ViewRay MRIdian Research Articles

Optimization and validation of low-field MP2RAGE T1 mapping on 0.35T MR-Linac: Toward adaptive dose painting with hypoxia biomarkers.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1-to-noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1-weighted contrast images with simultaneous T1 mapping. To optimize MP2RAGE for low-field T1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T1 mapping in healthy volunteers. The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T1 values (400-850ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (±SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (±SD) T1 values for WM and GM were determined. Whole-brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T1 difference maps were generated to evaluate 3D spatial variation. Low-field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250ms, inversion times (TI1/TI2) of 500/1200ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (±SD) relative error of 3.45%±1.30%, T1NR of 20.13±5.31, and CV of 2.22%±0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (±SD) T1 values: 435.36±10.01ms for WM and 623.29±14.64ms for GM across subjects, showing excellent concordance with literature. Whole-brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46%±0.31% and 0.35%±0.18% for WM and GM, respectively. Voxel-by-voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM. Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers.

MRI-Linac radiation therapy outcomes in patients with prostate, breast and other advanced malignancies.

e13811 Background: MR-guided radiation therapy offers an innovative approach, providing superior soft tissue contrast that enables clinicians to deliver higher doses to the target site with fewer fractions. The objective of the study is to assess objective response rates and adverse effects related to a community-based single-institution experience with the ViewRay MRIdian. Methods: An IRB-approved registrational trial was conducted at the Providence Cancer Institute starting May 2020, with data cutoff of September 2023. All patients treated underwent MR screening, and the target site(s) were treated using hypofractionated radiation therapy in ≤5 fractions. The primary endpoint was to assess adverse effects attributed to radiation therapy. Secondary measures included local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and change in prostate-specific antigen (PSA) for patients treated definitively for prostate cancer. The assessments were performed under the guidance of experienced radiation oncologists. Results: From May 2020 to September 2023, n=257 patients received treatment on the MRIdian with a median follow-up of 430 days [range 4-1221 days]. One and 2-year LRFS was 92% and 87%, and excluding prostate and breast cancer, 83% and 70%. Definitive prostatestereotactic body radiation therapy(SBRT) was delivered to 117 patients and significantly reduced PSA (mean difference -6.27, p<0.0001), with no local failures to date. One and 2-year DMFS was 75% and 67%, though if excluding definitive prostate SBRT and partial breast irradiation, these were 48% and 33%. The OS rate at 1 and 2 years was 86% and 76%. Excluding prostate and breast cancer, the 1 and 2-year OS was 74% and 55%. Grade 3+ adverse events possibly or definitely attributable to radiation therapy were noted in 5% (n=13/257) of patients, including 2 possible treatment-associated deaths (bowel perforation following liver SBRT, and respiratory failure following lung SBRT and trastuzumab-deruxtecan systemic therapy). Conclusions: Our institutional experience with the MRIdian demonstrated high levels of local control, while overall survival was driven by out-of-field failures. Serious adverse events were infrequent, but more common in abdominal targets highlighting the need for careful planning and tight organs at risk (OAR) constraints, particularly if systemic therapy is delivered soon after radiation.

Uncertainty of scintillator-based field-output factor measurements in MR-Linacs with the two-channel chromatic stem removal technique

Current international protocols such as the IAEA/AAPM TRS-483 for small field dosimetry do not include recommendations for measurements in strong magnetic fields as found in MR-Linacs (i.e. megavoltage x-ray radiotherapy units with built-in magnetic resonance imaging). A EURAMET research project was therefore launched to support the traceability of such measurements and to contribute to the metrological basis for future recommendations. Given the high degree of water equivalence and the small size of fiber-coupled plastic scintillators, one objective of the project was to study the suitability of this detector type for dosimetry in MR-Linacs and to demonstrate their use in a clinical environment. This manuscript reports results of that work. A protocol for measuring field output factors with plastic scintillation detectors was developed. The protocol is based on calibration of the scintillators directly in a water phantom positioned in the MR-Linac rather than in a water-equivalent solid phantom as has been a common technique for conventional linacs. A detailed uncertainty budget was established involving all known sources of uncertainty including the systematic influence of light attenuation through the fiber when measuring in different field sizes. The protocol was used to measure field output factors at five MR-Linac's (four Viewray MRIdian's and one Elekta Unity). The protocol showed a high level of robustness leading to a less than 0.3 % deviation between field output factors calculated based on calibration data obtained before or after the field-output factor measurements. The correction for light attenuation was less than 0.4 % for all fields measured but showed a systematic offset, with larger corrections needed for small field sizes.This robustness of the protocol was further demonstrated by the closeness of agreement (agreement within uncertainty) for field-output factor measurements with two different scintillators (BCF-12 and BCF-60) for square fields (size: 0.83 cm × 0.83 cm or larger) in four nominally identical Viewray MRIdian's. To test the accuracy of the scintillator measurements, the system was used for characterization of a PTW 60019 micro diamond detector in a Viewray MRIdian. Scintillator based correction factors for output factor measurements with the micro diamond detector were found to be in agreement with independent Monte-Carlo computations. The study therefore supports that plastic scintillation detectors are an excellent option for measuring field output factors in MR-Linacs.

