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Purpose: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than to whole-heart metrics. Magnetic resonance (MR)-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning framework, "No New" U-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT., Methods and Materials: Eighteen (institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linear accelerator were retrospectively evaluated. On each image, 1 of 2 radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n = 10), validate (n = 3), and test (n = 5) nnU-Net.wSD by leveraging a teacher-student network and comparing it to standard 3-dimensional U-Net. The impact of using simulation data or including 3 to 4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient, mean distance to agreement, and 95% Hausdorff distance), visual inspection, and clinical dose-volume histograms were evaluated. To determine generalizability, institute A's model was tested on an unlabeled data set from institute B (n = 22) and evaluated via consensus scoring and volume comparisons., Results: nnU-Net.wSD yielded a Dice similarity coefficient (reported mean ± SD) of 0.65 ± 0.25 across the 12 substructures (chambers, 0.85 ± 0.05; great vessels, 0.67 ± 0.19; and coronary arteries, 0.33 ± 0.16; mean distance to agreement, <3 mm; mean 95% Hausdorff distance, <9 mm) while outperforming the 3-dimensional U-Net (0.583 ± 0.28; P <.01). Leveraging fractionated data for augmentation improved over a single MR simulation time point (0.579 ± 0.29; P <.01). Predicted contours yielded dose-volume histograms that closely matched those of the clinical treatment plans where mean and maximum (ie, dose to 0.03 cc) doses deviated by 0.32 ± 0.5 Gy and 1.42 ± 2.6 Gy, respectively. There were no statistically significant differences between institute A and B volumes (P >.05) for 11 of 12 substructures, with larger volumes requiring minor changes and coronary arteries exhibiting more variability., Conclusions: This work is a critical step toward rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Magnetic resonance (MR)-guided radiation therapy enables online adaptation to address intra- and interfractional changes. To address the need of high-fidelity synthetic computed tomography (synCT) required for dose calculation, we developed a conditional generative adversarial network for synCT generation from low-field MR imaging in the brain., Methods and Materials: Simulation MR-CT pairs from 12 patients with glioma imaged with a head and neck surface coil and treated on a 0.35T MR-linac were prospectively included to train the model consisting of a 9-block residual network generator and a PatchGAN discriminator. Four-fold cross-validation was implemented. SynCT was quantitatively evaluated against real CT using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). Dose was calculated on synCT applying original treatment plan. Dosimetric performance was evaluated by dose-volume histogram metric comparison and local 3-dimensional gamma analysis. To demonstrate utilization in treatment adaptation, longitudinal synCTs were generated for qualitative evaluation, and 1 offline adaptation case underwent 2 comparative plan evaluations. Secondary validation was conducted with 9 patients on a different MR-linac using a high-resolution brain coil., Results: Our model generated high-quality synCTs with MAE, PSNR, and SSIM of 70.9 ± 10.4 HU, 28.4 ± 1.5 dB, and 0.87 ± 0.02 within the field of view, respectively. Underrepresented postsurgical anomalies challenged model performance. Nevertheless, excellent dosimetric agreement was observed with the mean difference between real and synCT dose-volume histogram metrics of -0.07 ± 0.29 Gy for target D 95 and within [-0.14, 0.02] Gy for organs at risk. Significant differences were only observed in the right lens D 0.01cc with negligible overall difference (<0.13 Gy). Mean gamma analysis pass rates were 92.2% ± 3.0%, 99.2% ± 0.7%, and 99.9% ± 0.1% at 1%/1 mm, 2%/2 mm, and 3%/3 mm, respectively. Secondary validation yielded no significant differences in synCT performance for whole-brain MAE, PSNR, and SSIM with comparable dosimetric results., Conclusions: Our conditional generative adversarial network model generated high-fidelity brain synCTs from low-field MR imaging with excellent dosimetric performance. Secondary validation suggests great promise of implementing synCTs to facilitate robust dose calculation for online adaptive brain MR-guided radiation therapy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT)., Purpose: This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom., Methods: The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3 mm peak-to-peak, 60 beats/min), respiratory (cos 4 waveform, 30 mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4 mm peak-to-peak, 70 beats/min) and respiratory (cos 4 waveform, 24 mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4 mm × 2.4 mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated., Results: No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3 ± 25.8%/66.9 ± 14.0%, 97.0 ± 2.2%/96.4 ± 1.7%, and 90.4 ± 4.8%/89.3 ± 3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was <2% from expected using the IC module. Real-time dose measured for the PSDs at 10 Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was <1% from expected (5-6 cGy deviation of 5.9 Gy/fraction) and high gradient/low dose regions had deviations <3.6% (6.3 cGy less than expected 1.73 Gy/fraction)., Conclusions: A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: MRI-guided radiation therapy (MRgRT) requires unique quality assurance equipment to address MR-compatibility needs, minimize electron return effect, handle complex dose distributions, and evaluate real-time dosimetry for gating. Plastic scintillation detectors (PSDs) are an attractive option to address these needs., Purpose: To perform a comprehensive characterization of a multi-probe PSD system in a low-field 0.35 T MR-linac, including detector response assessment and gating performance., Methods: A four-channel PSD system (HYPERSCINT RP-200) was assembled. A single channel was used to evaluate repeatability, percent depth dose (PDD), detector response as a function of orientation with respect to the magnetic field, and intersession variability. All four channels were used to evaluate repeatability, linearity, and output factors. The four PSDs were integrated into an MR-compatible motion phantom at isocenter and in gradient regions. Experiments were conducted to evaluate gating performance and tracking efficacy., Results: For repeatability, the maximum standard deviation of repeated measurements was 0.13% (single PSD). Comparing the PSD to reference data, PDD had a maximum difference of 1.12% (10 cm depth, 6.64 × 6.64 cm 2 ). Percent differences for rotated detector setups were negligible (< 0.3%). All four PSDs demonstrated linear response over 10-1000 MU delivered and the maximum percent difference between the baseline and measured output factors was 0.78% (2.49 × 2.49 cm 2 ). Gating experiments had 400 cGy delivered to isocenter with < 0.8 cGy variation for central axis measures and < 0.7 cGy for the gradient sampled region. Real-time dosimetry measurements captured spurious beam-on incidents that correlated to tracking algorithm inaccuracies and highlighted gating parameter impact on delivery efficiency., Conclusions: Characterization of the multi-point PSD dosimetry system in a 0.35 T MR-linac demonstrated reliability in a low-field MR-Linac setting, with high repeatability, linearity, small intersession variability, and similarity to baseline data for PDD and output factors. Time-resolved, multi-point dosimetry also showed considerable promise for gated MR-Linac applications., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: T 1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T 1 mapping technique, using acquisition details from a seminal T 1 mapping paper on a standardized phantom and in human brains., Methods: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T 1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed., Results: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org., Conclusion: The T 1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T 1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T 1 variations in vivo., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment., (© 2024 American Association of Physicists in Medicine.)

