SynthRAD2023 Grand Challenge dataset: Generating synthetic CT for radiotherapy.

PURPOSE: Medical imaging has become increasingly important in diagnosing and treating oncological patients, particularly in radiotherapy. Recent advances in synthetic computed tomography (sCT) generation have increased interest in public challenges to provide data and evaluation metrics for comparing different approaches openly. This paper describes a dataset of brain and pelvis computed tomography (CT) images with rigidly registered cone-beam CT (CBCT) and magnetic resonance imaging (MRI) images to facilitate the development and evaluation of sCT generation for radiotherapy planning. ACQUISITION AND VALIDATION METHODS: The dataset consists of CT, CBCT, and MRI of 540 brains and 540 pelvic radiotherapy patients from three Dutch university medical centers. Subjects' ages ranged from 3 to 93 years, with a mean age of 60. Various scanner models and acquisition settings were used across patients from the three data-providing centers. Details are available in a comma separated value files provided with the datasets. DATA FORMAT AND USAGE NOTES: The data is available on Zenodo (https://doi.org/10.5281/zenodo.7260704, https://doi.org/10.5281/zenodo.7868168) under the SynthRAD2023 collection. The images for each subject are available in nifti format. POTENTIAL APPLICATIONS: This dataset will enable the evaluation and development of image synthesis algorithms for radiotherapy purposes on a realistic multi-center dataset with varying acquisition protocols. Synthetic CT generation has numerous applications in radiation therapy, including diagnosis, treatment planning, treatment monitoring, and surgical planning.

Comparing adaptation strategies in MRI-guided online adaptive radiotherapy for prostate cancer: Implications for treatment margins.

PURPOSE: To quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV). MATERIALS AND METHODS: Clinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0-5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions. RESULTS: The PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm. CONCLUSION: ATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations.

Single-spoke binning: Reducing motion artifacts in abdominal radial stack-of-stars imaging.

PURPOSE: To increase the effectiveness of respiratory gating in radial stack-of-stars MRI, particularly when imaging at high spatial resolutions or with multiple echoes. METHODS: Free induction decay (FID) navigators were integrated into a three-dimensional gradient echo radial stack-of-stars pulse sequence. These navigators provided a motion signal with a high temporal resolution, which allowed single-spoke binning (SSB): each spoke at each phase encode step was sorted individually to the corresponding motion state of the respiratory signal. SSB was compared with spoke-angle binning (SAB), in which all phase encode steps of one projection angle were sorted without the use of additional navigator data. To illustrate the benefit of SSB over SAB, images of a motion phantom and of six free-breathing volunteers were reconstructed after motion-gating using either method. Image sharpness was quantitatively compared using image gradient entropies. RESULTS: The proposed method resulted in sharper images of the motion phantom and free-breathing volunteers. Differences in gradient entropy were statistically significant (p = 0.03) in favor of SSB. The increased accuracy of motion-gating led to a decrease of streaking artifacts in motion-gated four-dimensional reconstructions. To consistently estimate respiratory signals from the FID-navigator data, specific types of gradient spoiler waveforms were required. CONCLUSION: SSB allowed high-resolution motion-corrected MR imaging, even when acquiring multiple gradient echo signals or large acquisition matrices, without sacrificing accuracy of motion-gating. SSB thus relieves restrictions on the choice of pulse sequence parameters, enabling the use of motion-gated radial stack-of-stars MRI in a broader domain of clinical applications.

A margin recipe for the management of intra-fraction target motion in radiotherapy.

Background and purpose: Strategies to limit the impact of intra-fraction motion during treatment are common in radiotherapy. Margin recipes, however, are not designed to incorporate these strategies. This work aimed to provide a framework to determine how motion management strategies influence treatment margins. Materials and methods: Two models of intra-fraction motion were considered. In model 1 motion was instantaneous, before treatment starts and in model 2 motion was a continuous drift during treatment. Motion management strategies were modelled by truncating the underlying error distribution at cσ, with σ the standard deviation of the distribution and c a free parameter. Using Monte Carlo simulations, we determined how motion management changed the required margin. The analysis was performed for different number of treatment fractions and different standard deviations of the underlying random and systematic errors. Results: The required margin for a continuous drift was found to be well approximated by an average position of the target at ¾ of the drift. Introducing a truncation at cσ, the relative change in the margin was equal to 0.3c. This result held for both models, was independent of σ or the number of fractions and naturally generalizes to the situation with a residual (systematic) error. Conclusion: Treatment margins can be determined when motion management strategies are applied. Moreover, our analysis can be used to study the potential benefit of different motion management strategies. This allows to discuss and determine the most appropriate strategy for margin reduction.