Characterization of real-time cine MR imaging distortion on 0.35 T MRgRT with concentric cine imaging QA phantom

Objective. Real-time MRgRT uses 2D-cine imaging for target tracking and motion evaluation. Rotation of gantry induced B 0 off-resonance, resulting in image artifacts and imaging isocenter-shift precluding MR-guided arc therapy. Standard MRI phantoms designed for higher resolution images face challenges when low-resolution cine imaging is needed to achieve high frame rates. This work aimed to examine the spatial accuracy including geometric distortion and isocenter shift in real-time during gantry rotation on a 0.35 T MR-Linac using the concentric Cine imaging quality assurance (QA) phantom and its associated image analysis software. Approach. The Cine imaging QA phantom consists of two concentric shells of low-T1 mineral oil and a central alignment structure. The phantom was scanned on three different MRI systems; 0.55 T Siemens Free.Max, 1.5 T Philips Ingenia, and 0.35 T ViewRay MRIdian MR-Linac using 2D balanced steady-state free precession (bSSFP) imaging sequence. In addition, bSSFP cine MRI with the banding artifact correction was tested on 0.35 T ViewRay MR-Linac. Images from the MR-Linac were acquired with the Linac gantry stationary and rotating from gantry 300°→ 0° and vice versa. Three orthogonal image planes were scanned excluding the 1.5 T Philips Ingenia, where only the axial plane was scanned. The image analysis software calculated the distortion values as well as the isocenter position for each cine frame. Main results. The geometric distortion of cine imaging on MRIs and MR-Linac at gantry stationary are within 1 mm while the substantial geometric distortion of 2 and 2.2 mm were observed on 0.35 T MR-Linac while rotating the gantry clockwise (300°→ 0°) and counterclockwise 0°→ 300° respectively. The average imaging isocenter shift was 0.1 mm for both MRIs and the static gantry and imaging isocenter shift of ≤1.5 mm was observed during the gantry rotation. The imaging isocenter shift decreased by 1 ± 0.2 mm clockwise and counterclockwise with B 0 compensation. Significance. The concentric Cine imaging QA phantom and its associated software effectively demonstrate the image distortion on real-time cine imaging on regular MRIs and 0.35 T MR-Linac. The results of significant geometric distortion with a rotating gantry in the MR-Linac system require further investigation to alleviate the extent of the image distortion.

MV-based relative electron density estimation (iMREDe) for MR-LINAC dose calculation.

MR-LINAC systems have been increasingly utilized for real-time imaging in adaptive treatments worldwide. Challenges in MR representation of air cavities and subsequent estimation of electron density maps impede planning efficiency and may lead to dose calculation uncertainties. To demonstrate the generation of accurate electron density maps using the primary MV beam with a flat-panel imager. The ViewRay MRIdian MR-LINAC system was modeled digitally for Monte Carlo simulations. Iron shimming, the magnetic field, and the proposed flat panel detector were included in the model. The effect of the magnetic field on the detector response was investigated. Acquisition of projections over 360 degrees was simulated for digital phantoms of the Catphan 505 phantom and a patient treated for Head and Neck cancer. Shim patterns on the projections were removed and detector noise linearity was assessed. Electron density maps were generated for the digital patient phantom using the flat-panel detector and compared with actual treatment planning CT generated electron density maps of the same patient. The effect of the magnetic field on the detector point-spread function (PSF) was found to be substantial for field strengths above 50 mT. Shims correction in the projection images using air normalization and in-painting effectively removed reconstruction artifacts without affecting noise linearity. The relative difference between reconstructed electron density maps from the proposed method and electron density maps generated from the treatment planning CT was 11% on average along all slices included in the iMREDe reconstruction. The proposed iMREDe technique demonstrated the feasibility of generating accurate electron densities for the ViewRay MRIdian MR-LINAC system with a flat-panel imager and the primary MV beam. This work is a step towards reducing the time and effort required for adaptive radiotherapy in the current ViewRay MR-LINAC systems.