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 k B,Q is defined to account for the combined effects of the magnetic field on the radiation detector. Determination of k B,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 k B,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 k B,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 cm 2 field size at that depth. Output was subsequently measured with the test chamber at the same point of measurement. k B,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 k B,Q on the chamber orientation relative to the magnetic field was quantified by rotating the chamber about the machine isocenter., Results: Measured k B,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 k B,Q tending to increase as the chamber sensitive volume increased. Measured k B,Q values largely agreed within uncertainty to published Monte Carlo simulation data and available experimental data. k B,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, k B,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 k B,Q values will be an important reference data source for forthcoming MR-linac reference dosimetry protocols., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background and Purpose: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity., Materials and Methods: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose 10 [BED 10 ] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART., Results: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively., Conclusions: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Pulsed reduced dose rate (PRDR) is an emerging radiotherapy technique for recurrent diseases. It is pertinent that the linac beam characteristics are evaluated for PRDR dose rates and a suitable dosimeter is employed for IMRT QA., Purpose: This study sought to investigate the pulse characteristics of a 6 MV photon beam during PRDR irradiations on a commercial linac. The feasibility of using EBT3 radiochromic film for use in IMRT QA was also investigated by comparing its response to a commercial diode array phantom., Methods: A plastic scintillator detector was employed to measure the photon pulse characteristics across nominal repetition rates (NRRs) in the 5-600 MU/min range. Film was irradiated with dose rates in the 0.033-4 Gy/min range to study the dose rate dependence. Five clinical PRDR treatment plans were selected for IMRT QA with the Delta4 phantom and EBT3 film sheets. The planned and measured dose were compared using gamma analysis with a criterion of 3%/3 mm. EBT3 film QA was performed using a cumulative technique and a weighting factor technique., Results: Negligible differences were observed in the pulse width and height data between the investigated NRRs. The pulse width was measured to be 3.15 ± 0.01 μ s $\mu s$ and the PRF was calculated to be 3-357 Hz for the 5-600 MU/min NRRs. The EBT3 film was found to be dose rate independent within 3%. The gamma pass rates (GPRs) were above 99% and 90% for the Delta4 phantom and the EBT3 film using the cumulative QA method, respectively. GPRs as low as 80% were noted for the weighting factor EBT3 QA method., Conclusions: Altering the NRRs changes the mean dose rate while the instantaneous dose rate remains constant. The EBT3 film was found to be suitable for PRDR dosimetry and IMRT QA with minimal dose rate dependence., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Purpose: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC)., Methods and Materials: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART., Results: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%., Conclusions: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI) has become an important imaging modality in the field of radiotherapy (RT) in the past decade, especially with the development of various novel MRI and image-guidance techniques. In this review article, we will describe recent developments and discuss the applications of multi-parametric MRI (mpMRI) in RT simulation. In this review, mpMRI refers to a general and loose definition which includes various multi-contrast MRI techniques. Specifically, we will focus on the implementation, challenges, and future directions of mpMRI techniques for RT simulation., (© 2023 American Association of Physicists in Medicine.)

In this paper, we proposed MAGNET, a novel modality-agnostic network for 3D medical image segmentation. Different from existing learning methods, MAGNET is specifically designed to handle real medical situations where multiple modalities/sequences are available during model training, but fewer ones are available or used at time of clinical practice. Our results on multiple datasets show that MAGNET trained on multi-modality data has the unique ability to perform predictions using any subset of training imaging modalities. It outperforms individually trained uni-modality models while can further boost performance when more modalities are available at testing.

Purpose: To reduce scan time, methods to accelerate phase-encoded/non-Cartesian MR fingerprinting (MRF) acquisitions for variable density spiral acquisitions have recently been developed. These methods are not applicable to MRF acquisitions, wherein a single k-space spoke is acquired per frame. Therefore, we propose a low-rank inversion method to resolve MRF contrast dynamics from through-plane accelerated Cartesian/radial measurements applied to quantitative relaxation-time mapping on a 0.35T system., Methods: An algorithm was implemented to reconstruct through-plane aliased low-rank images describing the contrast dynamics occurring because of the transient-state MRF acquisition. T 1 and T 2 times from accelerated acquisitions were compared with those from unaccelerated linear reconstructions in a standardized system phantom and within in vivo brain and prostate experiments on a hybrid 0.35T MRI/linear accelerator., Results: No significant differences between T 1 and T 2 times for the accelerated reconstructions were observed compared to fully sampled acquisitions (p = 0.41 and p = 0.36, respectively). The mean absolute errors in T 1 and T 2 were 5.6% and 2.9%, respectively, between the full and accelerated acquisitions. The SDs in T 1 and T 2 decreased with the advanced accelerated reconstruction compared with the unaccelerated reconstruction (p = 0.02 and p = 0.03, respectively). The quality of the T 1 and T 2 maps generated with the proposed approach are comparable to those obtained using the unaccelerated data sets., Conclusions: Through-plane accelerated MRF with radial k-space coverage was demonstrated at a low field strength of 0.35 T. This method enabled 3D T 1 and T 2 mapping at 0.35 T with a 3-min scan., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

MRI can help to categorize tissues as malignant or non-malignant both anatomically and functionally, with a high level of spatial and temporal resolution. This non-invasive imaging modality has been integrated with radiotherapy in devices that can differentially target the most aggressive and resistant regions of tumours. The past decade has seen the clinical deployment of treatment devices that combine imaging with targeted irradiation, making the aspiration of integrated MRI-guided radiotherapy (MRIgRT) a reality. The two main clinical drivers for the adoption of MRIgRT are the ability to image anatomical changes that occur before and during treatment in order to adapt the treatment approach, and to image and target the biological features of each tumour. Using motion management and biological targeting, the radiation dose delivered to the tumour can be adjusted during treatment to improve the probability of tumour control, while simultaneously reducing the radiation delivered to non-malignant tissues, thereby reducing the risk of treatment-related toxicities. The benefits of this approach are expected to increase survival and quality of life. In this Review, we describe the current state of MRIgRT, and the opportunities and challenges of this new radiotherapy approach., (© 2022. Springer Nature Limited.)

