Technical note: A simple method for patient-specific quality assurance for lateral targets on a 1.5 T MR-Linac.

The Elekta Unity magnetic resonance (MR) linac is limited to longitudinal couch motion and a sagittal-only laser, which restricts the ability to perform patient-specific quality assurance (PSQA) intensity-modulated radiotherapy (IMRT) measurements for very lateral targets. This work introduces a simple method to perform PSQA using the Sun Nuclear ArcCheck-MR phantom at left and right lateral positions without additional equipment or in-house construction. The proposed setup places the center of the phantom 1.3 cm vertical and 12.9 cm lateral to isocenter in either the left or right direction. Computed tomography (CT) scans are used to simulate the setup and create a QA plan template in the Monaco treatment planning system (TPS). The workflow is demonstrated for four patients, with an average axial distance from the center of the bore to the planning target volume (PTV) of 12.4 cm. Gamma pass rates were above 94% for all plans using global 3%/2 mm gamma criterion with a 10% threshold. Setup uncertainties are slightly larger for the proposed lateral setup compared to the centered setup on the Elekta platform (∼1 mm compared to ∼0.5 mm), but acceptable pass rates are achievable without optimizing shifts in the gamma analysis software. In general, adding the left and right lateral positions increases the axial area in the bore encompassed by the cylindrical measurement array by 147%, substantially increasing the flexibility of measurements for offset targets. Based on this work, we propose using the lateral QA setup if the closest distance to the PTV edge from isocenter is larger than the array radius (10.5 cm) or the percent of the PTV encompassed by the diode array would be increased with the lateral setup compared to the centered setup.

A Technique to Enable Efficient Adaptive Radiation Therapy: Automated Contouring of Prostate and Adjacent Organs.

Purpose: The purpose of this work was to investigate the use of a segmentation approach that could potentially improve the speed and reproducibility of contouring during magnetic resonance-guided adaptive radiation therapy. Methods and Materials: The segmentation algorithm was based on a hybrid deep neural network and graph optimization approach that also allows rapid user intervention (Deep layered optimal graph image segmentation of multiple objects and surfaces [LOGISMOS] + just enough interaction [JEI]). A total of 115 magnetic resonance-data sets were used for training and quantitative assessment. Expert segmentations were used as the independent standard for the prostate, seminal vesicles, bladder, rectum, and femoral heads for all 115 data sets. In addition, 3 independent radiation oncologists contoured the prostate, seminal vesicles, and rectum for a subset of patients such that the interobserver variability could be quantified. Consensus contours were then generated from these independent contours using a simultaneous truth and performance level estimation approach, and the deviation of Deep LOGISMOS + JEI contours to the consensus contours was evaluated and compared with the interobserver variability. Results: The absolute accuracy of Deep LOGISMOS + JEI generated contours was evaluated using median absolute surface-to-surface distance which ranged from a minimum of 0.20 mm for the bladder to a maximum of 0.93 mm for the prostate compared with the independent standard across all data sets. The median relative surface-to-surface distance was less than 0.17 mm for all organs, indicating that the Deep LOGISMOS + JEI algorithm did not exhibit a systematic under- or oversegmentation. Interobserver variability testing yielded a mean absolute surface-to-surface distance of 0.93, 1.04, and 0.81 mm for the prostate, seminal vesicles, and rectum, respectively. In comparison, the deviation of Deep LOGISMOS + JEI from consensus simultaneous truth and performance level estimation contours was 0.57, 0.64, and 0.55 mm for the same organs. On average, the Deep LOGISMOS algorithm took less than 26 seconds for contour segmentation. Conclusions: Deep LOGISMOS + JEI segmentation efficiently generated clinically acceptable prostate and normal tissue contours, potentially limiting the need for time intensive manual contouring with each fraction.

MRI-Guided High-Dose-Rate Gynecologic Brachytherapy Using an MR-Linac as an MR Simulator: A Single Institutional Experience.