Receive coil quality assurance procedure and automated analysis for ViewRay MRIdian MR-Linac.

Regular receiving coil quality assurance (QA) is required to ensure image quality of an MRIdian Linac system. The manufacturer provides a spherical phantom and positioning tube for single-slice signal-to-noise ratio (SNR) and uniformity assessments. We aimed to improve imaging setup and coverage and eliminate inter-scan variability by employing multi-slice imaging of a stable phantom. Additionally, we strived to expedite analysis by developing objective, automated analysis software. A 5300mL cylindrical plastic bottle placed in plastic bins was scanned at isocenter using a spin-echo sequence with NEMA-recommended parameters and 18 axial slices, avoiding phantom repositioning. Acquisition was repeated with and without prescan normalization filtering and by saving uncombined element images. Obtained data were analyzed using custom open-source MATLAB code. Signal and noise images were automatically assigned, and ROIs for SNR and uniformity calculations were defined using image thresholding. SNR and uniformity pass/fail decisions were made using baseline comparisons. The proposed method was successfully implemented as monthly coil QA for 3.5 years. Setup and scanning took 41 min on average for a coil set. Automated image analysis was completed in a few minutes. Signal intensity peaked around +90 or -90mm for Torso or Head/Neck coil unfiltered images. Noise peaked and minimized SNR inside±30mm from isocenter, while maximizing it around±130mm. Prescan normalization smoothed signal response, reduced SNR and increased uniformity. Individual coil element image analysis identified their position, signal or noise response and SNR. SNR and uniformity pass/fail thresholds were set for already tested and new coils. Conspicuous and subtle Torso coil malfunctions were detected considering baseline deviations of combined and individual element results. Our QA method eliminated observer bias and provided insights into coil function, image filtering performance and coil element location. It provided SNR and uniformity thresholds and identified faulty coil elements.

Experimental determination of magnetic field quality conversion factors for eleven ionization chambers in 1.5 T and 0.35 T MR-linac systems.

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

Dosimetric predictors for genitourinary toxicity in MR-guided stereotactic body radiation therapy (SBRT): Substructure with fraction-wise analysis.

MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients. (1) To identify dosimetric predictors, potentially in combination with clinical parameters, of GU toxicity following SBRT by leveraging MRgRT to accurately monitor daily dose, beyond predicted dose calculated during planning. (2) Improve awareness of toxicity-sensitive bladder substructures, specifically the trigone and urethra. Sixty-nine prostate cancer patients (NCT04384770 clinical trial) were treated on a ViewRay MRIdian MRgRT system, with 40Gy prescribed to 95% of the PTV in over five fractions. Overall, 17 (24.6%) prostate patients reported acute grade 2 GU toxicity. The CTV, PTV, bladder, bladder wall, trigone, urethra, rectum, and rectal wall were contoured on the planning and daily treatment MRIs. Planning and daily treatment DVHs (0.1Gy increments), organ doses (min, max, mean), and organ volumes were recorded. Daily dose was estimated by transferring the planning dose distributions to the daily MRI based on the daily setup alignment. Patients were partitioned into a training (55) and testing set (14). Dose features were pre-filtered using a t-test followed by maximum relevance minimum redundancy (MRMR) algorithm. Logistic regression was investigated with regularization to select dosimetric predictors. Specifically, two approaches: time-group least absolute shrinkage and selection (LASSO), and interactive grouped greedy algorithm (IGA) were investigated. Shared features across the planning and five treatment fractions were grouped to encourage consistency and stability. The conventional flat non-temporally grouped LASSO was also evaluated to provide a solid benchmark. After feature selection, a final logistic regression model was trained. Dosimetric regression models were compared to a clinical regression model with only clinical parameters (age, baseline IPSS, prostate gland size, ADT usage, etc.) and a hybrid model, combining the best performing dosimetric features with the clinical parameters, was evaluated. Final model performance was evaluated on the testing set using accuracy, sensitivity, and specificity determined by the optimal threshold of the training set. IGA had the best testing performance with an accuracy/sensitivity/specificity of 0.79/0.67/0.82, selecting 12 groups covering the bladder (V19.8Gy, V20.5Gy), bladder wall (19.7Gy), trigone (15.9, 18.2, 43.3Gy), urethra (V41.4Gy, V41.7Gy), CTV (V41.9Gy), rectum (V8.5Gy), and rectal wall (1.2, 44.1Gy) dose features. Absolute bladder V19.8Gy and V20.5Gy were the most important features, followed by relative trigone 15.9 and 18.2Gy. Inclusion of clinical parameters in the hybrid model with IGA did not significantly change regression performance. Overall, IGA feature selection resulted in the best GU toxicity prediction performance. This exploratory study demonstrated the feasibility of identification and analysis of dosimetric toxicity predictors with awareness to sensitive substructures and daily dose to potentially provide consistent and stable dosimetric metrics to guide treatment planning. Further patient accruement is warranted to further assess dosimetric predictor and perform validation.

