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Diffusion-weighted imaging (DWI) holds promise for image-guided radiotherapy (MRgRT) in prostate cancer. However, challenges persist due to image distortion, artifacts, and apparent diffusion coefficient (ADC) reproducibility issues. This study aimed to assess DWI image quality and ADC reproducibility on both a 1.5 T MR-simulator and a 1.5 T MR-Linac, employing measurements from both an ACR MRI phantom and prostate cancer patients undergoing MRgRT. DW-MRI scans were conducted on 19 patients (mean age = 69 ± 8 years, with 23 MR-visible intra-prostatic lesions) and an ACR MRI phantom using a 1.5 T MR-simulator (b-values = 0, 800, 1400s/mm2) and a 1.5 T MR-Linac (b-values = 50, 500, 800 s/mm2). ADC homogeneity in the phantom was evaluated via 1D profile flatness (FL) in three directions. Image quality was assessed through qualitative 5-point Likert scale ratings and quantitative ADC and signal-to-noise ratio (SNR) measurements. Intra-observer reproducibility of image quality scores was evaluated using ICC(1, 2). Geometric distortion was measured by comparing landmark sizes on the ACR phantom against the ground truth. Mean ADC and reproducibility were assessed using Bland-Altman plots. Both MR-simulator and MR-Linac demonstrated high ADC homogeneity (FL > 87.5% - MR-simulator: 97.23 ± 0.62%, MR-Linac: 94.75 ± 0.62%, p < 0.05) in the phantom. Image quality scores revealed acceptable ratings (≥3) for capsule demarcation, image artifacts, and geometric distortion in patients. However, intra-prostatic lesions were barely discernible in b800 images for both MR-simulator (average score = 2.37 ± 1.33) and MR-Linac (average score = 2.16 ± 1.28). While MR-Linac DWI scans exhibited significantly more severe geometric distortion than MR-simulator scans (p < 0.01), most phantom measurements fell within the image in-plane resolution of 3 mm. Significant differences were noted in MR-simulator ADC (CTV: 1.20 ± 0.14 × 10−3 mm2/s (MR-simulator) vs 1.06 ± 0.10 × 10–3 mm2/s (MR-Linac); GTV: 1.05 ± 0.21 × 10−3 mm2/s vs 0.91 ± 0.16 × 10 mm2/s, all p < 0.05), with a small non-zero bias observed in the Bland-Altman analysis (CTV: 12.3%; GTV: 14.5%). The significantly larger MR-simulator ADC and the small non-zero bias hint at potential systematic differences in ADC values acquired from an MR-simulator and an MR-Linac, both at 1.5 T. Although acceptable ADC homogeneity was noted, caution is warranted in interpreting MR-Linac DWI images due to occasional severe artifacts. Further studies are essential to validate DWI and ADC as reliable imaging markers in prostate cancer MRgRT. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the influence of the magnetic field on treatment plan quality using typical phantom test cases, which encompass a circle target test case, AAPM TG119 test cases (prostate, head-and-neck, C-shape, multi-target test cases), and a lung test case. Materials and Methods: For the typical phantom test cases, two plans were formulated. The first plan underwent optimization in the presence of a 1.5 Tesla magnetic field (1.5 T plan). The second plan was re-optimized without a magnetic field (0 T plan), utilizing the same optimization conditions as the first plan. The two plans were compared based on various parameters, including con-formity index (CI), homogeneity index (HI), fit index (FI) and dose coverage of the planning target volume (PTV), dose delivered to organs at risk (OARs) and normal tissue (NT), monitor unit (MU). A plan-quality metric (PQM) scoring procedure was employed. For the 1.5 T plans, dose verifications were performed using an MR-compatible ArcCHECK phantom. Results: A smaller dose influence of the magnetic field was found for the circle target, prostate, head-and-neck, and C-shape test cases, compared with the multi-target and lung test cases. In the multi-target test case, the significant dose influence was on the inferior PTV, followed by the superior PTV. There was a relatively large dose influence on the PTV and OARs for lung test case. No statistically significant differences in PQM and MUs were observed. For the 1.5 T plans, gamma passing rates were all higher than 95% with criteria of 2 mm/3% and 2 mm/2%. Conclusion: The presence of a 1.5 T magnetic field had a relatively large impact on dose parameters in the multi-target and lung test cases compared with other test cases. However, there were no significant influences on the plan-quality metric, MU and dose accuracy for all test cases. [ABSTRACT FROM AUTHOR]

Abstract Background Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study. Methods A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated. Results Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants. Conclusion Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.