Purpose: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease., Methods: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated., Results: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified., Conclusions: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation., (Published by Elsevier Inc.)

Artificial intelligence (AI) has great potential to transform the clinical workflow of radiotherapy. Since the introduction of deep neural networks, many AI-based methods have been proposed to address challenges in different aspects of radiotherapy. Commercial vendors have started to release AI-based tools that can be readily integrated to the established clinical workflow. To show the recent progress in AI-aided radiotherapy, we have reviewed AI-based studies in five major aspects of radiotherapy including image reconstruction, image registration, image segmentation, image synthesis, and automatic treatment planning. In each section, we summarized and categorized the recently published methods, followed by a discussion of the challenges, concerns, and future development. Given the rapid development of AI-aided radiotherapy, the efficiency and effectiveness of radiotherapy in the future could be substantially improved through intelligent automation of various aspects of radiotherapy.

Purpose: Patient tolerability of magnetic resonance (MR)-guided radiation treatment delivery is limited by the need for repeated deep inspiratory breath holds (DIBHs). This volunteer study assessed the feasibility of continuous positive airway pressure (CPAP) with and without DIBH for respiratory motion management during radiation treatment with an MR-linear accelerator (MR-linac)., Methods and Materials: MR imaging safety was first addressed by placing the CPAP device in an MR-safe closet and configuring a tube circuit via waveguide to the magnet bore. Reproducibility and linearity of the final configuration were assessed. Six healthy volunteers underwent thoracic imaging in a 0.35T MR-linac, with one free breathing (FB) and 2 DIBH acquisitions being obtained at 5 pressures from 0 to 15 cm-H 2 O. Lung and heart volumes and positions were recorded; repeatability was assessed by comparing 2 consecutive DIBH scans. Blinded reviewers graded images for motion artifact using a 3-point grading scale. Participants completed comfort and perception surveys before and after imaging sessions., Results: Compared with FB alone, FB-10, FB-12, and FB-15 cm H 2 O significantly increased lung volumes (+23%, +34%, +44%; all P <.05) and inferiorly displaced the heart (0.86 cm, 0.96 cm, 1.18 cm; all P < . 05). Lung volumes were significantly greater with DIBH-0 cm H 2 O compared with FB-15 cm H 2 O (+105% vs +44%, P  = .01), and DIBH-15 cm H 2 O yielded additional volume increase (+131% vs +105%, P  = .01). Adding CPAP to DIBH decreased lung volume differences between consecutive breath holds (correlation coefficient 0.97 at 15 cm H 2 O vs 0.00 at 0 cm H 2 O). The addition of 15 cm H 2 O CPAP reduced artifact scores ( P  = .03) compared with FB; all DIBH images (0-15 cm H 2 O) had less artifact ( P < .01)., Conclusions: This work demonstrates the feasibility of integrating CPAP in an MR-linac environment in healthy volunteers. Extending this work to a larger patient cohort is warranted to further establish the role of CPAP as an alternative and concurrent approach to DIBH in MR-guided radiation therapy., (© 2022 The Authors.)

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART., (© 2021 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design., Methods and Materials: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts., Results: Paired t tests revealed reasonable maintenance of geometric and anatomic properties ( P < .05 for 4/39 volume comparisons). Maximum displacements >5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery D mean varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations <0.5 Gy)., Conclusions: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality., (© 2021 The Authors.)

Purpose: The acquisition of multiparametric quantitative magnetic resonance imaging (qMRI) is becoming increasingly important for functional characterization of cancer prior to- and throughout the course of radiation therapy. The feasibility of a qMRI method known as magnetic resonance fingerprinting (MRF) for rapid T 1 and T 2 mapping was assessed on a low-field MR-linac system., Methods: A three-dimensional MRF sequence was implemented on a 0.35T MR-guided radiotherapy system. MRF-derived measurements of T 1 and T 2 were compared to those obtained with gold standard single spin echo methods, and the impacts of the radiofrequency field homogeneity and scan times ranging between 6 and 48 min were analyzed by acquiring between 1 and 8 spokes per time point in a standard quantitative system phantom. The short-term repeatability of MRF was assessed over three measurements taken over a 10-h period. To evaluate transferability, MRF measurements were acquired on two additional MR-guided radiotherapy systems. Preliminary human volunteer studies were performed., Results: The phantom benchmarking studies showed that MRF is capable of mapping T 1 and T 2 values within 8% and 10% of gold standard measures, respectively, at 0.35T. The coefficient of variation of T 1 and T 2 estimates over three repeated scans was < 5% over a broad range of relaxation times. The T 1 and T 2 times derived using a single-spoke MRF acquisition across three scanners were near unity and mean percent errors in T 1 and T 2 estimates using the same phantom were < 3%. The mean percent differences in T 1 and T 2 as a result of truncating the scan time to 6 min over the large range of relaxation times in the system phantom were 0.65% and 4.05%, respectively., Conclusions: The technical feasibility and accuracy of MRF on a low-field MR-guided radiation therapy device has been demonstrated. MRF can be used to measure accurate T 1 and T 2 maps in three dimensions from a brief 6-min scan, offering strong potential for efficient and reproducible qMRI for future clinical trials in functional plan adaptation and tumor/normal tissue response assessment., (© 2021 American Association of Physicists in Medicine.)

The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The use of dedicated magnetic resonance simulation (MR-SIM) platforms in Radiation Oncology has expanded rapidly, introducing new equipment and functionality with the overall goal of improving the accuracy of radiation treatment planning. However, this emerging technology presents a new set of challenges that need to be addressed for safe and effective MR-SIM implementation. The major objectives of this report are to provide recommendations for commercially available MR simulators, including initial equipment selection, siting, acceptance testing, quality assurance, optimization of dedicated radiation therapy specific MR-SIM workflows, patient-specific considerations, safety, and staffing. Major contributions include guidance on motion and distortion management as well as MRI coil configurations to accommodate patients immobilized in the treatment position. Examples of optimized protocols and checklists for QA programs are provided. While the recommendations provided here are minimum requirements, emerging areas and unmet needs are also highlighted for future development., (© 2021 American Association of Physicists in Medicine.)

