Assessment of log-based fingerprinting system of Mobius3D with Elekta linear accelerators.

PURPOSE: The purpose of this study was to investigate the matching error that occurs when the Mobius3D fingerprinting system is applied in conjunction with an Elekta linear accelerator (LINAC) and to offer an acceptable and alternative method for circumventing this problem. MATERIAL AND METHODS: To avoid the multileaf collimator (MLC) conflicting error in the Mobius3D fingerprinting system, we developed an in-house program to move the MLC in the Digital Imaging and Communications in Medicine (DICOM) radiotherapy (RT)-Plan to pertinent positions, considering the relationship between log data and planned data. The re-delivered log files were calculated in the Mobius3D system, and the results were compared with those of corrected data (i.e., we analyzed a pair of re-collected log data and the previous DICOM RT-Plan data). The results were then evaluated by comparing several items, such as point dose errors, gamma index (GI) passing rates, and MLC root-mean-square (RMS) values. RESULTS: For the point dose error, the maximum difference found was below 2.0%. In the case of GI analysis of all plans, the maximum difference in the passing rates was below 1.4%. The statistical results obtained using a paired Student's t-test showed that there were no significant differences within the uncertainty. In the case of the RMS test, the maximum difference found was approximately 0.08 mm. CONCLUSIONS: Our results showed that all the mismatched log files were sufficiently acceptable within the uncertainty. We conclude that the matching error obtained when applying Mobius3D to an Elekta LINAC may be addressed using a simple modification of the fingerprinting system, and we expect that our study findings will help vendors resolve this issue in the near future.

Comparative performance analysis for abdominal phantom ROI detectability according to CT reconstruction algorithm: ADMIRE.

PURPOSE: We compared and analyzed the detectability performance pertaining to an abdominal phantom including a region of interest (ROI) according to a computed tomography (CT) reconstruction algorithm. METHODS: Three types of reconstruction algorithms (FBP, SAFIRE, and ADMIRE) were used to evaluate the detectability performance using the abdominal phantom (phantom size: 25 × 18 × 28 cm3 ). The vendor default settings for routine multi-detector computed tomography abdominal scans were used. As the quantitative evaluation method, the contrast-to-noise ratio (CNR), difference in coefficient of variation (COV) with the normalization based on the FBP data, and the noise power spectrum (NPS) were measured. RESULTS: The characteristic of the ADMIRE-3 reconstructed image was higher than those of the FBP and SAFIRE-3 reconstructed images. The CNR values of the SAFIRE and ADMIRE images were much higher than the corresponding values of the FBP images. The difference in COV values for the ADMIRE images was ~1.2 times lower than the corresponding values of the SAFIRE images. CONCLUSION: The comparative analysis of the abdominal phantom low-contrast resolution differences for each CT exposure parameters showed that ADMIRE demonstrated better results than SAFIRE and FBP in terms of contrast, CNR, COV difference, and 1D NPS. This indicates that ADMIRE can provide a clearer observation even with the same number of contrast objects as compared to SAFIRE and FBP owing to its better contrast resolution in the central part of the contrast hole at low kV.

Optimal planning strategy among various arc arrangements for prostate stereotactic body radiotherapy with volumetric modulated arc therapy technique.

BACKGROUND: The aim of this study was to determine the optimal strategy among various arc arrangements in prostate plans of stereotactic body radiotherapy with volumetric modulated arc therapy (SBRT-VMAT). PATIENTS AND METHODS: To investigate how arc arrangements affect dosimetric and biological metrics, SBRT-VMAT plans for eighteen patients were generated with arrangements of single-full arc (1FA), single-partial arc (1PA), double-full arc (2FA), and double-partial arc (2PA). All plans were calculated by the Acuros XB calculation algorithm. Dosimetric and radiobiological metrics for target volumes and organs at risk (OARs) were evaluated from dosevolume histograms. RESULTS: All plans were highly conformal (CI<1.05, CN=0.91) and homogeneous (HI=0.09-0.12) for target volumes. For OARs, there was no difference in the bladder dose, while there was a significant difference in the rectum and both femoral head doses. Plans using 1PA and 2PA showed a strong reduction to the mean rectum dose compared to plans using 1FA and 2FA. Contrastively, the D2% and mean dose in both femoral heads were always lower in plans using 1FA and 2FA. The average tumor control probability and normal tissue complication probability were comparable in plans using all arc arrangements. CONCLUSIONS: The use of 1PA had a more effective delivery time and produced equivalent target coverage with better rectal sparing, although all plans using four arc arrangements showed generally similar for dosimetric and biological metrics. However, the D2% and mean dose in femoral heads increased slightly and remained within the tolerance. Therefore, this study suggests that the use of 1PA is an attractive choice for delivering prostate SBRT-VMAT.

