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Background: Real‐time tumor tracking is one motion management method to address motion‐induced uncertainty. To date, fiducial markers are often required to reliably track lung tumors with X‐ray imaging, which carries risks of complications and leads to prolonged treatment time. A markerless tracking approach is thus desirable. Deep learning‐based approaches have shown promise for markerless tracking, but systematic evaluation and procedures to investigate applicability in individual cases are missing. Moreover, few efforts have been made to provide bounding box prediction and mask segmentation simultaneously, which could allow either rigid or deformable multi‐leaf collimator tracking. Purpose: The purpose of this study was to implement a deep learning‐based markerless lung tumor tracking model exploiting patient‐specific training which outputs both a bounding box and a mask segmentation simultaneously. We also aimed to compare the two kinds of predictions and to implement a specific procedure to understand the feasibility of markerless tracking on individual cases. Methods: We first trained a Retina U‐Net baseline model on digitally reconstructed radiographs (DRRs) generated from a public dataset containing 875 CT scans and corresponding lung nodule annotations. Afterwards, we used an independent cohort of 97 lung patients to develop a patient‐specific refinement procedure. In order to determine the optimal hyperparameters for automatic patient‐specific training, we selected 13 patients for validation where the baseline model predicted a bounding box on planning CT (PCT)‐DRR with intersection over union (IoU) with the ground‐truth higher than 0.7. The final test set contained the remaining 84 patients with varying PCT‐DRR IoU. For each testing patient, the baseline model was refined on the PCT‐DRR to generate a patient‐specific model, which was then tested on a separate 10‐phase 4DCT‐DRR to mimic the intrafraction motion during treatment. A template matching algorithm served as benchmark model. The testing results were evaluated by four metrics: the center of mass (COM) error and the Dice similarity coefficient (DSC) for segmentation masks, and the center of box (COB) error and the DSC for bounding box detections. Performance was compared to the benchmark model including statistical testing for significance. Results: A PCT‐DRR IoU value of 0.2 was shown to be the threshold dividing inconsistent (68%) and consistent (100%) success (defined as mean bounding box DSC > 0.6) of PS models on 4DCT‐DRRs. Thirty‐seven out of the eighty‐four testing cases had a PCT‐DRR IoU above 0.2. For these 37 cases, the mean COM error was 2.6 mm, the mean segmentation DSC was 0.78, the mean COB error was 2.7 mm, and the mean box DSC was 0.83. Including the validation cases, the model was applicable to 50 out of 97 patients when using the PCT‐DRR IoU threshold of 0.2. The inference time per frame was 170 ms. The model outperformed the benchmark model on all metrics, and the comparison was significant (p < 0.001) over the 37 PCT‐DRR IoU > 0.2 cases, but not over the undifferentiated 84 testing cases. Conclusions: The implemented patient‐specific refinement approach based on a pre‐trained baseline model was shown to be applicable to markerless tumor tracking in simulated radiographs for lung cases. [ABSTRACT FROM AUTHOR]

Children, including those who are deaf, become aware of and learn about their environments through playing and social and cultural interactions. For most deaf children, preschool classrooms are optimal spaces for these interactions to occur, but only if they can fully engage with this environment. We discuss the need for and constituent aspects of full access to learning in these environments for deaf children. Vygotsky's sociocultural theory is employed chiefly as the basis for exploring and analyzing useful strategies for educators and families of deaf children. Our analysis focuses on processes in which individuals create knowledge through interacting with other people and the environment, a core emphasis of our work. We also discuss that, concomitant with full access to linguistic and social opportunities, deaf preschoolers develop a stronger sense of self, which leads to the development of cultures and languages in and out of their families. [ABSTRACT FROM AUTHOR]

Purpose: The implementation of volumetric in‐room imaging for online adaptive radiotherapy makes extensive testing of this image data for treatment planning necessary. Especially for proton beams the higher sensitivity to stopping power properties of the tissue results in more stringent requirements. Current approaches mainly focus on recalculation of the plans on the new image data, lacking experimental verification, and ignoring the impact on the plan re‐optimization process. The aim of this study was to use gel and film dosimetry coupled with a three‐dimensional (3D) printed head phantom (based on the planning CT of the patient) for 3D range verification of intensity‐corrected cone beam computed tomography (CBCT) image data for adaptive proton therapy. Methods: Single field uniform dose pencil beam scanning proton plans were optimized for three different patients on the patients' planning CT (planCT) and the patients' intensity‐corrected CBCT (scCBCT) for the same target volume using the same optimization constraints. The CBCTs were corrected on projection level using the planCT as a prior. The dose optimized on planCT and recalculated on scCBCT was compared in terms of proton range differences (80% distal fall‐off, recalculation). Moreover, the dose distribution resulting from recalculation of the scCBCT‐optimized plan on the planCT and the original planCT dose distribution were compared (simulation). Finally, the two plans of each patient were irradiated on the corresponding patient‐specific 3D printed head phantom using gel dosimetry inserts for one patient and film dosimetry for all three patients. Range differences were extracted from the measured dose distributions. The measured and the simulated range differences were corrected for range differences originating from the initial plans and evaluated. Results: The simulation approach showed high agreement with the standard recalculation approach. The median values of the range differences of these two methods agreed within 0.1 mm and the interquartile ranges (IQRs) within 0.3 mm for all three patients. The range differences of the film measurement were accurately matching with the simulation approach in the film plane. The median values of these range differences deviated less than 0.1 mm and the IQRs less than 0.4 mm. For the full 3D evaluation of the gel range differences, the median value and IQR matched those of the simulation approach within 0.7 and 0.5 mm, respectively. scCBCT‐ and planCT‐based dose distributions were found to have a range agreement better than 3 mm (median and IQR) for all considered scenarios (recalculation, simulation, and measurement). Conclusions: The results of this initial study indicate that an online adaptive proton workflow based on scatter‐corrected CBCT image data for head irradiations is feasible. The novel presented measurement‐ and simulation‐based method was shown to be equivalent to the standard literature recalculation approach. Additionally, it has the capability to catch effects of image differences on the treatment plan optimization. This makes the measurement‐based approach particularly interesting for quality assurance of CBCT‐based online adaptive proton therapy. The observed uncertainties could be kept within those of the registration and positioning. The proposed validation could also be applied for other alternative in‐room images, e.g. for MR‐based pseudoCTs. [ABSTRACT FROM AUTHOR]