Adaptive margins for online adaptive radiotherapy.

Objective.In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for a planning target volume margin that does not need to be constant over the whole course of treatment, as is the case in conventional radiotherapy. This work aims to introduce an approach to update the margins each fraction based on the per-patient treatment history and explore the potential benefits of such adaptive margins.Approach.We introduce a novel methodology to implement adaptive margins, isotropic and anisotropic, during a treatment course based on the accumulated dose to the CTV. We then simulate treatment histories for treatments delivered in up to 20 fractions using various choices for the standard deviations of the systematic and random errors and homogeneous and inhomogeneous dose distributions. The treatment-averaged adaptive margin was compared to standard constant margins. The change in the minimum dose delivered to the CTV was compared on a patient and a population level. All simulations were performed within the van Herk approach and its known limitations.Main results.The population mean treatment-averaged margins are down to 70% and 55% of the corresponding necessary constant margins for the isotropic and anisotropic approach. The reduction increases with longer fractionation schemes and an inhomogeneous target dose distribution. Most of the benefit can be attributed to the elimination of the effective systematic error over the course of treatment. Interpatient differences in treatment-averaged margins were largest for the isotropic margins. For the 10% of patients that would receive a lower than prescribed dose to the CTV this minimum dose to the CTV is increased using the adaptive margin approaches.Significance.Adaptive margins can allow to reduce margins in most patients without compromising patients with greater than average target motion.

Predicting patient specific Pareto fronts from patient anatomy only.

PURPOSE: To demonstrate the feasibility of predicting the patient-specific treatment planning Pareto front (PF) for prostate cancer patients based only on delineations of PTV, rectum and body. MATERIAL/METHODS: Our methodology consists of four steps. First, using Erasmus-iCycle, the Pareto fronts of 112 prostate cancer patients were constructed by generating per patient 42 Pareto optimal treatment plans with different priorities. Dose parameters associated to homogeneity, conformity and dose to rectum were extracted. Second, a 3D convex function representing the PF spanned by the 42 plans was fitted for each patient using three patient-specific parameters. Third, ten features were extracted from the, aforementioned, structures to train a linear-regressor prediction algorithm to predict these three patient-specific parameters. Fourth, the quality of the predictions was assessed by calculating the average and maximum distances of the predicted PF to the 42 plans for patients in the validation cohort. RESULTS: The prediction model was able to predict the clinically relevant PF within 2 Gy for 90% of the patients with a median average distance of 0.6 Gy. CONCLUSIONS: We demonstrate the feasibility of fast, accurate predictions of the patient-specific PF for prostate cancer patients based only on delineations of PTV, rectum and body.

Clinical workflow for treating patients with a metallic hip prosthesis using magnetic resonance imaging-guided radiotherapy.

BACKGROUND & PURPOSE: Metallic prostheses distort the magnetic field during magnetic resonance imaging (MRI), leading to geometric distortions and signal loss. The purpose of this work was to develop a method to determine eligibility for MRI-guided radiotherapy (MRIgRT) on a per patient basis by estimating the magnitude of geometric distortions inside the clinical target volume (CTV). MATERIALS & METHODS: Three patients with prostate cancer and hip prosthesis, treated using MRIgRT, were included. Eligibility for MRIgRT was based on computed tomography and associated CTV delineations, together with a field-distortion (B0) map and anatomical images acquired during MR simulation. To verify the method, B0 maps made during MR simulation and each MRIgRT treatment fraction were compared. RESULTS: Estimates made during MR simulation of the magnitude of distortions inside the CTV were 0.43 mm, 0.19 mm and 2.79 mm compared to the average over all treatment fractions of 1.40 mm, 0.32 mm and 1.81 mm, per patient respectively. CONCLUSIONS: B0 map acquisitions prior to treatment can be used to estimate the magnitude of distortions during MRIgRT to guide the decision on eligibility for MRIgRT of prostate cancer patients with metallic hip implants.