Simple Summary: Adrenal metastases are frequent in solid malignancies such as lung cancer and melanoma. Recent studies support the use of ablative local therapies in oligometastatic or oligoprogressive patients. Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy. However, clinical data, especially the long-term results of this promising technique, are still limited. We here report the long-term outcomes of a large single-center cohort. (1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions The Alberta rotating biplanar linac‐MR has a 0.5 T magnetic field parallel to the beamline. When developing a new linac‐MR system, interactions of charged particles with the magnetic field necessitate careful consideration of skin dose and tissue interface effects.To investigate the effect of the magnetic field on skin dose using measurements and Monte Carlo (MC) simulations.We develop an MC model of our linac‐MR, which we validate by comparison with ion chamber measurements in a water tank. Additionally, MC simulation results are compared with radiochromic film surface dose measurements on solid water. Variations in surface dose as a function of field size are measured using a parallel plate ion chamber in solid water. Using an anthropomorphic computational phantom with a 2 mm‐thick skin layer, we investigate dose distributions resulting from three beam arrangements. Magnetic field on and off scenarios are considered for all measurements and simulations.For a 20 × 20 cm2 field size, D0.2cc${D_{0.2cc}}$ (the minimum dose to the hottest contiguous 0.2 cc volume) for the top 2 mm of a simple water phantom is 72% when the magnetic field is on, compared to 34% with magnetic field off (values are normalized to the central axis dose maximum). Parallel plate ion chamber measurements demonstrate that the relative increase in surface dose due to the magnetic field decreases with increasing field size. For the anthropomorphic phantom, D∼0.2cc${D_{ \sim 0.2cc}}$ (minimum skin dose in the hottest 1 × 1 × 1 cm3 cube) shows relative increases of 20%–28% when the magnetic field is on compared to when it is off. With magnetic field off, skin D∼0.2cc${D_{ \sim 0.2cc}}$ is 71%, 56%, and 21% for medial‐lateral tangents, anterior‐posterior beams, and a five‐field arrangement, respectively. For magnetic field on, the corresponding skin D∼0.2cc${D_{ \sim 0.2cc}}$ values are 91%, 67%, and 25%.Using a validated MC model of our linac‐MR, surface doses are calculated in various scenarios. MC‐calculated skin dose varies depending on field sizes, obliquity, and the number of beams. In general, the parallel linac‐MR arrangement results in skin dose enhancement due to charged particles spiraling along magnetic field lines, which impedes lateral motion away from the central axis. Nonetheless, considering the results presented herein, treatment plans can be designed to minimize skin dose by, for example, avoiding oblique beams and using a larger number of fields. [ABSTRACT FROM AUTHOR]

Background: Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study. Methods: A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated. Results: Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants. Conclusion: Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort. [ABSTRACT FROM AUTHOR]

Objectives Metallic implants cause artefacts and distortion on MRI. To ensure accurate dose delivery and plan adaptation on an MR Linac, there is a need to evaluate distortion caused. Methods Participants were imaged on an MR Linac (Elekta Unity, Elekta AB Stockholm). Three sequences were evaluated. Two vendor supplied (T2W TSE 3D), and one T2W TSE 3D optimized to reduce metal artefact distortions. Images were rigidly registered to CT images by a single observer, using bony anatomy. Three coronal and three axial images were selected, and six paired, adjacent, bony landmarks were identified on each slice. Images bisecting treatment isocentre were included. Difference between landmark coordinates was taken to be measure of distortion. Results Five observers participated. Thirty six pairs of bony landmarks were identified. Median difference in position of landmarks was ≤3 mm (range 0.3-4.4 mm). One-way analysis of variance (ANOVA) between observer means showed no significant variation between sequences or patients (P  = 1.26 in plane, P  = 0.11 through plane). Interobserver intra class correlation (ICC) was 0.70 in-plane and 0.78 through-plane. Intra-observer ICC for three observers was 0.76, 0.81, 0.83, showing moderate to good reliability on this small cohort. Conclusions This in-vivo feasibility study suggests distortion due to metallic hip prosthesis is not an obstacle for pelvic radiotherapy on an MR Linac. Research on the impact on plan quality is warranted. Advances in knowledge This work supports feasibility of treating patients with metallic hip prosthesis on an MR Linac. [ABSTRACT FROM AUTHOR]