Comparison of Dosimetric Performance among Commercial Quality Assurance Systems for Verifying Pretreatment Plans of Stereotactic Body Radiotherapy Using Flattening-Filter-Free Beams.

The purpose of this study was to compare the performance of different commercial quality assurance (QA) systems for the pretreatment verification plan of stereotactic body radiotherapy (SBRT) with volumetric arc therapy (VMAT) technique using a flattening-filter-free beam. The verification for 20 pretreatment cancer patients (seven lung, six spine, and seven prostate cancers) were tested using three QA systems (EBT3 film, I'mRT MatriXX array, and MapCHECK). All the SBRT-VMAT plans were optimized in the Eclipse (version 11.0.34) treatment planning system (TPS) using the Acuros XB dose calculation algorithm and were delivered to the Varian TrueBeam® accelerator equipped with a high-definition multileaf collimator. Gamma agreement evaluation was analyzed with the criteria of 2% dose difference and 2 mm distance to agreement (2%/2 mm) or 3%/3 mm. The highest passing rate (99.1% for 3%/3 mm) was observed on the MapCHECK system while the lowest passing rate was obtained on the film. The pretreatment verification results depend on the QA systems, treatment sites, and delivery beam energies. However, the delivery QA results for all QA systems based on the TPS calculation showed a good agreement of more than 90% for both the criteria. It is concluded that the three 2D QA systems have sufficient potential for pretreatment verification of the SBRT-VMAT plan.

Dosimetric Effects of Magnetic Resonance Imaging-assisted Radiotherapy Planning: Dose Optimization for Target Volumes at High Risk and Analytic Radiobiological Dose Evaluation.

Based on the assumption that apparent diffusion coefficients (ADCs) define high-risk clinical target volume (aCTVHR) in high-grade glioma in a cellularity-dependent manner, the dosimetric effects of aCTVHR-targeted dose optimization were evaluated in two intensity-modulated radiation therapy (IMRT) plans. Diffusion-weighted magnetic resonance (MR) images and ADC maps were analyzed qualitatively and quantitatively to determine aCTVHR in a high-grade glioma with high cellularity. After confirming tumor malignancy using the average and minimum ADCs and ADC ratios, the aCTVHR with double- or triple-restricted water diffusion was defined on computed tomography images through image registration. Doses to the aCTVHR and CTV defined on T1-weighted MR images were optimized using a simultaneous integrated boost technique. The dosimetric benefits for CTVs and organs at risk (OARs) were compared using dose volume histograms and various biophysical indices in an ADC map-based IMRT (IMRTADC) plan and a conventional IMRT (IMRTconv) plan. The IMRTADC plan improved dose conformity up to 15 times, compared to the IMRTconv plan. It reduced the equivalent uniform doses in the visual system and brain stem by more than 10% and 16%, respectively. The ADC-based target differentiation and dose optimization may facilitate conformal dose distribution to the aCTVHR and OAR sparing in an IMRT plan.

Gamma analysis dependence on specified low-dose thresholds for VMAT QA.