SBRT combined with concurrent chemoradiation in stage III NSCLC: Feasibility study of the phase I Hybrid trial.

PURPOSE: To assess the technical and clinical feasibility of the phase I Hybrid trial (NCT01933568), combining SBRT of the primary tumor (PT) and fractionated radiotherapy (FRT) to the lymph nodes (LN). MATERIALS AND METHODS: Ten patients with stage III NSCLC with a peripheral PT < 5 cm were prospectively selected. The EQD2 corrected normal tissue dose parameters of the FRT plan of 24×2.75 Gy to PT and 24×2.42 Gy to LN (IMRT) was compared with 3×18 Gy on the PT and 24×2.42 Gy on the LN (VMAT) using a Wilcoxon signed-rank test. To anticipate differential motion between PT and LN, worst-case scenarios for OAR were calculated. Electronic portal imaging device (EPID) dosimetry analysis was performed to rule out dosimetric errors during delivery. RESULTS: The Hybrid plans revealed a significant decrease of esophagus EUD n = 0.13, lung V5 and V20 and a significant increase in Dmax of the PRV of the mediastinal envelope. Plans were robust against differential motion of 5 mm between PT and LN in 8 patients and failed in 2 patients due to spinal cord constraints. Average pass rates were ≥87% for EPID dosimetry. CONCLUSIONS: SBRT and FRT could be combined within the given OAR constraints. Safety will be assessed in the Hybrid trial.

Correcting geometric image distortions in slice-based 4D-MRI on the MR-linac.

PURPOSE: The importance of four-dimensional-magnetic resonance imaging (4D-MRI) is increasing in guiding online plan adaptation in thoracic and abdominal radiotherapy. Many 4D-MRI sequences are based on multislice two-dimensional (2D) acquisitions which provide contrast flexibility. Intrinsic to MRI, however, are machine- and subject-related geometric image distortions. Full correction of slice-based 4D-MRIs acquired on the Unity MR-linac (Elekta AB, Stockholm, Sweden) is challenging, since through-plane corrections are currently not available for 2D sequences. In this study, we implement a full three-dimensional 3D correction and quantify the geometric and dosimetric effects of machine-related (residual) geometric image distortions. METHODS: A commercial three-dimensional (3D) geometric QA phantom (Philips, Best, the Netherlands) was used to quantify the effect of gradient nonlinearity (GNL) and static-field inhomogeneity (B0I) on geometric accuracy. Additionally, the effectiveness of 2D (in-plane, machine-generic), 3D (machine-generic), and in-house developed 3D + (machine-specific) corrections was investigated. Corrections were based on deformable vector fields derived from spherical harmonics coefficients. Three patients with oligometastases in the liver were scanned with axial 4D-MRIs on our MR-linac (total: 10 imaging sessions). For each patient, a step-and-shoot IMRT plan (3 × 20 Gy) was created based on the simulation mid-position (midP)-CT. The 4D-MRIs were then warped into a daily midP-MRI and geometrically corrected. Next, the treatment plan was adapted according to the position offset of the tumor between midP-CT and the 3D-corrected midP-MRIs. The midP-CT was also deformably registered to the daily midP-MRIs (different corrections applied) to quantify the dosimetric effects of (residual) geometric image distortions. RESULTS: Using phantom data, median GNL distortions were 0.58 mm (no correction), 0.42-0.48 mm (2D), 0.34 mm (3D), and 0.34 mm (3D + ), measured over a diameter of spherical volume (DSV) of 200 mm. Median B0I distortions were 0.09 mm for the same DSV. For DSVs up to 500 mm, through-plane corrections are necessary to keep the median residual GNL distortion below 1 mm. 3D and 3D + corrections agreed within 0.15 mm. 2D-corrected images featured uncorrected through-plane distortions of up to 21.11 mm at a distance of 20-25 cm from the machine's isocenter. Based on the 4D-MRI patient scans, the average external body contour distortions were 3.1 mm (uncorrected) and 1.2 mm (2D-corrected), with maximum local distortions of 9.5 mm in the uncorrected images. No (residual) distortions were visible for the metastases, which were all located within 10 cm of the machine's isocenter. The interquartile range (IQR) of dose differences between planned and daily dose caused by variable patient setup, patient anatomy, and online plan adaptation was 1.37 Gy/Fx for the PTV D95%. When comparing dose on 3D-corrected with uncorrected (2D-corrected) images, the IQR was 0.61 (0.31) Gy/Fx. CONCLUSIONS: GNL is the main machine-related source of image distortions on the Unity MR-linac. For slice-based 4D-MRI, a full 3D correction can be applied after respiratory sorting to maximize spatial fidelity. The machine-specific 3D + correction did not substantially reduce residual geometric distortions compared to the machine-generic 3D correction for our MR-linac. In our patients, dosimetric variations in the target not related to geometric distortions were larger than those caused by geometric distortions.