Background: The static magnetic field present in magnetic resonance (MR)‐guided radiotherapy systems can influence dose deposition and charged particle collection in air‐filled ionization chambers. Thus, accurately quantifying the effect of the magnetic field on ionization chamber response is critical for output calibration. Formalisms for reference dosimetry in a magnetic field have been proposed, whereby a magnetic field quality conversion factor kB,Q is defined to account for the combined effects of the magnetic field on the radiation detector. Determination of kB,Q in the literature has focused on Monte Carlo simulation studies, with experimental validation limited to only a few ionization chamber models. Purpose: The purpose of this study is to experimentally measure kB,Q for 11 ionization chamber models in two commercially available MR‐guided radiotherapy systems: Elekta Unity and ViewRay MRIdian. Methods: Eleven ionization chamber models were characterized in this study: Exradin A12, A12S, A28, and A26, PTW T31010, T31021, and T31022, and IBA FC23‐C, CC25, CC13, and CC08. The experimental method to measure kB,Q utilized cross‐calibration against a reference Exradin A1SL chamber. Absorbed dose to water was measured for the reference A1SL chamber positioned parallel to the magnetic field with its centroid placed at the machine isocenter at a depth of 10 cm in water for a 10 × 10 cm2 field size at that depth. Output was subsequently measured with the test chamber at the same point of measurement. kB,Q for the test chamber was computed as the ratio of reference dose to test chamber output, with this procedure repeated for each chamber in each MR‐guided radiotherapy system. For the high‐field 1.5 T Elekta Unity system, the dependence of kB,Q on the chamber orientation relative to the magnetic field was quantified by rotating the chamber about the machine isocenter. Results: Measured kB,Q values for our test dataset of ionization chamber models ranged from 0.991 to 1.002, and 0.995 to 1.004 for the Elekta Unity and ViewRay MRIdian, respectively, with kB,Q tending to increase as the chamber sensitive volume increased. Measured kB,Q values largely agreed within uncertainty to published Monte Carlo simulation data and available experimental data. kB,Q deviation from unity was minimized for ionization chamber orientation parallel or antiparallel to the magnetic field, with increased deviations observed at perpendicular orientations. Overall (k = 1) uncertainty in the experimental determination of the magnetic field quality conversion factor, kB,Q was 0.71% and 0.72% for the Elekta Unity and ViewRay MRIdian systems, respectively. Conclusions: For a high‐field MR‐linac, the characterization of ionization chamber performance as angular orientation varied relative to the magnetic field confirmed that the ideal orientation for output calibration is parallel. For most of these chamber models, this study represents the first experimental characterization of chamber performance in clinical MR‐linac beams. This is a critical step toward accurate output calibration for MR‐guided radiotherapy systems and the measured kB,Q values will be an important reference data source for forthcoming MR‐linac reference dosimetry protocols. [ABSTRACT FROM AUTHOR]

Background: Volumetric reconstruction of magnetic resonance imaging (MRI) from sparse samples is desirable for 3D motion tracking and promises to improve magnetic resonance (MR)‐guided radiation treatment precision. Data‐driven sparse MRI reconstruction, however, requires large‐scale training datasets for prior learning, which is time‐consuming and challenging to acquire in clinical settings. Purpose: To investigate volumetric reconstruction of MRI from sparse samples of two orthogonal slices aided by sparse priors of two static 3D MRI through implicit neural representation (NeRP) learning, in support of 3D motion tracking during MR‐guided radiotherapy. Methods: A multi‐layer perceptron network was trained to parameterize the NeRP model of a patient‐specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first training the network to learn the NeRP of two static 3D MRI with different breathing motion states, prior information of patient breathing motion was embedded into network weights through optimization. The prior information was then augmented from two motion states to 31 motion states by querying the optimized network at interpolated and extrapolated motion state coordinates. Starting from the prior‐augmented NeRP model as an initialization point, we further trained the network to fit sparse samples of two orthogonal MRI slices and the final volumetric reconstruction was obtained by querying the trained network at 3D spatial locations. We evaluated the proposed method using 5‐min volumetric MRI time series with 340 ms temporal resolution for seven abdominal patients with hepatocellular carcinoma, acquired using golden‐angle radial MRI sequence and reconstructed through retrospective sorting. Two volumetric MRI with inhale and exhale states respectively were selected from the first 30 s of the time series for prior embedding and augmentation. The remaining 4.5‐min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to two orthogonal slices and compared model‐reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. Results: Across the seven patients evaluated, the peak signal‐to‐noise‐ratio between model‐reconstructed and ground truth MR images was 38.02 ± 2.60 dB and the structure similarity index measure was 0.98 ± 0.01. Throughout the 4.5‐min time period, gross tumor volume (GTV) motion estimated by deforming a reference state MRI to model‐reconstructed and ground truth MRI showed good consistency. The 95‐percentile Hausdorff distance between GTV contours was 2.41 ± 0.77 mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1 mm in all three orthogonal directions. Conclusion: A prior‐augmented NeRP model has been developed to reconstruct volumetric MRI from sparse samples of orthogonal cine slices. Only one exhale and one inhale 3D MRI were needed to train the model to learn prior information of patient breathing motion for sparse image reconstruction. The proposed model has the potential of supporting 3D motion tracking during MR‐guided radiotherapy for improved treatment precision and promises a major simplification of the workflow by eliminating the need for large‐scale training datasets. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma is a malignant tumor with a poor prognosis and a frequent metastatic extension. In very rare cases, a cardiac metastatic disease may occur, and surgical resection is essential for its management. MR-guided stereotactic radiotherapy is an attractive radiotherapy modality for the treatment of mobile thoracic tumors, enabling the target to be monitored continuously during irradiation, while the dosimetric plan can be adapted daily if necessary. We report here the case of a patient with intracardiac metastasis secondary to malignant adrenocortical carcinoma, treated with magnetic resonance imaging-guided stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. Methods: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. Results: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). Conclusion: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients. [ABSTRACT FROM AUTHOR]