Background: Longitudinal assessments of apparent diffusion coefficients (ADCs) derived from diffusion-weighted imaging (DWI) during intracranial radiotherapy at magnetic resonance imaging-guided linear accelerators (MR-linacs) could enable early response assessment by tracking tumor diffusivity changes. However, DWI pulse sequences are currently unavailable in clinical practice at low-field MR-linacs. Quantifying the in vivo repeatability of ADC measurements is a crucial step towards clinical implementation of DWI sequences but has not yet been reported on for low-field MR-linacs. This study assessed ADC measurement repeatability in a phantom and in vivo at a 0.35 T MR-linac. Methods: Eleven volunteers and a diffusion phantom were imaged on a 0.35 T MR-linac. Two echo-planar imaging DWI sequence variants, emphasizing high spatial resolution ("highRes") and signal-to-noise ratio ("highSNR"), were investigated. A test–retest study with an intermediate outside-scanner-break was performed to assess repeatability in the phantom and volunteers' brains. Mean ADCs within phantom vials, cerebrospinal fluid (CSF), and four brain tissue regions were compared to literature values. Absolute relative differences of mean ADCs in pre- and post-break scans were calculated for the diffusion phantom, and repeatability coefficients (RC) and relative RC (relRC) with 95% confidence intervals were determined for each region-of-interest (ROI) in volunteers. Results: Both DWI sequence variants demonstrated high repeatability, with absolute relative deviations below 1% for water, dimethyl sulfoxide, and polyethylene glycol in the diffusion phantom. RelRCs were 7% [5%, 12%] (CSF; highRes), 12% [9%, 22%] (CSF; highSNR), 9% [8%, 12%] (brain tissue ROIs; highRes), and 6% [5%, 7%] (brain tissue ROIs; highSNR), respectively. ADCs measured with the highSNR variant were consistent with literature values for volunteers, while smaller mean values were measured for the diffusion phantom. Conversely, the highRes variant underestimated ADCs compared to literature values, indicating systematic deviations. Conclusions: High repeatability of ADC measurements in a diffusion phantom and volunteers' brains were measured at a low-field MR-linac. The highSNR variant outperformed the highRes variant in accuracy and repeatability, at the expense of an approximately doubled voxel volume. The observed high in vivo repeatability confirms the potential utility of DWI at low-field MR-linacs for early treatment response assessment. [ABSTRACT FROM AUTHOR]

Background: Cone beam computed tomography (CBCT) is widely used in many medical fields. However, conventional CBCT circular scans suffer from cone beam (CB) artifacts that limit the quality and reliability of the reconstructed images due to incomplete data. Purpose: Saddle trajectories in theory might be able to improve the CBCT image quality by providing a larger region with complete data. Therefore, we investigated the feasibility and performance of saddle trajectory CBCT scans and compared them to circular trajectory scans. Methods: We performed circular and saddle trajectory scans using a novel robotic CBCT scanner (Mobile ImagingRing (IRm); medPhoton, Salzburg, Austria). For the saddle trajectory, the gantry executed yaw motion up to ±10∘$\pm 10^{\circ }$ using motorized wheels driving on the floor. An infrared (IR) tracking device with reflective markers was used for online geometric calibration correction (mainly floor unevenness). All images were reconstructed using penalized least‐squares minimization with the conjugate gradient algorithm from RTK with 0.5×0.5×0.5mm3$0.5 \times 0.5\times 0.5 \text{ mm}^3$ voxel size. A disk phantom and an Alderson phantom were scanned to assess the image quality. Results were correlated with the local incompleteness value represented by tan(ψ)$\tan (\psi)$, which was calculated at each voxel as a function of the source trajectory and the voxel's 3D coordinates. We assessed the magnitude of CB artifacts using the full width half maximum (FWHM) of each disk profile in the axial center of the reconstructed images. Spatial resolution was also quantified by the modulation transfer function at 10% (MTF10). Results: When using the saddle trajectory, the region without CB artifacts was increased from 43 to 190 mm in the SI direction compared to the circular trajectory. This region coincided with low values for tan(ψ)$\tan (\psi)$. When tan(ψ)$\tan (\psi)$ was larger than 0.02, we found there was a linear relationship between the FWHM and tan(ψ)$\tan (\psi)$. For the saddle, IR tracking allowed the increase of MTF10 from 0.37 to 0.98 lp/mm. Conclusions: We achieved saddle trajectory CBCT scans with a novel CBCT system combined with IR tracking. The results show that the saddle trajectory provides a larger region with reliable reconstruction compared to the circular trajectory. The proposed method can be used to evaluate other non‐circular trajectories. [ABSTRACT FROM AUTHOR]