The American Association of Physicists in Medicine Task Group 119 instructed institutions to use a low-dose threshold of 10% or a region of interest determined by the jaw setting when they collected gamma analysis quality assurance (QA) data for the planar dose distribution. However, there are no clinical data to quantitatively demonstrate the impact of the low-dose threshold on the gamma index. Therefore, we performed a gamma analysis with various low-dose thresholds in the range of 0% to 15% according to both global and local normalization and different acceptance criteria (3%/3 mm, 2%/2 mm, and 1%/1 mm). A total of 30 treatment plans--10 head and neck, 10 brain, and 10 prostate cancer cases--were randomly selected from the Varian Eclipse treatment planning system (TPS). For the gamma analysis, a calculated portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using an electronic portal-imaging device. Then, the gamma analysis was performed using the Portal Dosimetry software (Varian Medical Systems, Palo Alto, CA). The gamma passing rate (%GP) for the global normalization decreased as the low-dose threshold increased, and all low-dose thresholds led to %GP values above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for the local normalization, %GP for a low-dose threshold of 10% was 7.47%, 10.23%, and 6.71% greater than the low-dose threshold of 0% for head and neck, brain, and prostate for the 3%/3 mm criteria, respectively. The results indicate that applying the low-dose threshold to global normalization does not have a critical impact on patient-specific QA results. However, in the local normalization, the low-dose threshold level should be carefully selected because the excluded low-dose points could cause the average %GP to increase rapidly.

Comparison of VMAT-SABR treatment plans with flattening filter (FF) and flattening filter-free (FFF) beam for localized prostate cancer.

The purpose of this study is to investigate the feasibility of using a flattening filter-free (FFF) beam with an endorectal balloon for stereotactic ablative body radiotherapy (SABR) of clinically localized prostate cancer. We assessed plans of SABR with volumetric-modulated arc therapy (VMAT) that used a flattening filter (FF) beam and an FFF beam and compared the verification results of dosimetric quality assurance for all pretreatment plans. A total of 20 patients with prostate cancer were enrolled in the study. SABR plans using VMAT with two full arcs were optimized in the Eclipse treatment planning system. All plans prescribed 42.7 Gy in 7 fractions of 6.1 Gy each. Four SABR plans were computed for each patient: two with FF beams and two with FFF beams of 6 and 10 MV. For all plans, the cumulative dose-volume histograms (DVHs) for the target volumes and organs at risk (OARs) were recorded and compared. Pretreatment quality assurance (QA) was performed using the I'mRT MatriXX system and radiochromic EBT3 film to verify treatment delivery, and gamma analysis was used to quantify the agreement between calculations and measurements. In addition, total monitor units (MUs) and delivery time were investigated as technical parameters of delivery. All four plans achieved adequate dose conformity to the target volumes and had comparable dosimetric data. The DVHs of all four plans for each patient were very similar. All plans were highly conformal with CI < 1.05 and CN > 0.90, and the doses were homogeneous (HI = 0.08-0.15). Sparing for the bladder and rectum was slightly better with the 10 MV FF and FFF plans than with the 6 MV FF and FFF plans, but the difference was negligible. However, there was no significant difference in sparing for the other OARs. The mean agreement with the 3%/3 mm criterion was higher than 97% for verifying all plans. For the 2%/2 mm criterion, the corresponding agreement values were more than 90%, which showed that the plans were acceptable. The mean MUs and delivery time used were 1701 ± 101 and 3.02 ± 0.17 min for 6 MV FF, 1870 ± 116 and 2.01 ± 0.01 min for 6 MV FFF, 1471 ± 86 and 2.68 ± 0.14 min for 10 MV FF, and 1619 ± 101 and 2.00 ± 0.00 min for 10MV FFF, respectively. In the current study, the dose distributions of the prostate SABR plans using 6 and 10 MV FFF beams were similar to those using 6 and 10 MV FF beams. However, this study confirmed that SABR treatment using an FFF beam had an advantage with respect to delivery time. In addition, all pretreatment plans were verified as acceptable and their results were comparable. Therefore, the results of this study suggest that the use of an FFF beam for prostate SABR is a feasible and efficient technique, if carefully applied.

Generation of tissues outside the field of view (FOV) of radiation therapy simulation imaging based on machine learning and patient body outline (PBO).

BACKGROUND: It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning. METHODS: This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets. RESULTS: The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios). CONCLUSIONS: It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.