Purpose: Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI)., Methods: Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17-25 s breath-hold (resolution 1.5 × 1.5 × 3 mm 3 ). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated., Results: Across substructures, inter-fraction displacements for 14% in the left-right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were > 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted > 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left-right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (> 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left-right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins., Conclusions: This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The submitting author holds research agreements with Philips Healthcare. Research reported in this publication was partially supported by the National Cancer Institute of the National Institutes of Health under award Number R01 CA204189-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (© 2021 The Authors.)

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To evaluate the dosimetric and image-guided radiation therapy (IGRT) performance of a novel generative adversarial network (GAN) generated synthetic CT (synCT) in the brain and compare its performance for clinical use including conventional brain radiotherapy, cranial stereotactic radiosurgery (SRS), planar, and volumetric IGRT., Methods and Materials: SynCT images for 12 brain cancer patients (6 SRS, 6 conventional) were generated from T1-weighted postgadolinium magnetic resonance (MR) images by applying a GAN model with a residual network (ResNet) generator and a convolutional neural network (CNN) with 5 convolutional layers as the discriminator that classified input images as real or synthetic. Following rigid registration, clinical structures and treatment plans derived from simulation CT (simCT) images were transferred to synCTs. Dose was recalculated for 15 simCT/synCT plan pairs using fixed monitor units. Two-dimensional (2D) gamma analysis (2%/2 mm, 1%/1 mm) was performed to compare dose distributions at isocenter. Dose-volume histogram (DVH) metrics (D 95% , D 99% , D 0.2cc, and D 0.035cc ) were assessed for the targets and organ at risks (OARs). IGRT performance was evaluated via volumetric registration between cone beam CT (CBCT) to synCT/simCT and planar registration between KV images to synCT/simCT digital reconstructed radiographs (DRRs)., Results: Average gamma passing rates at 1%/1mm and 2%/2mm were 99.0 ± 1.5% and 99.9 ± 0.2%, respectively. Excellent agreement in DVH metrics was observed (mean difference ≤0.10 ± 0.04 Gy for targets, 0.13 ± 0.04 Gy for OARs). The population averaged mean difference in CBCT-synCT registrations were <0.2 mm and 0.1 degree different from simCT-based registrations. The mean difference between kV-synCT DRR and kV-simCT DRR registrations was <0.5 mm with no statistically significant differences observed (P > 0.05). An outlier with a large resection cavity exhibited the worst-case scenario., Conclusion: Brain GAN synCTs demonstrated excellent performance for dosimetric and IGRT endpoints, offering potential use in high precision brain cancer therapy., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs., Methods: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches., Results: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA 0.03cc (0.0-63.9% and 0.0 to 17.3 Gy, respectively). LV 0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D 0.03cc . One patient exhibited >10 Gy reduction in D 0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions., Conclusions: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Magnetic resonance-guided radiation therapy (MRgRT) has shown great promise for localization and real-time tumor monitoring. However, to date, quantitative imaging has been limited for low field MRgRT. This work benchmarks quantitative T1, R2*, and Proton Density (PD)mapping in a phantom on a 0.35 T MR-linac and implements a novel acquisition method, STrategically Acquired Gradient Echo (STAGE). To further validate STAGE in a clinical setting, a pilot study was undertaken in a cohort of brain tumor patients to elucidate opportunities for longitudinal functional imaging with an MR-linac in the brain., Methods: STAGE (two triple-echo gradient echo (GRE) acquisitions) was optimized for a 0.35T low-field MR-linac. Simulations were performed to choose two flip angles to optimize signal-to-noise ratio (SNR) and T1-mapping precision. Tradeoffs between SNR, scan time, and spatial resolution for whole-brain coverage were evaluated in healthy volunteers. Data were inputted into a STAGE processing pipeline to yield four qualitative images (T1-weighted, enhanced T1-weighted, proton-density (PD) weighted, and simulated FLuid-Attenuated Inversion Recovery (sFLAIR)), and three quantitative datasets (T1, PD, and R2*). A benchmarking ISMRM/NIST phantom consisting of vials with variable NiCl 2 and MnCl 2 concentrations was scanned using variable flip angles (VFA) (2-60 degrees) and inversion recovery (IR) methods at 0.35 T. STAGE and VFA T1 values of vials were compared to IR T1 values. As measures of agreement with reference values and repeatability, relative error (RE) and coefficient of variability (CV) were calculated, respectively, for quantitative MR values within the phantom vials (spheres). To demonstrate feasibility, longitudinal STAGE data (pretreatment, weekly, and ~ 2 months post-treatment) were acquired in an IRB-approved pilot study of brain tumor cases via the generation of temporal and differential quantitative MRI maps., Results: In the phantom, RE of measured VFA T1 and STAGE relative to IR reference values were 7.0 ± 2.5% and 9.5 ± 2.2% respectively. RE for the PD vials was 8.1 ± 6.8% and CV for phantom R2* measurements was 10.1 ± 9.9%. Simulations and volunteer experiments yielded final STAGE parameters of FA = 50°/10°, 1 × 1 × 3 mm 3 resolution, TR = 40 ms, TE = 5/20/34 ms in 10 min (64 slices). In the pilot study of brain tumor patients, differential maps for R2* and T1 maps were sensitive to local tumor changes and appeared similar to 3 T follow-up MRI datasets., Conclusion: Quantitative T1, R2*, and PD mapping are promising at 0.35 T agreeing well with reference data. STAGE phantom data offer quantitative representations comparable to traditional methods in a fraction of the acquisition time. Initial feasibility of implementing STAGE at 0.35 T in a patient brain tumor cohort suggests that detectable changes can be observed over time. With confirmation in a larger cohort, results may be implemented to identify areas of recurrence and facilitate adaptive radiation therapy., (© 2020 American Association of Physicists in Medicine.)

Recently, interest in MR-only treatment planning using synthetic CTs (synCTs) has grown rapidly in radiation therapy. However, developing class solutions for medical images that contain atypical anatomy remains a major limitation. In this paper, we propose a novel spatial attention-guided generative adversarial network (attention-GAN) model to generate accurate synCTs using T1-weighted MRI images as the input to address atypical anatomy. Experimental results on fifteen brain cancer patients show that attention-GAN outperformed existing synCT models and achieved an average MAE of 85.223±12.08, 232.41±60.86, 246.38±42.67 Hounsfield units between synCT and CT-SIM across the entire head, bone and air regions, respectively. Qualitative analysis shows that attention-GAN has the ability to use spatially focused areas to better handle outliers, areas with complex anatomy or post-surgical regions, and thus offer strong potential for supporting near real-time MR-only treatment planning.