PURPOSE: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development. METHODS AND MATERIALS: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New workflows were developed which were tested with a full dry run with a healthy volunteer including patient transfer, anesthesia considerations, and data transfer. Validation of the workflow was completed on 1 patient who received imaging on both the Unity magnetic resonance imaging (MRI) and on a dedicated 3 Tesla MRI simulator. RESULTS: Imaging analysis results were favorable with MR-linac images with a maximum distortion of 0.96 mm and a 1.36-mm over a 350-mm diameter spherical volume on the T1- and T2-weighted images, respectively, and the maximum effect of the applicator was 0.36 ppm of the main magnetic field. Reconstruction uncertainties of the Venezia applicator's tandem and 2 lunar-ovoids on the MR-linac images were within the 2-mm tolerance of the International Commission on Radiation Units and Measurements Report 89. Treatment planning and delivery was performed on the MR-HDR quality assurance phantom without issue. Dry run and healthy volunteer imaging showed adequate performance of both vital monitoring and HDR equipment. For the patient for which both the Unity MRI and 3 Tesla images were acquired, 95.78% and 95.80% of the high risk clinical target volume received 100% of the dose, respectively. Both plans were considered clinically acceptable. CONCLUSIONS: Unity MR-linac images were successfully used in gynecologic HDR brachytherapy treatment planning, and a usable workflow was established.

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

PURPOSE: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. PATIENTS AND METHODS: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. RESULTS: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. CONCLUSIONS: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255.

Intra-fraction motion of pelvic oligometastases and feasibility of PTV margin reduction using MRI guided adaptive radiotherapy.

Purpose: This study assesses the impact of intra-fraction motion and PTV margin size on target coverage for patients undergoing radiation treatment of pelvic oligometastases. Dosimetric sparing of the bowel as a function of the PTV margin is also evaluated. Materials and methods: Seven patients with pelvic oligometastases previously treated on our MR-linac (35 Gy in 5 fractions) were included in this study. Retrospective adaptive plans were created for each fraction on the daily MRI datasets using PTV margins of 5 mm, 3 mm, and 2 mm. Dosimetric constraint violations and GTV coverage were measured as a function of PTV margin size. The impact of intra-fraction motion on GTV coverage was assessed by tracking the GTV position on the cine MR images acquired during treatment delivery and creating an intra-fraction dose distribution for each IMRT beam. The intra-fraction dose was accumulated for each fraction to determine the total dose delivered to the target for each PTV size. Results: All OAR constraints were achieved in 85.7%, 94.3%, and 100.0% of fractions when using 5 mm, 3 mm, and 2 mm PTV margins while scaling to 95% PTV coverage. Compared to plans with a 5 mm PTV margin, there was a 27.4 ± 12.3% (4.0 ± 2.2 Gy) and an 18.5 ± 7.3% (2.7 ± 1.4 Gy) reduction in the bowel D0.5cc dose for 2 mm and 3 mm PTV margins, respectively. The target dose (GTV V35 Gy) was on average 100.0 ± 0.1% (99.6 - 100%), 99.6 ± 1.0% (97.2 - 100%), and 99.0 ± 1.4% (95.0 - 100%), among all fractions for the 5 mm, 3 mm, and 2 mm PTV margins on the adaptive plans when accounting for intra-fraction motion, respectively. Conclusion: A 2 mm PTV margin achieved a minimum of 95% GTV coverage while reducing the dose to the bowel for all patients.

Initial clinical applications treating pediatric and adolescent patients using MR-guided radiotherapy.

Purpose: To demonstrate the clinical applications and feasibility of online adaptive magnetic resonance image guided radiotherapy (MRgRT) in the pediatric, adolescent and young adult (AYA) population. Methods: This is a retrospective case series of patients enrolled onto a prospective study. All pediatric (age < 18) and AYA patients (age< 30), treated on the Elekta Unity MR linear accelerator (MRL) from 2019 to 2021 were enrolled onto a prospective registry. Rationale for MRgRT included improved visualization of and alignment to the primary tumor, re-irradiation in a critical area, ability to use smaller margins, and need for daily adaptive replanning to minimize dose to adjacent critical structures. Step-and-shoot intensity-modulated radiation treatment (IMRT) plans were generated for all Unity patients with a dose grid of 3 mm and a statistical uncertainty of < 1% per plan. Results: A total of 15 pediatric and AYA patients have been treated with median age of 13 years (range: 6 mos - 27 yrs). Seven patients were <10 yo. The clinical applications of MRgRT included Wilms tumor with unresectable IVC thrombus (n=1), Ewing sarcoma (primary and metastatic, n=3), recurrent diffuse intrinsic pontine glioma (DIPG, n=2), nasopharyngeal carcinoma (n=1), clival chordoma (n=1), primitive neuroectodermal tumor of the pancreas (n=1), recurrent gluteo-sacral germ cell tumor (n=1), C-spine ependymoma (n=1), and posterior fossa ependymoma (n=1). Two children required general anesthesia. One AYA patient could not complete the MRgRT course due to tumor-related pain exacerbated by longer treatment times. Two AYA patients experienced anxiety related to treatment on the MRL, one of which required daily Ativan. No patient experienced treatment interruptions or unexpected toxicity. Conclusion: MRgRT was well-tolerated by pediatric and AYA patients. There was no increased use of anesthesia outside of our usual practice. Dosimetric advantages were seen for patients with tumors in critical locations such as adjacent to or involving optic structures, stomach, kidney, bowel, and heart.