Accumulated dose implications from systematic dose-rate transients in gated treatments with Viewray MRIdian accelerators

The combination of magnetic resonance (MR) imaging and linear accelerators (linacs) into MR-Linacs enables continuous MR imaging and advanced gated treatments of patients. Previously, a dose-rate transient (∼8% reduced dose rate during the initial 0.5 s of each beam) was identified for a Viewray MRIdian MR-Linac (Klavsen et al 2022 Radiation Measurement 106759). Here, the dose-rate transient is studied in more detail at four linacs of the same type at different hospitals. The implications of dose-rate transients were examined for gated treatments. The dose-rate transients were investigated using dose-per pulse measurements with organic plastic scintillators in three experiments: (i) A gated treatment with the scintillator placed in a moving target in a dynamic phantom, (ii) a gated treatment with the same dynamic conditions but with the scintillator placed in a stationary target, and (iii) measurements in a water-equivalent material to examine beam quality deviations at a dose-per-pulse basis. Gated treatments (i) compared with non-gated treatments with a static target in the same setup showed a broadening of accumulated dose profiles due to motion (dose smearing). The linac with the largest dose-rate transient had a reduced accumulated dose of up to (3.1 ± 0.65) % in the center of the PTV due to the combined dose smearing and dose-rate transient effect. Dose-rate transients were found to vary between different machines. Two MR-Linacs showed initial dose-rate transients that could not be identified from conventional linearity tests. The source of the transients includes an initial change in photon fluence rate and an initial change in x-ray beam quality. For gated treatments, this caused a reduction of more than 1% dose delivered at the central part of the beam for the studied, cyclic-motion treatment plan. Quality assurance of this effect should be considered when gated treatment with the Viewray MRIdian is implemented clinically.

PO-1670 Initial Assessment of Adaptive Pancreas SBRT Treatment Efficiency using ViewRay MRIdian A3i

PO-1670 Initial Assessment of Adaptive Pancreas SBRT Treatment Efficiency using ViewRay MRIdian A3i

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions.

Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care.

Treatment of glioblastoma using MRIdian® A3i BrainTx™: Imaging and treatment workflow demonstration.

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

Assessment of intrafractional prostate motion and its dosimetric impact in MRI-guided online adaptive radiotherapy with gating