We present two cases of cardiac metastases adjacent to the right ventricle in a 55-year-old male and a 61-year-old female, both treated with magnetic resonance (MR)-guided adaptive stereotactic radiation therapy (SBRT). The prescribed regimen was 30Gy delivered in 3 fractions using a 1.5 Tesla magnetic resonance linear accelerator (MR-linac). Patients exhibited favorable tolerance to the treatment, with no observed acute toxicity.

Background and purpose: Peer review is an important component of quality assurance in radiotherapy. To our knowledge, there are no studies reporting on the feasibility and outcomes of the peer review process for magnetic resonance (MR) guided radiotherapy (MRgRT) on the MR linear accelerator (MR-Linac) despite the planning complexity involved and its evolving clinical indications. This study aimed to quantify the rate of change in treatment plans post-peer review and the time and resources required. Materials and methods: Fifty-five cases presented at weekly MR-Linac peer review meetings across two centres from 8 June to 21 September 2023 were prospectively collected. Cases were analysed to determine the rate and extent of plan changes based on the Peer Review Audit Tool for radiation oncology (PRAT) developed by the Royal Australian and New Zealand College of Radiologists (RANZCR). Results: Peer review resulted in changes to 36.4 % of treatment plans (n = 20), with 3.6 % (n = 2) having major changes requiring deferment of treatment. The most frequent changes were to organs at risk (OAR) volumes involving both delineation and increased OAR sparing (16.4 %, n = 9), total dose and fractionation (10.9 %, n = 6) and target volume dose coverage (5.5 %, n = 3). Patients with SBRT plans (39.1 % cf 22.2 %), oligometastatic/oligoprogressive sites (38.1 % cf 30.7 %) and reirradiation cases (41.2 % cf 34.2 %) had higher rates of change. Cases took a mean of 7 min (range 2–15 minutes) to discuss. Conclusion: The high rates of plan changes support the value of peer review in MRgRT. We recommend, where possible that all MRgRT cases, particularly those involving SBRT plans, oligometastatic/oligoprogressive sites, and/or reirradiation, be subject to peer review.

Background and purpose: MR-guided radiotherapy adds the precision of magnetic resonance imaging (MRI) to the therapeutic benefits of a linear accelerator. Prior to each therapeutic session, an MRI generates a significant volume of imaging data ripe for analysis. Radiomics stands at the forefront of medical imaging and oncology research, dedicated to mining quantitative imaging attributes to forge predictive models. However, the robustness of these models is often challenged. Materials and methods: To assess the robustness of feature extraction, we conducted reproducibility studies using a 0.35 T MR-linac system, employing both a specialized phantom and patient-derived images, focusing on cases of pancreatic cancer. We extracted shape-based, first-order and textural features from patient-derived images and only first-order and textural features from phantom-derived images. The impact of the delay between simulation and first fraction images was also assessed with an equivalence test. Results: From 107 features evaluated, 58 (54 %) were considered as non-reproducible: 18 were uniformly inconsistent across both phantom and patient images, 9 were specific to phantom-based analysis, and 31 to patient-derived data. Conclusion: Our findings show that a significant proportion of radiomic features extracted from this dual dataset were unreliable. It is essential to discard these non-reproducible elements to refine and enhance radiomic model development, particularly for MR-guided radiotherapy in pancreatic cancer.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often >2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

Abstract 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.