Background: Current commercially available hybrid magnetic resonance linear accelerators (MR‐Linac) use 2D+t cine MR imaging to provide intra‐fractional motion monitoring. However, given the limited temporal resolution of cine MR imaging, target intra‐frame motion deterioration effects, resulting in effective time latency and motion artifacts in the image domain, can be appreciable, especially in the case of fast breathing. Purpose: The aim of this work is to investigate intra‐frame motion deterioration effects in MR‐guided radiotherapy (MRgRT) by simulating the motion‐corrupted image acquisition, and to explore the feasibility of deep‐learning‐based compensation approaches, relying on the intra‐frame motion information which is spatially and temporally encoded in the raw data (k‐space). Methods: An intra‐frame motion model was defined to simulate motion‐corrupted MR images, with 4D anthropomorphic digital phantoms being exploited to provide ground truth 2D+t cine MR sequences. A total number of 10 digital phantoms were generated for lung cancer patients, with randomly selected eight patients for training or validation and the remaining two for testing. The simulation code served as the data generator, and a dedicated motion pattern perturbation scheme was proposed to build the intra‐frame motion database, where three degrees of freedom were designed to guarantee the diversity of intra‐frame motion trajectories, enabling a thorough exploration in the domain of the potential anatomical structure positions. U‐Nets with three types of loss functions: L1 or L2 loss defined in image or Fourier domain, referred to as NNImgLoss‐L1, NNFloss‐L1 and NNL2‐Loss were trained to extract information from the motion‐corrupted image and used to estimate the ground truth final‐position image, corresponding to the end of the acquisition. Images before and after compensation were evaluated in terms of (i) image mean‐squared error (MSE) and mean absolute error (MAE), and (ii) accuracy of gross tumor volume (GTV) contouring, based on optical‐flow image registration. Results: Image degradation caused by intra‐frame motion was observed: for a linearly and fully acquired Cartesian readout k‐space trajectory, intra‐frame motion resulted in an imaging latency of approximately 50% of the acquisition time; in comparison, the motion artifacts exhibited only a negligible contribution to the overall geometric errors. All three compensation models led to a decrease in image MSE/MAE and GTV position offset compared to the motion‐corrupted image. In the investigated testing dataset for GTV contouring, the average dice similarity coefficients (DSC) improved from 88% to 96%, and the 95th percentile Hausdorff distance (HD95) dropped from 4.8 mm to 2.1 mm. Different models showed slight performance variations across different intra‐frame motion amplitude categories: NNImgLoss‐L1 excelled for small/medium amplitudes, whereas NNFloss‐L1 demonstrated higher DSC median values at larger amplitudes. The saliency maps of the motion‐corrupted image highlighted the major contribution of the later acquired k‐space data, as well as the edges of the moving anatomical structures at their final positions, during the model inference stage. Conclusions: Our results demonstrate the deep‐learning‐based approaches have the potential to compensate for intra‐frame motion by utilizing the later acquired data to drive the convergence of the earlier acquired k‐space components. [ABSTRACT FROM AUTHOR]

