounted for by the readout scheme, integration, and timing of EPID acquisitions. Simulations have confirmed the causes of the discrepancies. The occurrence and extent of the variation has been estimated for clinical settings.Incorrect absolute EPID signals collected for low MU fields in external beam treatments will negatively affect quantitative applications such as individual field based EPID dosimetry, typically appearing as an underdose, unless corrections to currently employed EPID readout schemes are made.

Purpose: High Dose Rate (HDR) brachytherapy treatments are employed worldwide to treat a wide variety of cancers. However, in vivo dose verification remains a challenge with no commercial dosimetry system available to verify the treatment dose delivered to the patient. We propose a novel dosimetry system that couples an independent Monte Carlo (MC) simulation platform and an amorphous silicon Electronic Portal Imaging Device (EPID) to provide real time treatment verification. Methods: MC calculations predict the EPID response to the photon fluence emitted by the HDR source by simulating the patient, the source dwell positions and times, and treatment complexities such as tissue compositions/densities and different applicators. Simulated results are then compared against EPID measurements acquired with ∼0.14s time resolution which allows dose measurements for each dwell position. The EPID has been calibrated using an Ir-192 HDR source and experiments were performed using different phantoms, including tissue equivalent materials (PMMA, lung and bone). A source positioning accuracy of 0.2 mm, without including the afterloader uncertainty, was ensured using a robotic arm moving the source. Results: An EPID can acquire 3D Cartesian source positions and its response varies significantly due to differences in the material composition/density of the irradiated object, allowing detection of changes in patient geometry. The panel time resolution allows dose rate and dwell time measurements. Moreover, predicted EPID images obtained from clinical treatment plans provide anatomical information that can be related to the patient anatomy, mostly bone and air cavities, localizing the source inside of the patient using its anatomy as reference. Conclusion: Results obtained show the feasibility of the proposed dose verification system that is capable to verify all the brachytherapy treatment steps in real time providing data about treatment delivery quality and also applicator/structure motion during or between treatments.

Dose delivery of a radiotherapy treatment can be influenced by a number of factors. It has been demonstrated that the electronic portal imaging device (EPID) is valuable for transit portal dosimetry verification. Patient related dose differences can emerge at any time during treatment and can be categorized in two types: (1) systematic-appearing repeatedly, (2) random-appearing sporadically during treatment. The aim of this study is to investigate how systematic and random information appears in 2D transit dose distributions measured in the EPID plane over the entire course of a treatment and how this information can be used to examine interfractional trends, building toward a methodology to support adaptive radiotherapy. To create a trend overview of the interfractional changes in transit dose, the predicted portal dose for the different beams is compared to a measured portal dose using a gamma evaluation. For each beam of the delivered fraction, information is extracted from the gamma images to differentiate systematic from random dose delivery errors. From the systematic differences of a fraction for a projected anatomical structures, several metrics are extracted like percentage pixels with vertical bar gamma vertical bar > 1. We demonstrate for four example cases the trends and dose difference causes which can be detected with this method. Two sample prostate cases show the occurrence of a random and systematic difference and identify the organ that causes the difference. In a lung cancer case a trend is shown of a rapidly diminishing atelectasis (lung fluid) during the course of treatment, which was detected with this trend analysis method. The final example is a breast cancer case where we show the influence of set-up differences on the 2D transit dose. A method is presented based on 2D portal transit dosimetry to record dose changes throughout the course of treatment, and to allow trend analysis of dose discrepancies. We show in example cases that this method can identify the causes of dose delivery differences and that treatment adaptation can be triggered as a result. It provides an important element toward informed decision-making for adaptive radiotherapy.