Enhancement of four-dimensional cone-beam computed tomography by compressed sensing with Bregman iteration.

In four-dimensional (4D) cone-beam computed tomography (CBCT), there is a spatio-temporal tradeoff that currently limits the accuracy. The aim of this study is to develop a Bregman iteration based formalism for high quality 4D CBCT image reconstruction from a limited number of low-dose projections. The 4D CBCT problem is first divided into multiple 3D CBCT subproblems by grouping the projection images corresponding to the phases. To maximally utilize the information from the under-sampled projection data, a compressed sensing (CS) method with Bregman iterations is employed for solving each subproblem. We formulate an unconstrained optimization problem based on least-square criterion regularized by total-variation. The least-square criterion reflects the inconsistency between the measured and the estimated line integrals. Furthermore, the unconstrained problem is updated and solved repeatedly by Bregman iterations. The performance of the proposed algorithm is demonstrated through a series of simulation studies and phantom experiments, and the results are compared to those of previously implemented compressed sensing technique using other gradient-based methods as well as conventional filtered back-projection (FBP) results. The simulation and experimental studies have shown that artifact suppressed images can be obtained with as small as 41 projections per phase, which is adequate for clinical 4D CBCT reconstruction. With such small number of projections, the conventional FDK failed to yield meaningful 4D CBCT images, and CS technique using conjugate gradient was not able to recover sharp edges. The proposed method significantly reduces the radiation dose and scanning time to achieve the high quality images compared to the 4D CBCT imaging based on the conventional FDK technique and the existing CS techniques.

A Mathematical Model for Predicting Patient Responses to Combined Radiotherapy with CTLA-4 Immune Checkpoint Inhibitors.

The purpose of this study was to develop a cell-cell interaction model that could predict a tumor's response to radiotherapy (RT) combined with CTLA-4 immune checkpoint inhibition (ICI) in patients with hepatocellular carcinoma (HCC). The previously developed model was extended by adding a new term representing tremelimumab, an inhibitor of CTLA-4. The distribution of the new immune activation term was derived from the results of a clinical trial for tremelimumab monotherapy (NCT01008358). The proposed model successfully reproduced longitudinal tumor diameter changes in HCC patients treated with tremelimumab (complete response = 0%, partial response = 17.6%, stable disease = 58.8%, and progressive disease = 23.6%). For the non-irradiated tumor control group, adding ICI to RT increased the clinical benefit rate from 8% to 32%. The simulation predicts that it is beneficial to start CTLA-4 blockade before RT in terms of treatment sequences. We developed a mathematical model that can predict the response of patients to the combined CTLA-4 blockade with radiation therapy. We anticipate that the developed model will be helpful for designing clinical trials with the ultimate aim of maximizing the efficacy of ICI-RT combination therapy.

Fast compressed sensing-based CBCT reconstruction using Barzilai-Borwein formulation for application to on-line IGRT.