Objectives: Deep learning-based auto-segmentation of head and neck cancer (HNC) tumors is expected to have better reproducibility than manual delineation. Positron emission tomography (PET) and computed tomography (CT) are commonly used in tumor segmentation. However, current methods still face challenges in handling whole-body scans where a manual selection of a bounding box may be required. Moreover, different institutions might still apply different guidelines for tumor delineation. This study aimed at exploring the auto-localization and segmentation of HNC tumors from entire PET/CT scans and investigating the transferability of trained baseline models to external real world cohorts. Methods: We employed 2D Retina Unet to find HNC tumors from whole-body PET/CT and utilized a regular Unet to segment the union of the tumor and involved lymph nodes. In comparison, 2D/3D Retina Unets were also implemented to localize and segment the same target in an end-to-end manner. The segmentation performance was evaluated via Dice similarity coefficient (DSC) and Hausdorff distance 95th percentile (HD95). Delineated PET/CT scans from the HECKTOR challenge were used to train the baseline models by 5-fold cross-validation. Another 271 delineated PET/CTs from three different institutions (MAASTRO, CRO, BERLIN) were used for external testing. Finally, facility-specific transfer learning was applied to investigate the improvement of segmentation performance against baseline models. Results: Encouraging localization results were observed, achieving a maximum omnidirectional tumor center difference lower than 6.8 cm for external testing. The three baseline models yielded similar averaged cross-validation (CV) results with a DSC in a range of 0.71–0.75, while the averaged CV HD95 was 8.6, 10.7 and 9.8 mm for the regular Unet, 2D and 3D Retina Unets, respectively. More than a 10% drop in DSC and a 40% increase in HD95 were observed if the baseline models were tested on the three external cohorts directly. After the facility-specific training, an improvement in external testing was observed for all models. The regular Unet had the best DSC (0.70) for the MAASTRO cohort, and the best HD95 (7.8 and 7.9 mm) in the MAASTRO and CRO cohorts. The 2D Retina Unet had the best DSC (0.76 and 0.67) for the CRO and BERLIN cohorts, and the best HD95 (12.4 mm) for the BERLIN cohort. Conclusion: The regular Unet outperformed the other two baseline models in CV and most external testing cohorts. Facility-specific transfer learning can potentially improve HNC segmentation performance for individual institutions, where the 2D Retina Unets could achieve comparable or even better results than the regular Unet. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI)‐guided radiotherapy with multileaf collimator (MLC)‐tracking is a promising technique for intra‐fractional motion management, achieving high dose conformality without prolonging treatment times. To improve beam‐target alignment, the geometric error due to system latency should be reduced by using temporal prediction. Purpose: To experimentally compare linear regression (LR) and long‐short‐term memory (LSTM) motion prediction models for MLC‐tracking on an MRI‐linac using multiple patient‐derived traces with different complexities. Methods: Experiments were performed on a prototype 1.0 T MRI‐linac capable of MLC‐tracking. A motion phantom was programmed to move a target in superior‐inferior (SI) direction according to eight lung cancer patient respiratory motion traces. Target centroid positions were localized from sagittal 2D cine MRIs acquired at 4 Hz using a template matching algorithm. The centroid positions were input to one of four motion prediction models. We used (1) a LSTM network which had been optimized in a previous study on patient data from another cohort (offline LSTM). We also used (2) the same LSTM model as a starting point for continuous re‐optimization of its weights during the experiment based on recent motion (offline+online LSTM). Furthermore, we implemented (3) a continuously updated LR model, which was solely based on recent motion (online LR). Finally, we used (4) the last available target centroid without any changes as a baseline (no‐predictor). The predictions of the models were used to shift the MLC aperture in real‐time. An electronic portal imaging device (EPID) was used to visualize the target and MLC aperture during the experiments. Based on the EPID frames, the root‐mean‐square error (RMSE) between the target and the MLC aperture positions was used to assess the performance of the different motion predictors. Each combination of motion trace and prediction model was repeated twice to test stability, for a total of 64 experiments. Results: The end‐to‐end latency of the system was measured to be (389 ± 15) ms and was successfully mitigated by both LR and LSTM models. The offline+online LSTM was found to outperform the other models for all investigated motion traces. It obtained a median RMSE over all traces of (2.8 ± 1.3) mm, compared to the (3.2 ± 1.9) mm of the offline LSTM, the (3.3 ± 1.4) mm of the online LR and the (4.4 ± 2.4) mm when using the no‐predictor. According to statistical tests, differences were significant (p‐value <0.05) among all models in a pair‐wise comparison, but for the offline LSTM and online LR pair. The offline+online LSTM was found to be more reproducible than the offline LSTM and the online LR with a maximum deviation in RMSE between two measurements of 10%. Conclusions: This study represents the first experimental comparison of different prediction models for MRI‐guided MLC‐tracking using several patient‐derived respiratory motion traces. We have shown that among the investigated models, continuously re‐optimized LSTM networks are the most promising to account for the end‐to‐end system latency in MRI‐guided radiotherapy with MLC‐tracking. [ABSTRACT FROM AUTHOR]

Background and purpose: Magnetic resonance imaging guided radiotherapy (MRgRT) offers treatment plan adaptation to the anatomy of the day. In the current MRgRT workflow, this requires the time consuming and repetitive task of manual delineation of organs-at-risk (OARs), which is also prone to inter- and intra-observer variability. Therefore, deep learning autosegmentation (DLAS) is becoming increasingly attractive. No investigation of its application to OARs in thoracic magnetic resonance images (MRIs) from MRgRT has been done so far. This study aimed to fill this gap. Materials and methods: 122 planning MRIs from patients treated at a 0.35 T MR-Linac were retrospectively collected. Using an 80/19/23 (training/validation/test) split, individual 3D U-Nets for segmentation of the left lung, right lung, heart, aorta, spinal canal and esophagus were trained. These were compared to the clinically used contours based on Dice similarity coefficient (DSC) and Hausdorff distance (HD). They were also graded on their clinical usability by a radiation oncologist. Results: Median DSC was 0.96, 0.96, 0.94, 0.90, 0.88 and 0.78 for left lung, right lung, heart, aorta, spinal canal and esophagus, respectively. Median 95th percentile values of the HD were 3.9, 5.3, 5.8, 3.0, 2.6 and 3.5 mm, respectively. The physician preferred the network generated contours over the clinical contours, deeming 85 out of 129 to not require any correction, 25 immediately usable for treatment planning, 15 requiring minor and 4 requiring major corrections. Conclusions: We trained 3D U-Nets on clinical MRI planning data which produced accurate delineations in the thoracic region. DLAS contours were preferred over the clinical contours. [ABSTRACT FROM AUTHOR]