Purpose: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI's soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input., Materials/methods: Thirty-two left-sided whole-breast cancer patients underwent cardiac T2 MRI and CT-simulation. A rigid cardiac-confined MR/CT registration enabled ground truth delineations of 12 substructures (chambers, great vessels (GVs), coronary arteries (CAs), etc.). Paired MRI/CT data (25 patients) were placed into separate image channels to train a three-dimensional (3D) neural network using the entire 3D image. Deep supervision and a Dice-weighted multi-class loss function were applied. Results were assessed pre/post augmentation and post-processing (3D conditional random field (CRF)). Results for 11 test CTs (seven unique patients) were compared to ground truth and a multi-atlas method (MA) via Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Wilcoxon signed-ranks tests. Three physicians evaluated clinical acceptance via consensus scoring (5-point scale)., Results: The model stabilized in ~19 h (200 epochs, training error <0.001). Augmentation and CRF increased DSC 5.0 ± 7.9% and 1.2 ± 2.5%, across substructures, respectively. DL provided accurate segmentations for chambers (DSC = 0.88 ± 0.03), GVs (DSC = 0.85 ± 0.03), and pulmonary veins (DSC = 0.77 ± 0.04). Combined DSC for CAs was 0.50 ± 0.14. MDA across substructures was <2.0 mm (GV MDA = 1.24 ± 0.31 mm). No substructures had statistical volume differences (P > 0.05) to ground truth. In four cases, DL yielded left main CA contours, whereas MA segmentation failed, and provided improved consensus scores in 44/60 comparisons to MA. DL provided clinically acceptable segmentations for all graded patients for 3/4 chambers. DL contour generation took ~14 s per patient., Conclusions: These promising results suggest DL poses major efficiency and accuracy gains for cardiac substructure segmentation offering high potential for rapid implementation into RTP for improved cardiac sparing., (© 2019 American Association of Physicists in Medicine.)

Background Stereotactic body radiation therapy (SBRT) is a proven and effective modality for treatment of hepatic primary and metastatic tumors. However, these lesions are challenging for planning and treatment execution due to natural anatomic changes associated with respiration. Magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution and the ability for real-time image-guided treatment delivery and lesion tracking. Objective To evaluate the plan quality, treatment delivery, and tumor response of a set of liver SBRT cancer treatments delivered with magnetic resonance (MR)-guided radiotherapy on a MR-linear accelerator (MR-linac). Methods Treatment data from 29 consecutive patients treated with SBRT were reviewed. All treatments were performed using a step and shoot technique to one or more liver lesions on an MR-linac platform. Patients received 45 to 50 Gy prescribed to at least 95% of the planning target volume (PTV) in five fractions except for two patients who received 27-30 Gy in three fractions. Computed tomography and MRI simulation were performed in the supine position prior to treatment in the free-breathing, end exhalation, and end inhalation breath-hold positions to determine patient tolerability and potential dosimetric advantages of each technique. Immobilization consisted of using anterior and posterior torso MRI receive coils embedded in a medium-sized vacuum cushion. Gating was performed using sagittal cine images acquired at 4 frames/second. Gating boundaries were defined in the three major axes to be 0.3 to 0.5 cm. An overlapping region of interest, defined as the percentage volume allowed outside the boundary for beam-on to occur, was set between 1 and 10%. The contoured target was assigned a 5-mm PTV expansion. Organs at risk constraints adopted by the American Association of Physicists in Medicine Task Group 101 were used during optimization. Results Twenty-nine patients, with a total of 34 lesions, successfully completed the prescribed treatment with minimal treatment breaks or delays. Twenty-one patients were treated at end-exhale, and six were treated at end-inhale. Two patients were treated using a free-breathing technique due to poor compliance with breath-hold instructions. The reported mean liver dose was 5.56 Gy (1.39 - 10.43; STD 2.85) and the reported mean liver volume receiving the prescribed threshold dose was 103.1 cm 3  (2.9 - 236.6; STD 75.2). Follow-up imaging at one to 12 months post treatment confirmed either stable or decreased size of treated lesions in all but one patient. Toxicities were mild and included nausea/vomiting, abdominal pain and one case of bloody diarrhea. Four patients died due to complications from liver cirrhosis unrelated to radiation effect. Conclusion SBRT treatment using a gated technique on an MR-linac has been successfully demonstrated. Potential benefits of this modality include decreased liver dose leading to decreased toxicities. Further studies to identify the benefits and risks associated with MR-guided SBRT are necessary., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2019, Feldman et al.)

Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP). Images were created from raw projection data for 11 prostate cancer cases using FBP and nine different MBIR reconstructions (3 protocols/3 noise reduction levels) yielding 10 reconstructions/patient. Five bony structures, bladder, rectum, prostate, and seminal vesicles (SVs) were segmented using an auto-segmentation pipeline that renders 3D binary masks for analysis. Performance was evaluated for volume percent difference (VPD) and Dice similarity coefficient (DSC), using FBP as the gold standard. Nonparametric Friedman tests plus post hoc all pairwise comparisons were employed to test for significant differences (P < 0.05) for soft tissue organs and protocol/level combinations. A physician performed qualitative grading of 396 MBIR contours across the prostate, bladder, SVs, and rectum in comparison to FBP using a six-point scale. MBIR contours agreed with FBP for bony anatomy (DSC ≥ 0.98), bladder (DSC ≥ 0.94, VPD < 8.5%), and prostate (DSC = 0.94 ± 0.03, VPD = 4.50 ± 4.77% (range: 0.07-26.39%). Increased variability was observed for rectum (VPD = 7.50 ± 7.56% and DSC = 0.90 ± 0.08) and SVs (VPD and DSC of 8.23 ± 9.86% range (0.00-35.80%) and 0.87 ± 0.11, respectively). Over the all protocol/level comparisons, a significant difference was observed for the prostate VPD between BSPL1 and BSTL2 (adjusted P-value = 0.039). Nevertheless, 300 of 396 (75.8%) of the four soft tissue structures using MBIR were graded as equivalent or better than FBP, suggesting that MBIR offered potential improvements in auto-segmentation performance when compared to FBP. Future work may involve tuning organ-specific MBIR parameters to further improve auto-segmentation performance. Running title: Impact of CT Reconstruction Algorithm on Auto-segmentation Performance., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