PURPOSE: Compressed sensing theory has enabled an accurate, low-dose cone-beam computed tomography (CBCT) reconstruction using a minimal number of noisy projections. However, the reconstruction time remains a significant challenge for practical implementation in the clinic. In this work, we propose a novel gradient projection algorithm, based on the Gradient-Projection-Barzilai-Borwein formulation (GP-BB), that handles the total variation (TV)-norm regularization-based least squares problem for the CBCT reconstruction in a highly efficient manner, with speed acceptable for routine use in the clinic. METHODS: CBCT is reconstructed by minimizing an energy function consisting of a data fidelity term and a TV-norm regularization term. Both terms are simultaneously minimized by calculating the gradient projection of the energy function with the step size determined using an approximate Hessian calculation at each iteration, based on the Barzilai-Borwein formulation. To speed up the process, a multiresolution optimization is used. In addition, the entire algorithm was designed to run with a single graphics processing unit (GPU) card. To evaluate the performance, the Shepp-Logan numerical phantom, the CatPhan 600 physical phantom, and a clinically-treated head-and-neck patient were acquired from the TrueBeam™ system (Varian Medical Systems, Palo Alto, CA). For each scan, in total, 364 projections were acquired in a 200° rotation. The imager has 1024 × 768 pixels with 0.388 × 0.388-mm resolution. This was down-sampled to 512 × 384 pixels with 0.776 × 0.776-mm resolution for reconstruction. Evenly spaced angles were subsampled and used for varying the number of projections for the image reconstruction. To assess the performance of our GP-BB algorithm, we have implemented and compared with three compressed sensing-type algorithms, the two of which are popular and published (forward-backward splitting techniques), and the other one with a basic line-search technique. In addition, the conventional Feldkamp-Davis-Kress (FDK) reconstruction of the clinical patient data is compared as well. RESULTS: In comparison with the other compressed sensing-type algorithms, our algorithm showed convergence in ≤30 iterations whereas other published algorithms need at least 50 iterations in order to reconstruct the Shepp-Logan phantom image. With the CatPhan phantom, the GP-BB algorithm achieved a clinically-reasonable image with 40 projections in 12 iterations, in less than 12.6 s. This is at least an order of magnitude faster in reconstruction time compared with the most recent reports utilizing GPU technology given the same input projections. For the head-and-neck clinical scan, clinically-reasonable images were obtained from 120 projections in 34-78 s converging in 12-30 iterations. In this reconstruction range (i.e., 120 projections) the image quality is visually similar to or better than the conventional FDK reconstructed images using 364 projections. This represents a dose reduction of nearly 67% (120∕364 projections) while maintaining a reasonable speed in clinical implementation. CONCLUSIONS: In this paper, we proposed a novel, fast, low-dose CBCT reconstruction algorithm using the Barzilai-Borwein step-size calculation. A clinically viable head-and-neck image can be obtained within ∼34-78 s while simultaneously cutting the dose by approximately 67%. This makes our GP-BB algorithm potentially useful in an on-line image-guided radiation therapy (IGRT).

Effect of jaw size in megavoltage CT on image quality and dose.

PURPOSE: Recently, the jaw size for the TomoTherapy Hi-Art II(®) (TomoTherapy Inc., Madison, WI) was reduced from 4 mm (J4) to 1 mm (J1) to improve the longitudinal (IEC-Y) resolution in megavoltage computed tomography (MVCT) images. This study evaluated the effect of jaw size on the image quality and dose, as well as the dose delivered to the lens of the eye, which is a highly radiosensitive tissue. METHODS: MVCT image quality (image noise, uniformity, contrast linearity, high-contrast resolution, and full width at half-maximum) and multiple scan average dose (MSAD) were measured at different jaw sizes. A head phantom and photoluminescence glass dosimeters (PLDs) were used to measure the exposed lens dose (cGy). Different MVCT scan modes (pitch = 1, 2, and 3) and scan lengths (108 mm, 156 mm, and 204 mm) were applied in the MSAD and PLDs measurements. RESULTS: The change in jaw size from J4 to J1 produced no change or only a slight improvement in image noise, uniformity, contrast linearity, and high-contrast resolution. However, the full-width at half-maximum reduced from approximately 7.2 at J4 to 4.5 mm at J1, which represents an enhancement in the longitudinal resolution. The MSAD at the center point changed from approximately 0.69-2.32 cGy (peripheral: 0.83-2.49 cGy) at J4 to 0.85-2.81 cGy (peripheral: 1.05-2.86 cGy) at J1. The measured lens dose increased from 0.92-3.36 cGy at J4 to 1.06-3.91 cGy at J1. CONCLUSIONS: The change in jaw size improved longitudinal resolution. The MVCT imaging dose of approximately 3.86 cGy, 1.92 cGy, and 1.22 cGy was delivered at a pitch of 1, 2, and 3, respectively, per fraction in the head and neck treatment plans. Therefore, allowance for an approximately 15% increase in lens dose over that with J4 should be provided with J1.

Quantitative Assessment of the Restoration of Original Anatomy after 3D Virtual Reduction of Long Bone Fractures.

