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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. [ABSTRACT FROM PUBLISHER]

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 EPID images for low MU intensity modulated radiotherapy (IMRT) and conformal fields. Methods: 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. 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 EPID dosimetry, typically appearing as an underdose, unless corrections to currently employed EPID readout schemes are made. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: A widely accepted method to quantify differences in dose distributions is the gamma (γ) evaluation. Currently, almost all γ 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 γ evaluation using a GPU to improve calculation time.Methods: The γ 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 × 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 γs were negligible.Conclusions: The GPU and its features, such as texture memory, decreased the calculation time for γ evaluations considerably without loss of accuracy. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. A MABIS algorithm is developed, evaluated, and demonstrated in a preclinical small animal irradiation research workflow. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Dmeanto 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. [ABSTRACT FROM PUBLISHER]

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 192Ir 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 48000 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (?) 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 (Dose, 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 (CT, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To analyse the effect of different image reconstruction techniques on image quality and dual energy CT (DECT) imaging metrics. 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 (ρe) and effective atomic number (Zeff) values. Iterative reconstruction had favourable results for the DECT analysis: a significantly smaller spread for each material in the ρe-Zeff space and lower Zeff and ρe 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. 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. An iterative CBCT reconstruction platform was build using RTK. [ABSTRACT FROM AUTHOR]