Clinical Implementational and Site-Specific Workflows for a 1.5T MR-Linac.

MR-guided adaptive radiotherapy (MRgART) provides opportunities to benefit patients through enhanced use of advanced imaging during treatment for many patients with various cancer treatment sites. This novel technology presents many new challenges which vary based on anatomic treatment location, technique, and potential changes of both tumor and normal tissue during treatment. When introducing new treatment sites, considerations regarding appropriate patient selection, treatment planning, immobilization, and plan-adaption criteria must be thoroughly explored to ensure adequate treatments are performed. This paper presents an institution's experience in developing a MRgART program for a 1.5T MR-linac for the first 234 patients. The paper suggests practical treatment workflows and considerations for treating with MRgART at different anatomical sites, including imaging guidelines, patient immobilization, adaptive workflows, and utilization of bolus.

Reducing MRI-guided radiotherapy planning and delivery times via efficient leaf sequencing and segment shape optimization algorithms.

Objective.Extended treatment session times are an operational limitation in magnetic resonance imaging guided adaptive radiotherapy (MRIgRT). In this study a novel leaf sequencing algorithm called optimal fluence levels (OFL) and an optimization algorithm called pseudo gradient descent (PGD) are evaluated with respect to plan quality, beam complexity, and the ability to reduce treatment session times on the Elekta Unity MRIgRT system.Approach.Ten total patients were evaluated on this Institutional Review Board approved study: three with prostate cancer, three with oligometastases, two with pancreatic cancer, and two with liver cancer. Plans were generated using the clinical Monaco Hyperion optimizer and leaf sequencer and then re-optimized using OFL and PGD (OFL + PGD) while holding all IMRT constraints and planning parameters constant. All plans were normalized to ensure 95% of the PTV received the prescription dose. A paired t-test was used to evaluate statistical significance.Main Results.Plan quality in terms of dosimetric OAR sparing was found to be equivalent between the OFL + PGD and conventional Monaco Hyperion optimizer plans. The OFL + PGD plans had a reduction in optimization time of 51.4% ± 5.0% (p = 0.002) and reduction in treatment delivery time of 10.6% ± 7.5% (p = 0.005). OFL + PGD generated plans had on average 13.2% ± 12.6% fewer multi-leaf collimator (MLC) segments (p = 0.009) and 0.1 ± 0.1 lower plan averaged beam modulation (PM) (p = 0.004) relative to the Monaco Hyperion plans.Significance.The OFL + PGD algorithms more quickly generate Unity treatment plans that are faster to deliver than with the conventional approach and without compromising dosimetric plan quality. This is likely due to a delivery complexity reduction enabled by OFL + PGD relative to the Monaco Hyperion plans.

Analysis of patient-specific quality assurance for Elekta Unity adaptive plans using statistical process control methodology.

The Elekta Unity MR-linac utilizes daily magnetic resonance imaging (MRI) for online plan adaptation. In the Unity workflow, adapt to position (ATP) and adapt to shape (ATS) treatment planning options are available which represent a virtual shift or full re-plan with contour adjustments respectively. Both techniques generate a new intensity modulated radiation therapy (IMRT) treatment plan while the patient lies on the treatment table and thus adapted plans cannot be measured prior to treatment delivery. A statistical process control methodology was used to analyze 512 patient-specific IMRT QA measurements performed on the MR-compatible SunNuclear ArcCheck with a gamma criterion of 3%/2 mm using global normalization and a 10% low dose threshold. The lower control limit (LCL) was determined from 68 IMRT reference plan measurements, and a one-sided process capability ratio ( C p , l ) was used to assess the pass rates from 432 measured ATP and 80 measured ATS plans. Further analysis was performed to assess differences between SBRT or conventional fractionation pass rates and to determine whether there was any correlation between the pass rates and plan complexity. The LCL of the reference plans was determined to be a gamma pass rate of 0.958, and the C p , l of the measured ATP plans and measured ATS plans were determined to be 1.403 and 0.940 for ATP and ATS plans, respectively, while a C p , l of 0.902 and 1.383 was found for SBRT and conventional fractionations respectively. For plan complexity, no correlation was found between modulation degree and gamma pass rate, but a statistically significant correlation was observed between the beam-averaged aperture area and gamma pass rate. All adaptive plans passed the TG-218 guidelines, but the ATS and SBRT plans tended to have a smaller beam-averaged aperture area with slightly lower gamma pass rates.