Simple Summary: Daily adaptation of the radiation plan on the treatment couch has the potential to reduce toxicity to healthy tissue while maintaining the dose or even enabling higher doses applied to cancerous tissue. However, current approaches either require more time and personnel to perform plan adaptation or lack resolution for soft tissue contrast. The Ethos radiotherapy device utilizes artificial intelligence and machine learning to allow rapid plan adaptation based on the daily anatomy. We here outline the first workflow in which we combine the Ethos machine with weekly magnetic resonance imaging, the gold standard for soft tissue resolution. This is facilitated by a shuttle system that allows patients to be transported from one device to the other in treatment position. Purpose: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance. Methods: From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients. Results: In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5–63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7–39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6–32.2), 0.4 min (IQR 0.3–1,0) and 5.3 min (IQR 4.5–6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases. Conclusion: This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system. [ABSTRACT FROM AUTHOR]

Objective. Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods. Approach. We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients. Main results. The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3 isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data. Significance. The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating. [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]

Simple Summary: This paper presents a novel approach to produce virtual contrast enhanced (VCE) images for nasopharyngeal cancer (NPC) without the use of contrast agents, which carry certain risks. This model uses pixelwise gradient term to capture the shape and a GAN terms to capture the texture of the real contrast enhanced T1C images With similar accuracy to existing models, our method shows an advantage in reproducing texture closer to the realistic contrast-enhanced images. This results are tested by various measures, including mean absolute error (MAE), mean square error (MSE) and structural similarity index (SSIM) for similarity accuracy; total mean square variation per mean intensity (TMSVPMI), the total absolute vari-ation per mean intensity (TAVPMI), Tenengrad function per mean intensity (TFPMI) and variance function per mean intensity (VFPMI) Various variations of the model, including fine-tuning of the hyperparameters, normalization methods on the images and using single modality, have also been investigated to test the optimal performance. Background: The development of advanced computational models for medical imaging is crucial for improving diagnostic accuracy in healthcare. This paper introduces a novel approach for virtual contrast enhancement (VCE) in magnetic resonance imaging (MRI), particularly focusing on nasopharyngeal cancer (NPC). Methods: The proposed model, Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement (PGMGVCE), makes use of pixelwise gradient methods with Generative Adversarial Networks (GANs) to enhance T1-weighted (T1-w) and T2-weighted (T2-w) MRI images. This approach combines the benefits of both modalities to simulate the effects of gadolinium-based contrast agents, thereby reducing associated risks. Various modifications of PGMGVCE, including changing hyperparameters, using normalization methods (z-score, Sigmoid and Tanh) and training the model with T1-w or T2-w images only, were tested to optimize the model's performance. Results: PGMGVCE demonstrated a similar accuracy to the existing model in terms of mean absolute error (MAE) (8.56 ± 0.45 for Li's model; 8.72 ± 0.48 for PGMGVCE), mean square error (MSE) (12.43 ± 0.67 for Li's model; 12.81 ± 0.73 for PGMGVCE) and structural similarity index (SSIM) (0.71 ± 0.08 for Li's model; 0.73 ± 0.12 for PGMGVCE). However, it showed improvements in texture representation, as indicated by total mean square variation per mean intensity (TMSVPMI) (0.124 ± 0.022 for ground truth; 0.079 ± 0.024 for Li's model; 0.120 ± 0.027 for PGMGVCE), total absolute variation per mean intensity (TAVPMI) (0.159 ± 0.031 for ground truth; 0.100 ± 0.032 for Li's model; 0.153 ± 0.029 for PGMGVCE), Tenengrad function per mean intensity (TFPMI) (1.222 ± 0.241 for ground truth; 0.981 ± 0.213 for Li's model; 1.194 ± 0.223 for PGMGVCE) and variance function per mean intensity (VFPMI) (0.0811 ± 0.005 for ground truth; 0.0667   ± 0.006 for Li's model; 0.0761   ± 0.006 for PGMGVCE). Conclusions: PGMGVCE presents an innovative and safe approach to VCE in MRI, demonstrating the power of deep learning in enhancing medical imaging. This model paves the way for more accurate and risk-free diagnostic tools in medical imaging. [ABSTRACT FROM AUTHOR]

Background: Apart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer. Materials and methods: 32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models. Results: In 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage =95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage =98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were <38.5 Gy in 93% vs. 100% before and after online adaptation. The constraint at the urethra with a dose of <37.5 Gy was achieved in 59% vs. 93% before and after online adaptation. Conclusion: Online adaptive plan adaptation improves target volume coverage and reduces doses to OAR in MR-guided SBRT of localized prostate cancer. Online plan adaptation could potentially further reduce acute and long-term side effects and improve local failure rates in MR-guided SBRT of localized prostate cancer. [ABSTRACT FROM AUTHOR]