Background: The purpose of this study was to demonstrate the usefulness of 3D image-based virtual reduction by validating the evaluation criteria according to guidelines suggested by the AO Surgery Reference. Methods: For this experiment, 19 intact radial ORTHObones (ORTHObones radius, 3B Scientific, Germany, Hamburg) without any fractures were prepared. All ORTHObones with six cortical marking holes (three points on the distal part and three points on the proximal part) were scanned using a CT scanner twice (before/after intentional fracture of the ORTHObone). After the virtual reduction of all 19 ORTHObones, accuracy evaluations using the four criteria (length variation, apposition variation, alignment variation, Rotation Variation) suggested in the AO Surgery Reference were performed. Results: The mean (M) length variation was 0.42 mm, with 0.01 mm standard deviation (SD). The M apposition variation was 0.48 mm, with 0.40 mm SD. The M AP angulation variation (for alignment variation) was 3.24°, with 2.95° SD. The M lateral angulation variation (for alignment variation) was 0.09°, with 0.13° SD. The M angle of axial rotation was 1.27° with SD: 1.19°. Conclusions: The method of accuracy evaluation used in this study can be helpful in establishing a reliable plan.

A multivariate approach to determine electron beam parameters for a Monte Carlo 6 MV Linac model: Statistical and machine learning methods.

PURPOSE: This study aimed to determine the optimal initial electron beam parameters of a Linac for radiotherapy with a multivariate approach using statistical and machine-learning tools. METHODS: For MC beam commissioning, a 6 MV Varian Clinac was simulated using the Geant4 toolkit. The authors investigated the relations between simulated dose distribution and initial electron beam parameters, namely, mean energy (E), energy spread (ES), and radial beam size (RS). The goodness of simulation was evaluated by the slope of differences between the simulated and the golden beam data. The best-fit combination of the electron beam parameters that minimized the slope of dose difference was searched through multivariate methods using conventional statistical methods and machine-learning tools of the scikit-learn library. RESULTS: Simulation results with 87 combinations of the electron beam parameters were analyzed. Regardless of being univariate or multivariate, traditional statistical models did not recommend a single parameter set simultaneously minimizing slope of dose differences for percent depth dose (PDD) and lateral dose profile (LDP). Two machine learning classification modules, RandomForestClassifier and BaggingClassifier, agreed in recommending (E = 6.3 MeV, ES = ±5.0%, RS = 1.0 mm) for predicting simultaneous acceptance of PDD and LDP. CONCLUSIONS: The machine learning with random-forest and bagging classifier modules recommended a consistent result. It was possible to draw an optimal electron beam parameter set using multivariate methods for MC simulation of a radiotherapy 6 MV Linac.

Mechanical and Biocompatibility Properties of Sintered Titanium Powder for Mimetic 3D-Printed Bone Scaffolds.

A composite comprising Ti and NaCl powders was sintered similar to a three-dimensional (3D)-printed patient-customized artificial bone scaffold. Additionally, a proper microstructure of the mimetic scaffold and the optimum processing parameters for its development were analyzed. The mechanical properties of the metal-based porous-structured framework used as an artificial bone scaffold were an optimum replacement for the human bone. Thus, it was confirmed that patient-customized scaffolds could be manufactured via 3D printing. The 3D-printed mimetic specimens were fabricated by a powder-sintering method using Ti for the metal parts, NaCl as the pore former, and polylactic acid as the biodegradable binder. Scanning electron microscopy (SEM) images showed that pores were formed homogeneously, while X-ray computed tomography confirmed that open pores were generated. The porosity and pore size distribution were measured using a mercury porosimeter, while the flexural strength and flexural elastic modulus were calculated using the three-point bending test. Based on these measurements, a pore-former content of 15 vol % optimized the density and flexural strength to 2.52 g cm-2 and 283 MPa, respectively, similar to those of the actual iliac bone. According to the 3D-printing production method, a selective laser-sintering process was applied for the fabrication of the mimetic specimen, and it was determined that the microstructure and properties similar to those of previous metal specimens could be achieved in the as-prepared specimen. Additionally, a decellularized extracellular matrix (dECM) was used to coat the surfaces and interiors of the specimens for evaluating their biocompatibilities. SEM image analysis indicated that the adipose-derived stem cells grew evenly inside the pores of the coated specimens, as compared with the bulky Ti specimens without the dECM coating. The doubling time at 65% was measured at 72, 75, and 83 h for specimens with pore-former contents of 5, 10, and 15 vol %, respectively. The doubling time without the pore former was 116 h. As compared with the specimens without the pore former (73 h), 15% of the dECM-coated specimens showed a doubling time of 64%, measured at 47 h.