Background: The treatment of moving tumor entities is expected to have superior clinical outcomes, using image‐guided adaptive intensity‐modulated proton therapy (IMPT). Purpose: For 21 lung cancer patients, IMPT dose calculations were performed on scatter‐corrected 4D cone beam CTs (4DCBCTcor) to evaluate their potential for triggering treatment adaptation. Additional dose calculations were performed on corresponding planning 4DCTs and day‐of‐treatment 4D virtual CTs (4DvCTs). Methods: A 4DCBCT correction workflow, previously validated on a phantom, generates 4DvCT (CT‐to‐CBCT deformable registration) and 4DCBCTcor images (projection‐based correction using 4DvCT as a prior) with 10 phase bins, using day‐of‐treatment free‐breathing CBCT projections and planning 4DCT images as input. Using a research planning system, robust IMPT plans administering eight fractions of 7.5 Gy were created on a free‐breathing planning CT (pCT) contoured by a physician. The internal target volume (ITV) was overridden with muscle tissue. Robustness settings for range and setup uncertainties were 3% and 6 mm, and a Monte Carlo dose engine was used. On every phase of planning 4DCT, day‐of‐treatment 4DvCT, and 4DCBCTcor, the dose was recalculated. For evaluation, image analysis as well as dose analysis were performed using mean error (ME) and mean absolute error (MAE) analysis, dose–volume histogram (DVH) parameters, and 2%/2‐mm gamma pass rate analysis. Action levels (1.6% ITV D98 and 90% gamma pass rate) based on our previous phantom validation study were set to determine which patients had a loss of dosimetric coverage. Results: Quality enhancements of 4DvCT and 4DCBCTcor over 4DCBCT were observed. ITV D98% and bronchi D2% had its largest agreement for 4DCBCTcor–4DvCT, and the largest gamma pass rates (>94%, median 98%) were found for 4DCBCTcor–4DvCT. Deviations were larger and gamma pass rates were smaller for 4DvCT–4DCT and 4DCBCTcor–4DCT. For five patients, deviations were larger than the action levels, suggesting substantial anatomical changes between pCT and CBCT projections acquisition. Conclusions: This retrospective study shows the feasibility of daily proton dose calculation on 4DCBCTcor for lung tumor patients. The applied method is of clinical interest as it generates up‐to‐date in‐room images, accounting for breathing motion and anatomical changes. This information could be used to trigger replanning. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state‐of‐the‐art treatment techniques, such as MR‐guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. Purpose: We conducted a comparison of accumulated doses for MRgRT, robustly optimized non‐adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high‐grade toxicities. Methods: Data of 18 early‐stage central lung tumor patients, treated at a 0.35 T MR‐linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non‐adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose‐volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs‐at‐risk (OARs) within 2 cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed‐rank tests between S1 & S2, and S1 & S3. Results: The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: –8%; S3: –23%) and mean heart dose (S2: –79%; S3: –83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1–2 cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantly different for OARs within 1 cm of the PTV. Conclusions: A significant dose sparing potential of non‐adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near‐maximum dose to the bronchial tree was not significantly different for MRgRT and non‐adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT. [ABSTRACT FROM AUTHOR]