We report the case of an 87-year-old woman with upper tract urothelial carcinoma at the left renal pelvis. She received stereotactic body radiotherapy of 35 Gy in five fractions for palliative treatment of hematuria that was delivered by a 1.5-T magnetic resonance (MR) imaging-guided linear accelerator. Her symptom was relieved after treatment, and posttreatment imaging revealed a complete response of the primary tumor. Thus, this case showed that stereotactic MR-guided radiotherapy could be an appealing option for inoperable patients although radiotherapy is infrequently mentioned in the current treatment guideline of upper tract urothelial carcinoma. Daily adaptive planning from MR images obtained before treatment could improve the target dose and minimize the organ at risk dose. This may lead to a decrease in radiation adverse effects including worsening renal function due to the renal pelvis tumor's proximity to the kidney. [ABSTRACT FROM AUTHOR]

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Background and Purpose: Standard imaging protocols can guarantee the spatial integrity of magnetic resonance (MR) images utilized in radiotherapy. However, the presence of metallic implants can significantly compromise this integrity. Our proposed method aims at characterizing the geometric distortions induced by both passive and active implants commonly encountered in planning images obtained from a low-field 0.35 T MR-linear accelerator (LINAC). Materials and Methods: We designed a spatial integrity phantom defining 1276 control points and covering a field of view of 20x20x20 cm3. This phantom was scanned in a water tank with and without different implants used in hip and shoulder arthroplasty procedures as well as with active cardiac stimulators. The images were acquired with the clinical planning sequence (balanced steady-state free-precession, resolution 1.5x1.5x1.5 mm3). Spatial integrity was assessed by the Euclidian distance between the control point detected on the image and their theoretical locations. A first plane free of artefact (FPFA) was defined to evaluate the spatial integrity beyond the larger banding artefact. Results: In the region extending up to 20 mm from the largest banding artefacts, the tested passive and active implants could cause distortions up to 2 mm and 3 mm, respectively. Beyond this region the spatial integrity was recovered and the image could be considered as unaffected by the implants. Conclusions: We characterized the impact of common implants on a low field MR-LINAC planning sequence. These measurements could support the creation of extra margin while contouring organs at risk and target volumes in the vicinity of implants.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Background and purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019–2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P

Background: The aim of this prospective observational study was to evaluate the dosimetry benefits, changes in pulmonary function, and clinical outcome of online adaptive MR-guided SBRT. Methods: From 11/2020–07/2022, 45 consecutive patients with 59 lesions underwent multi-fraction SBRT (3–8 fractions) at our institution. Patients were eligible if they had biopsy-proven NSCLC or lung cancer/metastases diagnosed via clinical imaging. Endpoints were local control (LC) and overall survival (OS). We evaluated PTV/GTV dose coverage, organs at risk exposure, and changes in pulmonary function (PF). Acute toxicity was classified per the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Results: The median PTV was 14.4 cm3 (range: 3.4 – 96.5 cm3). In total 195/215 (91%) plans were reoptimised. In the reoptimised vs. predicted plans, PTV coverage by the prescribed dose increased in 94.6% of all fractions with a median increase in PTV VPD of 5.6% (range: −1.8 – 44.6%, p

Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p

BackgroundApart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer.Materials and methods32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models.ResultsIn 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage ≥95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage ≥98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT.

PurposeTo estimate the overall spatial distortion on clinical patient images for a 0.35 T MR-guided radiotherapy system.MethodsTen patients with head-and-neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post-processing. The images were rigidly registered and landmark-based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone-tissue, soft tissue, or air-tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed.ResultsThe average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0-1 mm. 66% of the discrepancies were

Abstract Background Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Abstract Background Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Methods Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. Discussion PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. Trial registration ClinicalTrials.gov: NCT05237453 .

Background and purpose: Magnetic Resonance Imaging (MRI) is widely used in oncology for tumor staging, treatment response assessment, and radiation therapy (RT) planning. This study proposes a framework for automatic optimization of MRI sequences based on pulse sequence parameter sets (SPS) that are directly applied on the scanner, for application in RT planning. Materials and methods: A phantom with seven in-house fabricated contrasts was used for measurements. The proposed framework employed a derivative-free optimization algorithm to repeatedly update and execute a parametrized sequence on the MR scanner to acquire new data. In each iteration, the mean-square error was calculated based on the clinical application. Two clinically relevant optimization goals were pursued: achieving the same signal and therefore contrast as in a target image, and maximizing the signal difference (contrast) between specified tissue types. The framework was evaluated using two optimization methods: a covariance matrix adaptation evolution strategy (CMA-ES) and a genetic algorithm (GA). Results: The obtained results demonstrated the potential of the proposed framework for automatic optimization of MRI sequences. Both CMA-ES and GA methods showed promising results in achieving the two optimization goals, however, CMA-ES converged much faster as compared to GA. Conclusions: The proposed framework enables for automatic optimization of MRI sequences based on SPS that are directly applied on the scanner and it may be used to enhance the quality of MRI images for dedicated applications in MR-guided RT.