Comparison of gamma- and DVH-based in vivo dosimetric plan evaluation for pelvic VMAT treatments.

BACKGROUND AND PURPOSE: To compare DVH-based quality assurance to a multi-parametric γ-based methodology for in vivo EPID dosimetry for VMAT to the pelvis. MATERIALS AND METHODS: For 47 rectum, 37 prostate, and 44 bladder VMAT treatments we reconstructed the 3D dose distributions of 387 fractions from in vivo EPID dosimetry. The difference between planned and measured dose was evaluated using γ analysis (3%/3mm) in the 50% isodose volume (IDV) and DVH differences (ΔD2, ΔD50 and ΔD98) of targets and organs at risk. The γ-indicators mean γ, γ pass rate and γ1% were compared to DVH-differences and their correlations were studied. DVH-based alerts on PTV and IDV were compared to γ-based alerts. RESULTS: Average PTV D50 and D98 dose differences were 0.0±2.2% (1SD) and -1.4±2.9% (1SD). Alert criteria of |ΔD50|<3.5-4.5% corresponded to an alert rate of about 10%. Strong correlations between mean γ and γ pass rate and difference in PTV ΔD50 were observed for all sites. DVH- and γ-based alerts agreed on >80% of the fractions for the majority of compared alert thresholds and methods. This agreement is >90% for the larger deviations. CONCLUSIONS: Strong correlations between some γ- and DVH indicators were found. Our comparison of multi-parametric alert strategies showed clinical equivalence for γ- and DVH-based methods.

Heart dose associated with overall survival in locally advanced NSCLC patients treated with hypofractionated chemoradiotherapy.

Association of heart dose and overall survival was investigated in a cohort including 469 locally-advanced NSCLC patients receiving daily low-dose hypofractionated chemo-radiotherapy. Significant associations were found over a range of dose parameters. Multivariate analysis showed significant associations of heart_V2Gy:HR=1.007%-1 (95% CI:1.002-1.013; p=0.006), age:HR=1.026year-1 (1.011-1.042; p=0.001) and GTV volume:HR=1.001cc-1 (1.000-1.002; p=0.006) with overall survival.

Dose-effect analysis of radiation induced rib fractures after thoracic SBRT.

BACKGROUND AND PURPOSE: To determine a dose-effect relation for radiation induced rib fractures after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC). Automatic rib delineation has enabled the analysis of a large patient group. MATERIAL AND METHODS: Four-hundred and sixty-six patients with stage I/II NSCLC received SBRT with a median of 54Gy in 3 fractions. The optimal EQD2-corrected dose parameter to predict (a)symptomatic fractures was found using Cox regression. Three normal tissue complication probability (NTCP) models based on this optimal parameter were constructed: (1) at a median follow up (FU) of 26months, (2) for all data, with time to toxicity taken into account and (3) at a FU of 26months, excluding low dose ribs. RESULTS: The median time to fracture was 22 (range 5-51) months. Maximum rib dose best predicted fractures. The TD50 (dose with 50% complication) of the second NTCP model was 375Gy. The TD50 was significantly higher for the other models indicating an under-estimation of the dose effect at the median follow-up time and/or when excluding low dose ribs. CONCLUSIONS: The risk of symptomatic rib fractures after SBRT was significantly correlated to dose, and was <5% at 26months when Dmax<225Gy.