Background: Hybrid devices that combine radiation therapy and MR-imaging have been introduced in the clinical routine for the treatment of lung cancer. This opened up not only possibilities in terms of accurate tumor tracking, dose delivery and adapted treatment planning, but also functional lung imaging. The aim of this study was to show the feasibility of Non-uniform Fourier Decomposition (NuFD) MRI at a 0.35 T MR-Linac as a potential treatment response assessment tool, and propose two signal normalization strategies for enhancing the reproducibility of the results. Methods: Ten healthy volunteers (median age 28 ± 8 years, five female, five male) were repeatedly scanned at a 0.35 T MR-Linac using an optimized 2D+t balanced steady-state free precession (bSSFP) sequence for two coronal slice positions. Image series were acquired in normal free breathing with breaks inside and outside the scanner as well as deep and shallow breathing. Ventilation- and perfusion-weighted maps were generated for each image series using NuFD. For intra-volunteer ventilation map reproducibility, a normalization factor was defined based on the linear correlation of the ventilation signal and diaphragm position of each scan as well as the diaphragm motion amplitude of a reference scan. This allowed for the correction of signal dependency on the diaphragm motion amplitude, which varies with breathing patterns. The second strategy, which can be used for ventilation and perfusion, eliminates the dependency on the signal amplitude by normalizing the ventilation/perfusion maps with the average ventilation/perfusion signal within a selected region-of-interest (ROI). The position and size dependency of this ROI was analyzed. To evaluate the performance of both approaches, the normalized ventilation/perfusion-weighted maps were compared and the deviation of the mean ventilation/perfusion signal from the reference was calculated for each scan. Wilcoxon signed-rank tests were performed to test whether the normalization methods can significantly improve the reproducibility of the ventilation/perfusion maps. Results: The ventilation- and perfusion-weighted maps generated with the NuFD algorithm demonstrated a mostly homogenous distribution of signal intensity as expected for healthy volunteers regardless of the breathing maneuver and slice position. Evaluation of the ROI's size and position dependency showed small differences in the performance. Applying both normalization strategies improved the reproducibility of the ventilation by reducing the median deviation of all scans to 9.1%, 5.7% and 8.6% for the diaphragm-based, the best and worst performing ROI-based normalization, respectively, compared to 29.5% for the non-normalized scans. The significance of this improvement was confirmed by the Wilcoxon signed rank test with p < 0.01 at α = 0.05 . A comparison of the techniques against each other revealed a significant difference in the performance between best ROI-based normalization and worst ROI ( p = 0.01 ) and between best ROI-based normalization and scaling factor ( p = 0.02 ), but not between scaling factor and worst ROI ( p = 0.71 ). Using the ROI-based approach for the perfusion-maps, the uncorrected deviation of 10.2% was reduced to 5.3%, which was shown to be significant ( p < 0.01 ). Conclusions: Using NuFD for non-contrast enhanced functional lung MRI at a 0.35 T MR-Linac is feasible and produces plausible ventilation- and perfusion-weighted maps for volunteers without history of chronic pulmonary diseases utilizing different breathing patterns. The reproducibility of the results in repeated scans significantly benefits from the introduction of the two normalization strategies, making NuFD a potential candidate for fast and robust early treatment response assessment of lung cancer patients during MR-guided radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Online adaptive radiation therapy (RT) using hybrid magnetic resonance linear accelerators (MR-Linacs) can administer a tailored radiation dose at each treatment fraction. Daily MR imaging followed by organ and target segmentation adjustments allow to capture anatomical changes, improve target volume coverage, and reduce the risk of side effects. The introduction of automatic segmentation techniques could help to further improve the online adaptive workflow by shortening the re-contouring time and reducing intra- and inter-observer variability. In fractionated RT, prior knowledge, such as planning images and manual expert contours, is usually available before irradiation, but not used by current artificial intelligence-based autocontouring approaches. Purpose: The goal of this study was to train convolutional neural networks (CNNs) for automatic segmentation of bladder, rectum (organs at risk, OARs), and clinical target volume (CTV) for prostate cancer patients treated at 0.35 T MR-Linacs. Furthermore, we tested the CNNs generalization on data from independent facilities and compared them with the MR-Linac treatment planning system (TPS) propagated structures currently used in clinics. Finally, expert planning delineations were utilized for patient- (PS) and facility-specific (FS) transfer learning to improve auto-segmentation of CTV and OARs on fraction images. Methods: In this study, data from fractionated treatments at 0.35 T MR-Linacs were leveraged to develop a 3D U-Net-based automatic segmentation. Cohort C1 had 73 planning images and cohort C2 had 19 planning and 240 fraction images. The baseline models (BMs) were trained solely on C1 planning data using 53 MRIs for training and 10 for validation. To assess their accuracy, the models were tested on three data subsets: (i) 10 C1 planning images not used for training, (ii) 19 C2 planning,and (iii) 240 C2 fraction images.BMs also served as a starting point for FS and PS transfer learning, where the planning images from C2 were used for network parameter fine tuning.The segmentation output of the different trained models was compared against expert ground truth by means of geometric metrics.Moreover, a trained physician graded the network segmentations as well as the segmentations propagated by the clinical TPS. Results: The BMs showed dice similarity coefficients (DSC) of 0.88(4) and 0.93(3) for the rectum and the bladder, respectively, independent of the facility. CTV segmentation with the BM was the best for intermediate- and high-risk cancer patients from C1 with DSC=0.84(5) and worst for C2 with DSC=0.74(7). The PS transfer learning brought a significant improvement in the CTV segmentation, yielding DSC=0.72(4) for post-prostatectomy and low-risk patients and DSC=0.88(5) for intermediate- and high-risk patients. The FS training did not improve the segmentation accuracy considerably. The physician’s assessment of the TPS-propagated versus network-generated structures showed a clear advantage of the latter. Conclusions: The obtained results showed that the presented segmentation technique has potential to improve automatic segmentation for MR-guided RT. [ABSTRACT FROM AUTHOR]

Background: Hybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.Methods: Fifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.Results: All subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.Conclusion: With online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes. [ABSTRACT FROM AUTHOR]