PurposeThis study aimed to evaluate the intrafractional prostate motion captured during gated magnetic resonance imaging (MRI)-guided online adaptive radiotherapy for prostate cancer and analyze its impact on the delivered dose as well as the effect of gating.MethodsSagittal 2D cine-MRI scans were acquired at 4 Hz during treatment at a ViewRay MRIdian (ViewRay Inc., Oakwood Village, OH, USA) MR linac. Prostate shifts in anterior–posterior (AP) and superior–inferior (SI) directions were extracted separately. Using the static dose cloud approximation, the planned fractional dose was shifted according to the 2D gated motion (residual motion in gating window) to estimate the delivered dose by superimposing and averaging the shifted dose volumes. The dose of a hypothetical non-gated delivery was reconstructed similarly using the non-gated motion. For the clinical target volume (CTV), rectum, and bladder, dose–volume histogram parameters of the planned and reconstructed doses were compared.ResultsIn total, 174 fractions (15.7 h of cine-MRI) from 10 patients were evaluated. The average (±1 σ) non-gated prostate motion was 0.6 ± 1.0 mm in the AP and 0.0 ± 0.6 mm in the SI direction with respect to the centroid position of the gating boundary. 95% of the shifts were within [−3.5, 2.7] mm in the AP and [−2.9, 3.2] mm in the SI direction. For the gated treatment and averaged over all fractions, CTV D98% decreased by less than 2% for all patients. The rectum and the bladder D2% increased by less than 3% and 0.5%, respectively. Doses reconstructed for gated and non-gated delivery were similar for most fractions.ConclusionA pipeline for extraction of prostate motion during gated MRI-guided radiotherapy based on 2D cine-MRI was implemented. The 2D motion data enabled an approximate estimation of the delivered dose. For the majority of fractions, the benefit of gating was negligible, and clinical dosimetric constraints were met, indicating safety of the currently adopted gated MRI-guided treatment workflow.

Synthetic CT generation for MRI-guided adaptive radiotherapy in prostate cancer.

Current MRI-guided adaptive radiotherapy (MRgART) workflows require fraction-specific electron and/or mass density maps, which are created by deformable image registration (DIR) between the simulation CT images and daily MR images. Manual density overrides may also be needed where DIR-produced results are inaccurate. This approach slows the adaptive radiotherapy workflow and introduces additional dosimetric uncertainties, especially in the presence of the magnetic field. This study investigated a method based on a conditional generative adversarial network (cGAN) with a multi-planar method to generate synthetic CT images from low-field MR images to improve efficiency in MRgART workflows for prostate cancer. Fifty-seven male patients, who received MRI-guided radiation therapy to the pelvis using the ViewRay MRIdian Linac, were selected. Forty-five cases were randomly assigned to the training cohort with the remaining twelve cases assigned to the validation/testing cohort. All patient datasets had a semi-paired DIR-deformed CT-sim image and 0.35T MR image acquired using a true fast imaging with steady-state precession (TrueFISP) sequence. Synthetic CT images were compared with deformed CT images to evaluate image quality and dosimetric accuracy. To evaluate the dosimetric accuracy of this method, clinical plans were recalculated on synthetic CT images in the MRIdian treatment planning system. Dose volume histograms for planning target volumes (PTVs) and organs-at-risk (OARs) and dose distributions using gamma analyses were evaluated. The mean-absolute-errors (MAEs) in CT numbers were 30.1 ± 4.2 HU, 19.6 ± 2.3 HU and 158.5 ± 26.0 HU for the whole pelvis, soft tissue, and bone, respectively. The peak signal-to-noise ratio was 35.2 ± 1.7 and the structural index similarity measure was 0.9758 ± 0.0035. The dosimetric difference was on average less than 1% for all PTV and OAR metrics. Plans showed good agreement with gamma pass rates of 99% and 99.9% for 1%/1 mm and 2%/2 mm, respectively. Our study demonstrates the potential of using synthetic CT images created with a multi-planar cGAN method from 0.35T MRI TrueFISP images for the MRgART treatment of prostate radiotherapy. Future work will validate the method in a large cohort of patients and investigate the limitations of the method in the adaptive workflow.

Time-resolved plastic scintillator dosimetry in MR linear accelerators without image distortion

One of the newest developments within radiotherapy is the integration of Magnetic Resonance (MR) scanners and Megavoltage X-rays from linear accelerators into the new MR-Linacs. Some MR-Linacs are able to perform gated treatments based on continuously acquired 2D MR images taken during dose delivery, which has the potential to reduce margins required for tumor coverage. We have developed a dosimetry system that can provide time-resolved, dose-per-pulse, dosimetry without distorting the MR images in order to characterize this technology. The system is based on a plastic BCF-60 scintillation detector (PSD) coupled to an optical PMMA fiber cable. The detector was placed in a plastic tube filled with water and inserted into the piston of a dynamic MRI compatible phantom to be treated on a ViewRay MRIdian 0.35 T MR-Linac. The piston performed a sinusoidal movement to simulate a breathing cycle of either 4 or 8 s. We demonstrate that the detector system is able to provide real-time dose-per-pulse measurements without causing distortions in the MR images. The time-resolved dosimetry system revealed systematic dose rate transients during gated treatments that lasted about 1 s in every gating sequence where the beam turned on and off. Detection of such effects require real time dosimetry which does not interfere with the MRI based gating.