Inverse planning for IMRT with nonuniform beam profiles using total-variation regularization (TVR).

PURPOSE: Radiation therapy with high dose rate and flattening filter-free (FFF) beams has the potential advantage of greatly reduced treatment time and out-of-field dose. Current inverse planning algorithms are, however, not customized for beams with nonuniform incident profiles and the resultant IMRT plans are often inefficient in delivery. The authors propose a total-variation regularization (TVR)-based formalism by taking the inherent shapes of incident beam profiles into account. METHODS: A novel TVR-based inverse planning formalism is established for IMRT with nonuniform beam profiles. The authors introduce a TVR term into the objective function, which encourages piecewise constant fluence in the nonuniform FFF fluence domain. The proposed algorithm is applied to lung and prostate and head and neck cases and its performance is evaluated by comparing the resulting plans to those obtained using a conventional beamlet-based optimization (BBO). RESULTS: For the prostate case, the authors' algorithm produces acceptable dose distributions with only 21 segments, while the conventional BBO requires 114 segments. For the lung case and the head and neck case, the proposed method generates similar coverage of target volume and sparing of the organs-at-risk as compared to BBO, but with a markedly reduced segment number. CONCLUSIONS: TVR-based optimization in nonflat beam domain provides an effective way to maximally leverage the technical capacity of radiation therapy with FFF fields. The technique can generate effective IMRT plans with improved dose delivery efficiency without significant deterioration of the dose distribution.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PURPOSE: In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. METHODS: The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. RESULTS: The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. CONCLUSIONS: The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

Multisource modeling of flattening filter free (FFF) beam and the optimization of model parameters.

PURPOSE: With the introduction of flattening filter free (FFF) linear accelerators to radiation oncology, new analytical source models for a FFF beam applicable to current treatment planning systems is needed. In this work, a multisource model for the FFF beam and the optimization of involved model parameters were designed. METHODS: The model is based on a previous three source model proposed by Yang et al. ["A three-source model for the calculation of head scatter factors," Med. Phys. 29, 2024-2033 (2002)]. An off axis ratio (OAR) of photon fluence was introduced to the primary source term to generate cone shaped profiles. The parameters of the source model were determined from measured head scatter factors using a line search optimization technique. The OAR of the photon fluence was determined from a measured dose profile of a 40 x 40 cm2 field size with the same optimization technique, but a new method to acquire gradient terms for OARs was developed to enhance the speed of the optimization process. The improved model was validated with measured dose profiles from 3 x 3 to 40 x 40 cm2 field sizes at 6 and 10 MV from a TrueBeam STx linear accelerator. Furthermore, planar dose distributions for clinically used radiation fields were also calculated and compared to measurements using a 2D array detector using the gamma index method. RESULTS: All dose values for the calculated profiles agreed with the measured dose profiles within 0.5% at 6 and 10 MV beams, except for some low dose regions for larger field sizes. A slight overestimation was seen in the lower penumbra region near the field edge for the large field sizes by 1%-4%. The planar dose calculations showed comparable passing rates (> 98%) when the criterion of the gamma index method was selected to be 3%/3 mm. CONCLUSIONS: The developed source model showed good agreements between measured and calculated dose distributions. The model is easily applicable to any other linear accelerator using FFF beams as the required data include only the measured PDD, dose profiles, and output factors for various field sizes, which are easily acquired during conventional beam commissioning process.

Development of a novel quality assurance system based on rolled-up and rolled-out radiochromic films in volumetric modulated arc therapy.