In the past few years, radiotherapy (RT) has experienced a major technological innovation with the development of hybrid machines combining magnetic resonance (MR) imaging and linear accelerators. This new technology for MR-guided cancer treatment has the potential to revolutionize the field of adaptive RT due to the opportunity to provide high-resolution, real-time MR imaging before and during treatment application. However, from a technical point of view, several challenges remain which need to be tackled to ensure safe and robust real-time adaptive MR-guided RT delivery. In this manuscript, several technical challenges to MR-guided RT are discussed. Starting with magnetic field strength tradeoffs, the potential and limitations for purely MR-based RT workflows are discussed. Furthermore, the current status of real-time 3D MR imaging and its potential for real-time RT are summarized. Finally, the potential of quantitative MR imaging for future biological RT adaptation is highlighted.

Background: Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes. Methods: Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers’ delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated. Results: Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p

Purpose: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance. Methods: From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients. Results: In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5–63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7–39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6–32.2), 0.4 min (IQR 0.3–1,0) and 5.3 min (IQR 4.5–6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases. Conclusion: This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system.

Background: The development of advanced computational models for medical imaging is crucial for improving diagnostic accuracy in healthcare. This paper introduces a novel approach for virtual contrast enhancement (VCE) in magnetic resonance imaging (MRI), particularly focusing on nasopharyngeal cancer (NPC). Methods: The proposed model, Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement (PGMGVCE), makes use of pixelwise gradient methods with Generative Adversarial Networks (GANs) to enhance T1-weighted (T1-w) and T2-weighted (T2-w) MRI images. This approach combines the benefits of both modalities to simulate the effects of gadolinium-based contrast agents, thereby reducing associated risks. Various modifications of PGMGVCE, including changing hyperparameters, using normalization methods (z-score, Sigmoid and Tanh) and training the model with T1-w or T2-w images only, were tested to optimize the model’s performance. Results: PGMGVCE demonstrated a similar accuracy to the existing model in terms of mean absolute error (MAE) (8.56 ± 0.45 for Li’s model; 8.72 ± 0.48 for PGMGVCE), mean square error (MSE) (12.43 ± 0.67 for Li’s model; 12.81 ± 0.73 for PGMGVCE) and structural similarity index (SSIM) (0.71 ± 0.08 for Li’s model; 0.73 ± 0.12 for PGMGVCE). However, it showed improvements in texture representation, as indicated by total mean square variation per mean intensity (TMSVPMI) (0.124 ± 0.022 for ground truth; 0.079 ± 0.024 for Li’s model; 0.120 ± 0.027 for PGMGVCE), total absolute variation per mean intensity (TAVPMI) (0.159 ± 0.031 for ground truth; 0.100 ± 0.032 for Li’s model; 0.153 ± 0.029 for PGMGVCE), Tenengrad function per mean intensity (TFPMI) (1.222 ± 0.241 for ground truth; 0.981 ± 0.213 for Li’s model; 1.194 ± 0.223 for PGMGVCE) and variance function per mean intensity (VFPMI) (0.0811 ± 0.005 for ground truth; 0.0667 ± 0.006 for Li’s model; 0.0761 ± 0.006 for PGMGVCE). Conclusions: PGMGVCE presents an innovative and safe approach to VCE in MRI, demonstrating the power of deep learning in enhancing medical imaging. This model paves the way for more accurate and risk-free diagnostic tools in medical imaging.

Background and purpose: Physiological motion impacts the dose delivered to tumours and vital organs in external beam radiotherapy and particularly in particle therapy. The excellent soft-tissue demarcation of 4D magnetic resonance imaging (4D-MRI) could inform on intra-fractional motion, but long image reconstruction times hinder its use in online treatment adaptation. Here we employ techniques from high-performance computing to reduce 4D-MRI reconstruction times below two minutes to facilitate their use in MR-guided radiotherapy. Material and methods: Four patients with pancreatic adenocarcinoma were scanned with a radial stack-of-stars gradient echo sequence on a 1.5T MR-Linac. Fast parallelised open-source implementations of the extra-dimensional golden-angle radial sparse parallel algorithm were developed for central processing unit (CPU) and graphics processing unit (GPU) architectures. We assessed the impact of architecture, oversampling and respiratory binning strategy on 4D-MRI reconstruction time and compared images using the structural similarity (SSIM) index against a MATLAB reference implementation. Scaling and bottlenecks for the different architectures were studied using multi-GPU systems. Results: All reconstructed 4D-MRI were identical to the reference implementation (SSIM > 0.99). Images reconstructed with overlapping respiratory bins were sharper at the cost of longer reconstruction times. The CPU + GPU implementation was over 17 times faster than the reference implementation, reconstructing images in 60 ± 1 s and hyper-scaled using multiple GPUs. Conclusion: Respiratory-resolved 4D-MRI reconstruction times can be reduced using high-performance computing methods for online workflows in MR-guided radiotherapy with potential applications in particle therapy.