While MRI-only radiation treatment planning (RTP) is becoming more widespread, a robust clinical solution for patient-specific distortion corrections is not available. This work explores B 0 mapping based on mDIXON imaging, often performed for MR-only RTP, as an alternative to separate dual-acquisition gradient-recalled echo imaging, with the overarching goal of developing an efficient and robust approach for patient-specific distortion correction. Initial benchmarking was conducted by scanning a phantom and generating B 0 field maps with two approaches: (1) conventional B 0 mapping and (2) experimental mDIXON imaging. Distortion maps were derived from the field maps and compared. The head and neck regions, including brain, of ten healthy volunteers were then evaluated at 1.5 T and 3 T. Distortion maps were again compared between approaches, using difference maps and histogram analysis. Overall, conventional B 0 mapping was well approximated by mDIXON imaging: The distortions of 95% of the voxels in the phantom estimated by mDIXON and conventional B 0 mapping differed by  <0.02 mm (1.5 T) and  <0.04 mm (3 T), while the 95-percentiles of the distortions estimated by conventional B 0 mapping were  <0.06 mm (1.5 T) and  <0.12 mm (3 T). In head and neck the distortions of 99% of the voxels were within  ±0.2 mm at 1.5 T for both approaches and within  ±0.4 mm and  ±0.5 mm at 3 T for mDIXON imaging and conventional B 0 mapping, respectively. The majority of differences in vivo were confined to regions with high spatial variation of the B 0 field, mostly around internal air cavities. For 1.5 T, the mDIXON imaging-based correction alone reduced the 95-percentile of distortions from 0.15 mm to 0.03 mm and within the brain from 0.06 mm to 0.02 mm. Slightly lower reductions were observed at 3 T. In conclusion, mDIXON imaging closely approximated conventional B 0 mapping for patient-specific distortion assessment. Estimates in the brain were in good agreement, and slight differences were observed near air/tissue interfaces in the head and neck. Overall, mDIXON imaging-based B 0 field maps may be advantageous for rapid patient-specific distortion correction without additional imaging.

Purpose: MR-guided radiation therapy (RT) offers unparalleled soft tissue contrast for localization and target tracking. However, MRI distortions may be detrimental to high precision RT. This work characterizes the gradient nonlinearity (GNL) and total distortions over the first year of clinical operation of a 0.35T MR-linac., Methods: For GNL characterization, an in-house large field of view (FOV) phantom (60 × 42.5 × 55 cm 3 , >6000 spherical landmarks) was configured and scanned at four timepoints with forward/reverse read polarities (Gradient Echo sequence, FA/TR/TE = 28°/30 ms/6 ms). GNL was measured in Anterior-Posterior (AP), Left-Right (LR), and Superior-Inferior (SI) frequency-encoding directions based on deviation of the auto-segmented landmark centroids between rigidly registered MR and CT images and assessed based on radial distance from magnet isocenter. Total distortion was assessed using a 30 × 30 cm 2 grid phantom oriented along the cardinal axes over >1 year of operation., Results: The scanner's spatial integrity within the first ~10 months was stable (maximum total distortion variation = 10/6/8%, maximum distortion = 1.41/0.99/1.56 mm in Axial/Coronal/Sagittal planes, respectively). GNL distortions measured during this time period <10 cm from isocenter were (-0.74, 0.45), (-0.67, 0.53), and (-0.86, 0.70) mm in AP/LR/SI directions. In the 10-20 cm range, <1.5% of the distortions exceeded 2 mm in the AP and LR axes while <4% of the distortions exceeded 2 mm for SI. After major repairs and magnet re-shim, detectable changes were observed in total and GNL distortions (20% reduction in AP and 36% increase in SI direction in the 20-25 cm range). Across all timepoints and axes, 38-53% of landmarks in the 20-25 cm range were displaced by >1 mm., Conclusions: GNL distortions were negligible within a 10 cm radius from isocenter. However, in the periphery, non-negligible distortions of up to ~7 mm were observed, which may necessitate GNL corrections for MR-IGRT for treatment sites distant from magnet isocenter., (© 2019 American Association of Physicists in Medicine.)

Purpose: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions., Materials and Methods: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state., Results: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%)., Conclusions: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. Because cardiac substructures are poorly visualized on treatment-planning computed tomography (CT) scans, we used the superior soft-tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT., Methods and Materials: Thirty-one patients with left-sided breast cancer underwent a T2-weighted MR imaging scan and noncontrast simulation CT scans. A radiation oncologist delineated 13 substructures (chambers, great vessels, coronary arteries, etc) using MR/CT information via cardiac-confined rigid registration. Ground-truth contours for 20 patients were inputted into an intensity-based deformable registration atlas and applied to 11 validation patients. Automatic segmentations involved using majority vote and Simultaneous Truth and Performance Level Estimation (STAPLE) strategies with 1 to 15 atlas matches. Performance was evaluated via Dice similarity coefficient (DSC), mean distance to agreement, and centroid displacement. Three physicians evaluated segmentation performance via consensus scoring by using a 5-point scale. Dosimetric assessment included measurements of mean heart dose, left ventricular volume receiving 5 Gy, and left anterior descending artery mean and maximum doses., Results: Atlas approaches performed similarly well, with 7 of 13 substructures (heart, chambers, ascending aorta, and pulmonary artery) having DSC >0.75 when averaged over 11 validation patients. Coronary artery segmentations were not successful with the atlas-based approach (mean DSC <0.3). The STAPLE method with 10 matches yielded the highest DSC and the lowest mean distance to agreement for all high-performing substructures (omitting coronary arteries). For the STAPLE method with 10 matches, >50% of all validation contours had centroid displacements <3.0 mm, with the largest shifts in the coronary arteries. Atlas-generated contours had no statistical difference from ground truth for left anterior descending artery maximum dose, mean heart dose, and left ventricular volume receiving 5 Gy (P > .05). Qualitative contour grading showed that 8 substructures required minor modifications., Conclusions: The hybrid MR/CT atlas provided reliable segmentations of chambers, heart, and great vessels for patients undergoing noncontrast CT, suggesting potential widespread applicability for routine treatment planning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