Commissioning a secondary dose calculation software for a 0.35T MR-linac.

Secondary external dose calculations for a 0.35 T magnetic resonance image‐guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations.Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. The introduction of double‐stacked multi‐leaf collimator leaves was also included in the monitor unit calculations and a single transmission value was determined. A suite of simple and complex geometries with a variety field arrangements were calculated for each method to demonstrate the effect of the 0.35 T magnetic field on monitor unit calculations. Finally, 25 patient‐specific treatment plans were calculated using each method for comparison.All simple geometries calculated in RadCalc were within 2% of treatment planning system (TPS) values for both methods, except for a single noMag off‐axis comparison. All complex muilt‐leaf collimator (MLC) pattern calculations were within 5%. All complex phantom geometry calculations were within 5% except for a single field within a lung phantom at a distal point. For the patient calculations, the noMag method average percentage difference was 0.09 ± 2.5% and the wMag average percentage difference was 0.08 ± 2.5%. All results were within 5% for the wMag method.We performed monitor unit calculations for a 0.35 T MRgRT system using a commercially available secondary monitor unit dose calculation software and demonstrated minimal impact of the 0.35 T magnetic field on monitor unit dose calculations. This is the first investigation demonstrating successful calculations of dose using RadCalc in the low‐field 0.35 T ViewRay MRIdian system.

Technical note: Toward implementation of MR‐guided radiation therapy for laryngeal cancer with healthy volunteer imaging and a custom MR‐CT larynx phantom

Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments. A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation. A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2mm). The MR-Linac was able to visualize, track, and gate larynx motion. The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac.

Initial observation of contrast profiles for 3D and 2D MRI sequences in MR-guided radiation therapy for locally advanced pancreatic cancer.

541 Background: MR-guided stereotactic body radiation therapy (MR-SBRT) is a novel method of treating mobile tumors with soft-tissue gating and on-table adaptive planning. In our experience using the ViewRay MRIdian system (VR) for treating locally advanced pancreatic cancer (PA) with MR-SBRT, the true-fast imaging with steady-state free precession (TRUFI) sequences on the VR impart differing intensities for relevant structures seen on the pre-treatment high resolution 3D MRI (3D MRI) versus the real-time 2D cine MRI (2D cine) used for target tracking. Since these variations can confound target tracking selection, we propose that an understanding of the differing contrast profiles could improve selection of tracking structures and optimize treatment delivery. Methods: We retrospectively reviewed both 3D MRI and 2D cine images for patients (pts) with PA (n =20) treated on the VR. At simulation, an appropriate tracking target was identified and contoured on a single 3mm sagittal slice of the 3D MRI. This sagittal slice was directly compared to the registered 7mm 2D cine to identify structures with notable discrepancies in signal intensity. The 3D MRI was then explored in additional planes to confirm structure identities. For quantitative verification of the clinically observed differences, the pixel intensity distributions of 3D MRI and 2D cine DICOM image datasets were statistically compared. Results: In all pts reviewed, arteries (aorta, celiac, SMA) appeared with similar contrast profiles on both images. However, veins (portal vein, SMV) appeared hypointense on 3D MRI but hyperintense on 2D cine. Biliary structures appeared hyperintense on 3D MRI but only mildly hyperintense on 2D cine. The pixel intensity distributions extracted from 3D MRI and 2D cine images were confirmed to differ significantly (two sample Kolmogorov-Smirnov test; test statistic =0.40; p < 0.001). Conclusions: There are significant variations in image intensity between the initial treatment planning 3D MRI and the immediate pre-treatment 2D cine obtained with the VR. Understanding these discrepancies can guide radiation oncologists in choosing optimal tracking targets. Future work will focus on identifying the particular causes and frequencies of target tracking failures and exploring alternative tracking algorithms using artificial intelligence which could ultimately allow for VMAT on the ViewRay system.