Background and Purpose: In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs. Materials and Methods: MLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan. Results: All positions in the motor step – position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2 ± 0.1 mm for X1 (left bank) and 0.2 ± 0.2 mm for X2 (right bank). The accuracy of the leaf position evaluation was 0.2 mm (95% confidence level). The MLC calibration remained stable over four months. Small MLC leaf position errors (e.g. 1.2 mm field size reduction) resulted in important dose errors (−5.8 %) for small quadratic fields of 0.83 × 0.83 cm2. Single stack position accuracy was essential for highly modulated treatment plans. Conclusions: LIMCA is a new double stack MLC calibration method that increases treatment accuracy from four angles and for all moving leaves.

Background and purpose: The superior tissue contrast of magnetic resonance (MR) compared to computed tomography (CT) led to an increasing interest towards MR-only radiotherapy. For the latter, the dose calculation should be performed on a synthetic CT (sCT). Patient-specific quality assurance (PSQA) methods have not been established yet and this study aimed to assess several software-based solutions. Materials and methods: A retrospective study was performed on 20 patients treated at an MR-Linac, which were selected to evenly cover four subcategories: (i) standard, (ii) air pockets, (iii) lung and (iv) implant cases. The neural network (NN) CycleGAN was adopted to generate a reference sCT, which was then compared to four PSQA methods: (A) water override of body, (B) five tissue classes with bulk densities, (C) sCT generated by a separate NN (pix2pix) and (D) deformed CT. Results: The evaluation of the dose endpoints demonstrated that while all methods A-D provided statistically equivalent results (p = 0.05) within the 2% level for the standard cases (i), only the methods C-D guaranteed the same result over the whole cohort. The bulk densities override was shown to be a valuable method in absence of lung tissue within the beam path. Conclusion: The observations of this study suggested that the use of an additional sCT generated by a separate NN was an appropriate tool to perform PSQA of a sCT in an MR-only workflow at an MR-Linac. The time and dose endpoints requirements were respected, namely within 10 min and 2%.

Background: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Methods: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. Discussion: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. Trial registration: ClinicalTrials.gov: NCT05237453. [ABSTRACT FROM AUTHOR]

Background: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722). [ABSTRACT FROM AUTHOR]

Background: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Methods: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. Discussion: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. Trial registration: ClinicalTrials.gov: NCT05237453. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential value of MRI radiomics obtained from a 1.5 T MRI‐guided linear accelerator (MR‐LINAC) for D'Amico high‐risk prostate cancer (PC) classification in MR‐guided radiotherapy (MRgRT). Methods: One hundred seventy‐six consecutive PC patients underwent 1.5 T MRgRT treatment were retrospectively enrolled. Each patient received one or two pretreatment T2‐weighted MRI scans on a 1.5 T MR‐LINAC. The endpoint was to differentiate high‐risk from low/intermediate‐risk PC based on D'Amico criteria using MRI‐radiomics. Totally 1023 features were extracted from clinical target volume (CTV) and planning target volume (PTV). Intraclass correlation coefficient of scan–rescan repeatability, feature correlation, and recursive feature elimination were used for feature dimension reduction. Least absolute shrinkage and selection operator regression was employed for model construction. Receiver operating characteristic area under the curve (AUC) analysis was used for model performance assessment in both training and testing data. Results: One hundred and eleven patients fulfilled all criteria were finally included: 76 for training and 35 for testing. The constructed MRI‐radiomics models extracted from CTV and PTV achieved the AUC of 0.812 and 0.867 in the training data, without significant difference (P = 0.083). The model performances remained in the testing. The sensitivity, specificity, and accuracy were 85.71%, 64.29%, and 77.14% for the PTV‐based model; and 71.43%, 71.43%, and 71.43% for the CTV‐based model. The corresponding AUCs were 0.718 and 0.750 (P = 0.091) for CTV‐ and PTV‐based models. Conclusion: MRI‐radiomics obtained from a 1.5 T MR‐LINAC showed promising results in D'Amico high‐risk PC stratification, potentially helpful for the future PC MRgRT. Prospective studies with larger sample sizes and external validation are warranted for further verification. [ABSTRACT FROM AUTHOR]