Background: The evaluation of automatic segmentation algorithms is commonly performed using geometric metrics. An analysis based on dosimetric parameters might be more relevant in clinical practice but is often lacking in the literature. The aim of this study was to investigate the impact of state-of-the-art 3D U-Net-generated organ delineations on dose optimization in radiation therapy (RT) for prostate cancer patients.Methods: A database of 69 computed tomography images with prostate, bladder, and rectum delineations was used for single-label 3D U-Net training with dice similarity coefficient (DSC)-based loss. Volumetric modulated arc therapy (VMAT) plans have been generated for both manual and automatic segmentations with the same optimization settings. These were chosen to give consistent plans when applying perturbations to the manual segmentations. Contours were evaluated in terms of DSC, average and 95% Hausdorff distance (HD). Dose distributions were evaluated with the manual segmentation as reference using dose volume histogram (DVH) parameters and a 3%/3 mm gamma-criterion with 10% dose cut-off. A Pearson correlation coefficient between DSC and dosimetric metrics, i.e. gamma index and DVH parameters, has been calculated.Results: 3D U-Net-based segmentation achieved a DSC of 0.87 (0.03) for prostate, 0.97 (0.01) for bladder and 0.89 (0.04) for rectum. The mean and 95% HD were below 1.6 (0.4) and below 5 (4) mm, respectively. The DVH parameters, V[Formula: see text] for the bladder and V[Formula: see text] for the rectum, showed agreement between dose distributions within [Formula: see text] and [Formula: see text], respectively. The D[Formula: see text] and V[Formula: see text], for prostate and its 3 mm expansion (surrogate clinical target volume) showed agreement with the reference dose distribution within 2% and 3 Gy with the exception of one case. The average gamma pass-rate was 85%. The comparison between geometric and dosimetric metrics showed no strong statistically significant correlation.Conclusions: The 3D U-Net developed for this work achieved state-of-the-art geometrical performance. Analysis based on clinically relevant DVH parameters of VMAT plans demonstrated neither excessive dose increase to OARs nor substantial under/over-dosage of the target in all but one case. Yet the gamma analysis indicated several cases with low pass rates. The study highlighted the importance of adding dosimetric analysis to the standard geometric evaluation. [ABSTRACT FROM AUTHOR]

Proton therapy treatment for lungs remains challenging as images enabling the detection of inter- and intra-fractional motion, which could be used for proton dose adaptation, are not readily available. 4D computed tomography (4DCT) provides high image quality but is rarely available in-room, while in-room 4D cone beam computed tomography (4DCBCT) suffers from image quality limitations stemming mostly from scatter detection. This study investigated the feasibility of using virtual 4D computed tomography (4DvCT) as a prior for a phase-per-phase scatter correction algorithm yielding a 4D scatter corrected cone beam computed tomography image (4DCBCTcor), which can be used for proton dose calculation. 4DCT and 4DCBCT scans of a porcine lung phantom, which generated reproducible ventilation, were acquired with matching breathing patterns. Diffeomorphic Morphons, a deformable image registration algorithm, was used to register the mid-position 4DCT to the mid-position 4DCBCT and yield a 4DvCT. The 4DCBCT was reconstructed using motion-aware reconstruction based on spatial and temporal regularization (MA-ROOSTER). Successively for each phase, digitally reconstructed radiographs of the 4DvCT, simulated without scatter, were exploited to correct scatter in the corresponding CBCT projections. The 4DCBCTcor was then reconstructed with MA-ROOSTER using the corrected CBCT projections and the same settings and deformation vector fields as those already used for reconstructing the 4DCBCT. The 4DCBCTcor and the 4DvCT were evaluated phase-by-phase, performing proton dose calculations and comparison to those of a ground truth 4DCT by means of dose-volume-histograms (DVH) and gamma pass-rates (PR). For accumulated doses, DVH parameters deviated by at most 1.7% in the 4DvCT and 2.0% in the 4DCBCTcor case. The gamma PR for a (2%, 2 mm) criterion with 10% threshold were at least 93.2% (4DvCT) and 94.2% (4DCBCTcor), respectively. The 4DCBCTcor technique enabled accurate proton dose calculation, which indicates the potential for applicability to clinical 4DCBCT scans. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.Materials and Methods: 20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.Results: The dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.Conclusions: A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected. [ABSTRACT FROM AUTHOR]

• Description of intra-fractional motion management workflow in MRI-guided radiotherapy. • Envisioned workflow with both highest dosimetric accuracy and duty cycle efficiency. • Focus on real-time implementation based on artificial intelligence. MRI-guided radiotherapy (MRIgRT) is a highly complex treatment modality, allowing adaptation to anatomical changes occurring from one treatment day to the other (inter-fractional), but also to motion occurring during a treatment fraction (intra-fractional). In this vision paper, we describe the different steps of intra-fractional motion management during MRIgRT, from imaging to beam adaptation, and the solutions currently available both clinically and at a research level. Furthermore, considering the latest developments in the literature, a workflow is foreseen in which motion-induced over- and/or under-dosage is compensated in 3D, with minimal impact to the radiotherapy treatment time. Considering the time constraints of real-time adaptation, a particular focus is put on artificial intelligence (AI) solutions as a fast and accurate alternative to conventional algorithms. [ABSTRACT FROM AUTHOR]