PURPOSE: To develop a cylindrical phantom with rolled-up radiochromic films and dose analysis software in the rolled-out plane for quality assurance (QA) in volumetric modulated arc therapy (VMAT). METHODS: The phantom consists of an acrylic cylindrical body wrapped with radiochromic film inserted into an outer cylindrical shell of 5 cm thickness. The rolled-up films with high spatial resolution enable detection of specific dose errors along the arc trajectory of continuously irradiated and modulated beams in VMAT. The developed dose analysis software facilitates dosimetric evaluation in the rolled-up and rolled-out planes of the film; the calculated doses on the corresponding points where the rolled-up film was placed were reconstructed into a rectangular dose matrix equivalent to that of the rolled-out plane of the film. The VMAT QA system was implemented in 3 clinical cases of prostate, nasopharynx, and pelvic metastasis. Each calculated dose on the rolled-out plane was compared with measurement values by modified gamma evaluation. Detected positions of dose disagreement on the rolled-out plane were also distinguished in cylindrical coordinates. The frequency of error occurrence and error distribution were summarized in a histogram and in an axial view of rolled-up plane to intuitively identify the corresponding positions of detected errors according to the gantry angle. RESULTS: The dose matrix reconstructed from the developed VMAT QA system was used to verify the measured dose distribution along the arc trajectory. Dose discrepancies were detected on the rolled-out plane and visualized on the calculated dose matrix in cylindrical coordinates. The error histogram obtained by gamma evaluation enabled identification of the specific error frequency at each gantry angular position. The total dose error occurring on the cylindrical surface was in the range of 5%-8% for the 3 cases. CONCLUSIONS: The developed system provides a practical and reliable QA method to detect dosimetric errors according to the gantry angle. Film dosimetry based on rolled-up and rolled-out techniques leads to dose verification in the subspaces of the 3D dose volume. The system can be employed as an alternative tool to detect the pitfalls of planar dose verification.

Application of the gamma evaluation method in Gamma Knife film dosimetry.

PURPOSE: Gamma Knife (GK) radiosurgery is a minimally invasive surgical technique for the treatment of intracranial lesions. To minimize neurological deficits, submillimeter accuracy is required during treatment delivery. In this paper, the delivery accuracy of GK radiosurgery was assessed with the gamma evaluation method using planning dose distribution and film measurement data. METHODS: Single 4, 8, and 16 mm and composite shot plans were developed for evaluation using the GK Perfexion (PFX) treatment planning system (TPS). The planning dose distributions were exported as digital image communications in medicine - radiation therapy (DICOM RT) files using a new function of GK TPS. A maximum dose of 8 Gy was prescribed for four test plans. Irradiation was performed onto a spherical solid water phantom using Gafchromic EBT2 films in the axial and coronal planes. The exposed films were converted to absolute dose based on a 4th-order polynomial calibration curve determined using ten calibration films. The film measurement results and planning dose distributions were registered for further analysis in the same Leksell coordinate using in-house software. The gamma evaluation method was applied to two dose distributions with varying spatial tolerance (0.3-2.0 mm) and dosimetric tolerance (0.3-2.0%), to verify the accuracy of GK radiosurgery. The result of gamma evaluation was assessed using pass rate, dose gamma index histogram (DGH), and dose pass rate histogram (DPH). RESULTS: The 20, 50, and 80% isodose lines found in film measurements were in close agreement with the planning isodose lines, for all dose levels. The comparison of diagonal line profiles across the axial plane yielded similar results. The gamma evaluation method resulted in high pass rates of >95% within the 50% isodose line for 0.5 mm∕0.5% tolerance criteria, in both the axial and coronal planes. They satisfied 1.0 mm∕1.0% criteria within the 20% isodose line. Our DGH and DPH also showed that low isodose lines exhibited inferior gamma indexes and pass rates compared with higher isodose lines. CONCLUSIONS: The gamma evaluation method was applicable to GK radiosurgery. For all test plans, planning dose distribution and film measurement met the tolerance criteria of 0.5 mm∕0.5% within the 50% isodose line which are used for marginal dose prescription.