MR-only treatment planning and MR-IGRT leverage MRI's powerful soft tissue contrast for high-precision radiation therapy. However, anthropomorphic MR-compatible phantoms are currently limited. This work describes the development and evaluation of a custom-designed, modular, pelvic end-to-end (PETE) MR-compatible phantom to benchmark MR-only and MR-IGRT workflows. For construction considerations, subject data were assessed for phantom/skeletal geometry and internal organ kinematics to simulate average male pelvis anatomy. Various materials for the bone, bladder, and rectum were evaluated for utility within the phantom. Once constructed, PETE underwent CT-SIM, MR-Linac, and MR-SIM imaging to qualitatively assess organ visibility. Scans were acquired with various bladder and rectal volumes to assess component interactions, filling capabilities, and filling reproducibility via volume and centroid differences. PETE simulates average male pelvis anatomy and comprises an acrylic body oval (height/width = 23.0/38.1 cm) and a cast-mold urethane skeleton, with silicone balloons simulating bladder and rectum, a silicone sponge prostate, and hydrophilic poly(vinyl alcohol) foam to simulate fat/tissue separation between organs. Access ports enable retrofitting the phantom with other inserts including point/film-based dosimetry options. Acceptable contrast was achievable in CT-SIM and MR-Linac images. However, the bladder was challenging to distinguish from background in CT-SIM. The desired contrast for T1-weighted and T2-weighted MR-SIM (dark and bright bladders, respectively) was achieved. Rectum and bone exhibited no MR signal. Inputted volumes differed by <5 and <10 mL from delineated rectum (CT-SIM) and bladder (MR-SIM) volumes. Increasing bladder and rectal volumes induced organ displacements and shape variations. Reproduced volumes differed by <4.5 mL, with centroid displacements <1.4 mm. A point dose measurement with an MR-compatible ion chamber in an MR-Linac was within 1.5% of expected. A novel, modular phantom was developed with suitable materials and properties that accurately and reproducibly simulate status changes with multiple dosimetry options. Future work includes integrating more realistic organ models to further expand phantom options., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: This work characterizes a novel exponential 4DCT reconstruction algorithm (EXPO), in phantom and patient, to determine its impact on image quality as compared to the standard cosine-squared weighted 4DCT reconstruction., Methods: A motion platform translated objects in the superior-inferior (S-I) direction at varied breathing rates (8-20 bpm) and couch pitches (0.06-0.1) to evaluate interplay between parameters. Ten-phase 4DCTs were acquired and data were reconstructed with cosine squared and EXPO weighting. To quantify the magnitude of image blur, objects were translated in the anterior-posterior (A-P) and S-I directions for full-width half maximum (FWHM) analysis between both 4DCT algorithms and a static case. 4DCT sinogram data for 10 patients were retrospectively reconstructed using both weighting factors. Image subtractions elucidated intensity and boundary differences. Subjective image quality grading (presence of image artifacts, noise, spatial resolution (i.e., lung/liver boundary sharpness), and overall image quality) was conducted yielding 200 evaluations., Results: After taking static object size into account, the FWHM of EXPO reconstructions in the A-P direction was 3.3 ± 1.7 mm (range: 0-4.9) as compared to cosine squared 9.8 ± 4.0 mm (range: 2.6-14.4). The FWHM of objects translated in the S-I direction reconstructed with EXPO agreed better with the static FWHM than the cosine-squared reconstructions. Slower breathing periods, faster couch pitches, and intermediate 4DCT phases had the largest reductions of blurring with EXPO. 18 of 60 comparisons of artifacts were improved with EXPO reconstruction, whereas no appreciable changes were observed in image quality scores. In 18 of 20 cases, EXPO provided sharper images although the reduced projections also increased baseline noise., Conclusion: Exponential weighted 4DCT offers potential for reducing image blur (i.e., improving image sharpness) in 4DCT with a tendency to reduce artifacts. Future work will involve evaluating the impact on treatment planning including delineation ability and dose calculation., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To evaluate the implementation of a magnetic resonance (MR)-only workflow (ie, implementing MR simulation as the primary planning modality) using failure mode and effects analysis (FMEA) in comparison with a conventional multimodality (MR simulation in conjunction with computed tomography simulation) workflow for pelvis external beam planning., Methods and Materials: To perform the FMEA, a multidisciplinary 9-member team was assembled and developed process maps, identified potential failure modes (FMs), and assigned numerical values to the severity (S), frequency of occurrence (O), and detectability (D) of those FMs. Risk priority numbers (RPNs) were calculated via the product of S, O, and D as a metric for evaluating relative patient risk. An alternative 3-digit composite number (SOD) was computed to emphasize high-severity FMs. Fault tree analysis identified the causality chain leading to the highest-severity FM., Results: Seven processes were identified, 3 of which were shared between workflows. Image fusion and target delineation subprocesses using the conventional workflow added 9 and 10 FMs, respectively, with 6 RPNs >100. By contrast, synthetic computed tomography generation introduced 3 major subprocesses and propagated 46 unique FMs, 15 with RPNs >100. For the conventional workflow, the largest RPN scores were introduced by image fusion (RPN range, 120-192). For the MR-only workflow, the highest RPN scores were from inaccuracies in target delineation resulting from misinterpretation of MR images (RPN = 240) and insufficient management of patient- and system-level distortions (RPN = 210 and 168, respectively). Underestimation (RPN = 140) or overestimation (RPN = 192) of bone volume produced higher RPN scores. The highest SODs for both workflows were related to changes in target location because of internal anatomy changes (conventional = 961, MR-only = 822)., Conclusions: FMEA identified areas for mitigating risk in MR-only pelvis RTP, and SODs identified high-severity process modes. Efforts to develop a quality management program to mitigate high FMs are underway.

Purpose: Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT., Methods and Materials: Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)-2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed., Results: DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (P < .05). The population average absolute shifts were 0.77 ± 0.58 and 0.76 ± 0.59 mm for CT and synCT, respectively, for all axes/quadrants. Three-dimensional vectors were <2 mm in 77.7 ± 10.8% and 76.5 ± 7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in postsurgical cases (vector displacements >2 mm in affected quadrants)., Conclusions: DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Organ-at-risk (OAR) segmentation is a key step for radiotherapy treatment planning. Model-based segmentation (MBS) has been successfully used for the fully automatic segmentation of anatomical structures and it has proven to be robust to noise due to its incorporated shape prior knowledge. In this work, we investigate the advantages of combining neural networks with the prior anatomical shape knowledge of the model-based segmentation of organs-at-risk for brain radiotherapy (RT) on Magnetic Resonance Imaging (MRI). We train our boundary detectors using two different approaches: classic strong gradients as described in [4] and as a locally adaptive regression task, where for each triangle a convolutional neural network (CNN) was trained to estimate the distances between the mesh triangles and organ boundary, which were then combined into a single network, as described by [1]. We evaluate both methods using a 5-fold cross- validation on both T1w and T2w brain MRI data from sixteen primary and metastatic brain cancer patients (some post-surgical). Using CNN-based boundary detectors improved the results for all structures in both T1w and T2w data. The improvements were statistically significant ( p < 0.05) for all segmented structures in the T1w images and only for the auditory system in the T2w images.