• Comparison of three AI algorithms for real-time prediction of future tumor contours. • Usage of clinical cine MRI data from low-field MR-linacs from two institutions. • Prediction times compatible with reported MLC-tracking latencies on MR-linacs. Magnetic resonance imaging guided radiotherapy (MRgRT) with deformable multileaf collimator (MLC) tracking would allow to tackle both rigid displacement and tumor deformation without prolonging treatment. However, the system latency must be accounted for by predicting future tumor contours in real-time. We compared the performance of three artificial intelligence (AI) algorithms based on long short-term memory (LSTM) modules for the prediction of 2D-contours 500 ms into the future. Models were trained (52 patients, 3.1 h of motion), validated (18 patients, 0.6 h) and tested (18 patients, 1.1 h) with cine MRs from patients treated at one institution. Additionally, we used three patients (2.9 h) treated at another institution as second testing set. We implemented 1) a classical LSTM network (LSTM-shift) predicting tumor centroid positions in superior-inferior and anterior-posterior direction which are used to shift the last observed tumor contour. The LSTM-shift model was optimized both in an offline and online fashion. We also implemented 2) a convolutional LSTM model (ConvLSTM) to directly predict future tumor contours and 3) a convolutional LSTM combined with spatial transformer layers (ConvLSTM-STL) to predict displacement fields used to warp the last tumor contour. The online LSTM-shift model was found to perform slightly better than the offline LSTM-shift and significantly better than the ConvLSTM and ConvLSTM-STL. It achieved a 50% Hausdorff distance of 1.2 mm and 1.0 mm for the two testing sets, respectively. Larger motion ranges were found to lead to more substantial performance differences across the models. LSTM networks predicting future centroids and shifting the last tumor contour are the most suitable for tumor contour prediction. The obtained accuracy would allow to reduce residual tracking errors during MRgRT with deformable MLC-tracking. [ABSTRACT FROM AUTHOR]

• Deep learning PET and CT-based DM and OS time-to-event models showed predictive capability. • PET-only achieved the best prognosis performance. • Unlike CT, GTV segmentation is not necessary for PET-based prognosis. Recent studies have shown that deep learning based on pre-treatment positron emission tomography (PET) or computed tomography (CT) is promising for distant metastasis (DM) and overall survival (OS) prognosis in head and neck cancer (HNC). However, lesion segmentation is typically required, resulting in a predictive power susceptible to variations in primary and lymph node gross tumor volume (GTV) segmentation. This study aimed at achieving prognosis without GTV segmentation, and extending single modality prognosis to joint PET/CT to allow investigating the predictive performance of combined- compared to single-modality inputs. We employed a 3D-Resnet combined with a time-to-event outcome model to incorporate censoring information. We focused on the prognosis of DM and OS for HNC patients. For each clinical endpoint, five models with PET and/or CT images as input were compared: PET-GTV, PET-only, CT-GTV, CT-only, and PET/CT-GTV models, where -GTV indicates that the corresponding images were masked using the GTV contour. Publicly available delineated CT and PET scans from 4 different Canadian hospitals (293) and the MAASTRO clinic (74) were used for training by 3-fold cross-validation (CV). For independent testing, we used 110 patients from a collaborating institution. The predictive performance was evaluated via Harrell's Concordance Index (HCI) and Kaplan-Meier curves. In a 5-year time-to-event analysis, all models could produce CV HCIs with median values around 0.8 for DM and 0.7 for OS. The best performance was obtained with the PET-only model, achieving a median testing HCI of 0.82 for DM and 0.69 for OS. Compared with the PET/CT-GTV model, the PET-only still had advantages of up to 0.07 in terms of testing HCI. The Kaplan-Meier curves and corresponding log-rank test results also demonstrated significant stratification capability of our models for the testing cohort. Deep learning-based DM and OS time-to-event models showed predictive capability and could provide indications for personalized RT. The best predictive performance achieved by the PET-only model suggested GTV segmentation might be less relevant for PET-based prognosis. [ABSTRACT FROM AUTHOR]

This study retrospectively analyzed the performance of artificial neural networks (ANN) to predict overall survival (OS) or locoregional failure (LRF) in HNSCC patients undergoing radiotherapy, based on 2-[18F]FDG PET/CT and clinical covariates. We compared predictions relying on three different sets of features, extracted from 230 patients. Specifically, (i) an automated feature selection method independent of expert rating was compared with (ii) clinical variables with proven influence on OS or LRF and (iii) clinical data plus expert-selected SUV metrics. The three sets were given as input to an artificial neural network for outcome prediction, evaluated by Harrell's concordance index (HCI) and by testing stratification capability. For OS and LRF, the best performance was achieved with expert-based PET-features (0.71 HCI) and clinical variables (0.70 HCI), respectively. For OS stratification, all three feature sets were significant, whereas for LRF only expert-based PET-features successfully classified low vs. high-risk patients. Based on 2-[18F]FDG PET/CT features, stratification into risk groups using ANN for OS and LRF is possible. Differences in the results for different feature sets confirm the relevance of feature selection, and the key importance of expert knowledge vs. automated selection. [ABSTRACT FROM AUTHOR]