A novel approach to read out radiochromic film was introduced recently by the manufacturer of GafChromic film. In this study, the performance of this triple-channel film dosimetry method was compared against the conventional single-red-channel film dosimetry procedure, with and without inclusion of a pre-irradiation (pre-IR) film scan, using EBT2 film and kilo-and megavoltage photon beams up to 10 Gy. When considering regions of interest averaged doses, the triple-channel method and both single-channel methods produced equivalent results. Absolute dose discrepancies between the triple-channel method, both single-channel methods and the treatment planning system calculated dose values, were no larger than 5 cGy for dose levels up to 2.2 Gy. Signal to noise in triple-channel dose images was found to be similar to signal to noise in single-channel dose images. The accuracy of resulting dose images from the triple-and single-channel methods with inclusion of pre-IR film scan was found to be similar. Results of a comparison of EBT2 data from a kilovoltage depth dose experiment to corresponding Monte Carlo depth dose data produced dose discrepancies of 9.5 +/- 12 cGy and 7.6 +/- 6 cGy for the single-channel method with inclusion of a pre-IR film scan and the triple-channel method, respectively. EBT2 showed to be energy sensitive at low kilovoltage energies with response differences of 11.9% and 15.6% in the red channel at 2 Gy between 50-225 kVp and 80-225 kVp photon spectra, respectively. We observed that the triple-channel method resulted in non-uniformity corrections of +/- 1% and consistency values of 0-3 cGy for the batches and dose levels studied. Results of this study indicate that the triple-channel radiochromic film read-out method performs at least as well as the single-channel method with inclusion of a pre-IR film scan, reduces film non-uniformity and saves time with elimination of a pre-IR film scan.

A widely accepted method to quantify differences in dose distributions is the gamma (gamma) evaluation. Currently, almost all gamma implementations utilize the central processing unit (CPU). Recently, the graphics processing unit (GPU) has become a powerful platform for specific computing tasks. In this study, we describe the implementation of a 3D gamma evaluation using a GPU to improve calculation time.The gamma evaluation algorithm was implemented on an NVIDIA Tesla C2050 GPU using the compute unified device architecture (CUDA). First, several cubic virtual phantoms were simulated. These phantoms were tested with varying dose cube sizes and set-ups, introducing artificial dose differences. Second, to show applicability in clinical practice, five patient cases have been evaluated using the 3D dose distribution from a treatment planning system as the reference and the delivered dose determined during treatment as the comparison. A calculation time comparison between the CPU and GPU was made with varying thread-block sizes including the option of using texture or global memory.A GPU over CPU speed-up of 66 +/- 12 was achieved for the virtual phantoms. For the patient cases, a speed-up of 57 +/- 15 using the GPU was obtained. A thread-block size of 16 x 16 performed best in all cases. The use of texture memory improved the total calculation time, especially when interpolation was applied. Differences between the CPU and GPU gammas were negligible.The GPU and its features, such as texture memory, decreased the calculation time for gamma evaluations considerably without loss of accuracy.

Purpose: During the course of radiotherapy the dose delivery can be influenced by a number of factors, e.g., anatomical changes over time. This can Result in discrepancies between planned and delivered dose. The electronic portal imaging device has been demonstrated to be valuable for 2D transit and 3D in‐vivo dose verification. The aim of this study was to investigate what type of patient‐related errors can be detected by quantifying the discrepancies based on 2D transit portal dosimetry. Methods: For 25 cancer patients treated with volumetric modulated arc therapy, changes were artificially introduced in the planning CT. The artificially introduced changes were: 1) Development and reduction of atelectasis in the lung; 2) weight loss and gain; 3) shift of the patient, and 4) base‐line shifts in anatomical structures. After introduction of the changes, 3D dose distributions were recalculated with the Eclipse treatment planning system and compared to the planned dose distribution using a 3D γ evaluation. The 2D portal dose images were predicted with in‐house developed algorithms and compared with 2D γ evaluation and dose difference maps. Results: Several of the introduced changes were found to lead to significant discrepancies in dose metrics derived from dose‐volume histograms or 3D γ distributions, which could also be detected by 2D transit portal dosimetry. Clear dose discrepancy trends over time were observed with increasing geometrical aberration. Conclusion: We have shown the relationship between 3D dose discrepancies and 2D portal dosimetry. Lower detection limits will be determined for the different anatomical changes introduced. This analysis may form the basis for decision making in adaptive radiotherapy.