Background: Patient-specific distortions, particularly near tissue/air interfaces, require assessment for magnetic resonance (MR) only radiation treatment planning (RTP). However, patients are dynamic due to changes in physiological status during imaging sessions. This work investigated changes in subject-induced susceptibility distortions to pelvic organs at different bladder states to support pelvis MR-only RTP., Methods: Pelvises of 9 healthy male volunteers were imaged at 1.0 Tesla (T), 1.5 T, and 3.0 T. Subject-induced susceptibility distortion field maps were generated using a dual-echo gradient-recalled echo (GRE) sequence with B 0 field maps obtained from the phase difference between the two echoes acquired at several bladder volume states (3-4/subject, 32 overall). T2 turbo spin echo images were also acquired at each bladder state for organ delineation. Magnet central frequency was tracked over time. Distortion map differences and boxplots were computed to characterize changes within the clinical target volume (CTV), bladder, seminal vesicles, and prostate volumes., Results: The time between the initial and final B0 maps was 42.6 ± 13.9 (range: 13.2-62.1) minutes with minimal change in magnet central frequency (0.02 ± 0.05 mm (range: - 0.06 - 0.12 mm)). Subject-induced susceptibility distortion across all bladder states, field strengths, and subjects was relatively small (1.4-1.9% of all voxels in the prostate and seminal vesicles were distorted > 0.5 mm). In the bladder, no voxels exhibited distortions > 1 mm. An extreme case acquired at 3.0 T with a large volume of rectal air yielded 27.4-34.6% of voxels within the CTVs had susceptibility-induced distortions > 0.5 mm across all time points., Conclusions: Our work suggests that subject-induced susceptibility distortions caused by bladder/rectal conditions are generally small and subject-dependent. Local changes may be non-negligible within the CTV, thus proper management of filling status is warranted. Future work evaluating the impact of multiple models to accommodate for extreme status changes may be advantageous.

Purpose: While MR-only treatment planning using synthetic CTs (synCTs) offers potential for streamlining clinical workflow, a need exists for an efficient and automated synCT generation in the brain to facilitate near real-time MR-only planning. This work describes a novel method for generating brain synCTs based on generative adversarial networks (GANs), a deep learning model that trains two competing networks simultaneously, and compares it to a deep convolutional neural network (CNN)., Methods: Post-Gadolinium T1-Weighted and CT-SIM images from fifteen brain cancer patients were retrospectively analyzed. The GAN model was developed to generate synCTs using T1-weighted MRI images as the input using a residual network (ResNet) as the generator. The discriminator is a CNN with five convolutional layers that classified the input image as real or synthetic. Fivefold cross-validation was performed to validate our model. GAN performance was compared to CNN based on mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) metrics between the synCT and CT images., Results: GAN training took ~11 h with a new case testing time of 5.7 ± 0.6 s. For GAN, MAEs between synCT and CT-SIM were 89.3 ± 10.3 Hounsfield units (HU) and 41.9 ± 8.6 HU across the entire FOV and tissues, respectively. However, MAE in the bone and air was, on average, ~240-255 HU. By comparison, the CNN model had an average full FOV MAE of 102.4 ± 11.1 HU. For GAN, the mean PSNR was 26.6 ± 1.2 and SSIM was 0.83 ± 0.03. GAN synCTs preserved details better than CNN, and regions of abnormal anatomy were well represented on GAN synCTs., Conclusions: We developed and validated a GAN model using a single T1-weighted MR image as the input that generates robust, high quality synCTs in seconds. Our method offers strong potential for supporting near real-time MR-only treatment planning in the brain., (© 2018 American Association of Physicists in Medicine.)

Introduction: The purpose of this study was to investigate the systematic localization accuracy, treatment planning capability, and delivery accuracy of an integrated magnetic resonance imaging guided Linear Accelerator (MR-Linac) platform for stereotactic radiosurgery., Materials and Methods: The phantom for the end-to-end test comprises three different compartments: a rectangular MR/CT target phantom, a Winston-Lutz cube, and a rectangular MR/CT isocenter phantom. Hidden target tests were performed at gantry angles of 0, 90, 180, and 270 degrees to quantify the systematic accuracy. Five patient plans with a total of eleven lesions were used to evaluate the dosimetric accuracy. Single-isocenter IMRT treatment plans using 10-15 coplanar beams were generated to treat the multiple metastases., Results: The end-to-end localization accuracy of the system was 1.0 ± 0.1 mm. The conformity index, homogeneity index and gradient index of the plans were 1.26 ± 0.22, 1.22 ± 0.10, and 5.38 ± 1.44, respectively. The average absolute point dose difference between measured and calculated dose was 1.64 ± 1.90%, and the mean percentage of points passing the 3%/1 mm gamma criteria was 96.87%., Conclusions: Our experience demonstrates that excellent plan quality and delivery accuracy was achievable on the MR-Linac for treating multiple brain metastases with a single isocenter., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation., Methods: Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose., Results: Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20-2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100-500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz., Conclusion: Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the downstream trachea, can generate audible sound levels.

Over the past decade, the application of magnetic resonance imaging (MRI) has increased, and there is growing evidence to suggest that improvements in the accuracy of target delineation in MRI-guided radiation therapy may improve clinical outcomes in a variety of cancer types. However, some considerations should be recognized including patient motion during image acquisition and geometric accuracy of images. Moreover, MR-compatible immobilization devices need to be used when acquiring images in the treatment position while minimizing patient motion during the scan time. Finally, synthetic CT images (i.e. electron density maps) and digitally reconstructed radiograph images should be generated from MRI images for dose calculation and image guidance prior to treatment. A short review of the concepts and techniques that have been developed for implementation of MRI-only workflows in radiation therapy is provided in this document.