Tumor volume regression of rectal cancer in daily MRI during preoperative chemoradiotherapy with capecitabine.

123 Background: Although cone beam computed tomography (CBCT) has been available for over a decade, the pattern of tumor volume change in rectal dancer during preoperative concurrent chemoradiotherapy (CCRT) has been under the veil due to poor soft tissue contrast of registration CBCT. This study was conducted to investigate daily rectal tumor volume change using registration magnetic resonance imaging (MRI). Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by single physician (YKK) in daily 0.35T MRI obtained with ViewRay MRIdian Linac (ViewRay Inc., Oakwood, USA). The mean +/- standard deviation (SD) of daily tumor volume (cc), difference of tumor volume between first fraction and daily fraction (daily tumor volume – baseline tumor volume at first fraction), and tumor volume reduction rate (%, (daily tumor volume – baseline tumor volume at first fraction)/baseline tumor volume at first fraction x 100) were calculated. Statistical significance of differences were tested using the Wilcoxon’s signed rank test and paired t-test. Results: Thirteen patients were included. Median age was 65 and majority of the patients were male (92.3%). Most tumors were T3 (76.9%) and N1-2 (92.3%). Tumors were located median 6 cm (range: 2.4 – 9) above anal verge. Median follow-up was 27.3 months (range: 11.7 – 30.6) and 2 patients had recurred at the time of analysis (1 local and 1 distant). Tumor volume steadily regressed with daily administration of CCRT (mean 2.06 +/-1.73 cc; Figure 1). Significant tumor volume reduction compared to baseline was observed from fourth fraction (mean -12.37 +/- 16.72 cc; P < 0.0005). The difference of tumor volume between baseline and the last fraction was mean -49.33 +/- 68.13 cc ( P < 0.0002). The tumor volume reduction rate was significantly increased since fourth fraction (mean - 17.2 +/- 11.78 %; P < 0.0002). The tumor volume reduction rate at the last fraction was - 70.62 +/- 14.01 % ( P < 0.0001). Conclusions: For the first time, this study demonstrated daily tumor volume regression in preoperative rectal CCRT with capecitabine using daily MRI. Steady pattern of tumor regression may be explained in part by daily administration of capecitabine. Based on the hypothesis-generating observation, this study may warrant initiation of further investigations such as analysis and comparison with daily tumor volume regression with CCRT using leucovorin and 5-FU.

Technical Note: An alternative approach to verify 6FFF beam dosimetry for Ethos and MR Linac without using a 3D water tank.

The current approach to Linac beam dosimetry verification is typically performed utilizing a three-dimensional (3D) water tank system. The 3D beam scanning process is cumbersome, labor intensive, error-prone, and costly. This is especially challenging for the new Ethos system and MR Linacs with a ring gantry. This work proposes an alternative approach to verify 6FFF beam dosimetry for Ethos, ViewRay MRIdian® Linac, and other Linacs with 6FFF beam quality using two-dimensional (2D) ion chamber arrays. Percentage depth dose (PDD) and profiles of an Ethos, an MRIdian® Linac, and several Linacs with 6FFF beams were measured at the nominal beam current. The beam energy was detuned by changing the bending magnet current on one TrueBeam. PDDs and profiles were measured for detuned beam energies. The peak shape of the 6FFF profile was defined by a "slope" parameter and unflatness. Correlations between peak slope and unflatness metrics vs PDDs were used to evaluate the sensitivity of beam energy to beam profile changes at different field sizes and depths. Strong correlations were found between peak slope and PDDs for all Linacs with 6FFF beam. The R-squared values in the linear regression fitting between PDD and peak slope and unflatness were 0.99 and 0.84, respectively. Both profile slope and unflatness were proportional to PDD at the 10cm depth and the peak slope was 4.3 times more sensitive than PDD. We have identified that measurements with a shallow depth are preferred to quantify the beam energy consistency. Our work shows the feasibility of verifying 6FFF beam quality of Ethos, MR Linac, and other Linacs by defining a profile slope measured from 2D ionization chambers array devices. This new approach provides a simplified method for performing a routine beam quality check without using a 3D water tank system while maximizing cost effectiveness and efficiency.