Magnetic resonance imaging (MRI) of pharmacological ascorbate-induced iron redox state as a biomarker in subjects undergoing radio-chemotherapy.

Pharmacological ascorbate (P-AscH-) combined with standard of care (SOC) radiation and temozolomide is being evaluated in a phase 2 clinical trial (NCT02344355) in the treatment of glioblastoma (GBM). Previously published data demonstrated that paramagnetic iron (Fe3+) catalyzes ascorbate's oxidation to form diamagnetic iron (Fe2+). Because paramagnetic Fe3+ may influence relaxation times observed in MR imaging, quantitative MR imaging of P-AscH--induced changes in redox-active Fe was assessed as a biomarker for therapy response. Gel phantoms containing either Fe3+ or Fe2+ were imaged with T2* and quantitative susceptibility mapping (QSM). Fifteen subjects receiving P-AscH- plus SOC underwent T2* and QSM imaging four weeks into treatment. Subjects were scanned: pre-P-AscH- infusion, post-P-AscH- infusion, and post-radiation (3-4 h between scans). Changes in T2* and QSM relaxation times in tumor and normal tissue were calculated and compared to changes in Fe3+ and Fe2+ gel phantoms. A GBM mouse model was used to study the relationship between the imaging findings and the labile iron pool. Phantoms containing Fe3+ demonstrated detectable changes in T2* and QSM relaxation times relative to Fe2+ phantoms. Compared to pre-P-AscH-, GBM T2* and QSM imaging were significantly changed post-P-AscH- infusion consistent with conversion of Fe3+ to Fe2+. No significant changes in T2* or QSM were observed in normal brain tissue. There was moderate concordance between T2* and QSM changes in both progression free survival and overall survival. The GBM mouse model showed similar results with P-AscH- inducing greater changes in tumor labile iron pools compared to the normal tissue. CONCLUSIONS: T2* and QSM MR-imaging responses are consistent with P-AscH- reducing Fe3+ to Fe2+, selectively in GBM tumor volumes and represent a potential biomarker of response. This study is the first application using MR imaging in humans to measure P-AscH--induced changes in redox-active iron.

Assessment of Gadobutrol Safety in Combination with Ionizing Radiation Using a Preclinical MRI-Guided Radiotherapy Model.

MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered safe, previous literature suggests that GBCAs are capable of contrast-induced acute kidney injury (AKI). It is unclear if the risk for AKI is enhanced when GBCAs are administered concurrently with ionizing radiotherapy. During irradiation, gadolinium may be liberated from its chelator which may induce AKI. The goal of this work was to determine if radiation combined with GBCAs increased the incidence of AKI. Using a preclinical MRI-guided irradiation system, where MRI acquisitions and radiation delivery are performed in rapid succession, tumor-bearing mice with normal kidney function were injected with GBCA and treated with 2, 8 or 18 Gy irradiation. Renal function was assessed on days three and seven postirradiation to assess for AKI. No clinically relevant changes in blood urea nitrogen and creatinine were observed in any combination of GBCA and radiation dose. From these data, we conclude that GBCA in combination with radiation does not increase the risk for AKI in mice. Additional investigation of multiple doses of GBCA administered concurrently with irradiation is warranted to evaluate the risk of chronic kidney injury.

Stereotactic radiotherapy of appropriately selected meningiomas and metastatic brain tumor beds with gamma knife icon versus volumetric modulated arc therapy.

PURPOSE: To determine if the gamma knife icon (GKI) can provide superior stereotactic radiotherapy (SRT) dose distributions for appropriately selected meningioma and post-resection brain tumor bed treatments to volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: Appropriately selected targets were not proximal to great vessels, did not have sensitive soft tissue including organs-at-risk (OARs) within the planning target volume (PTV), and did not have concave tumors containing excessive normal brain tissue. Four of fourteen candidate meningioma patients and six of six candidate patients with brain tumor cavities were considered for this treatment planning comparison study. PTVs were generated for GKI and VMAT by adding 1 mm and 3 mm margins, respectively, to the GTVs. Identical PTV V100% -values were obtained for the GKI and VMAT plans for each patient. Meningioma and tumor bed prescription doses were 52.7-54.0 in 1.7-1.8 Gy fractions and 25 Gy in 5 Gy fractions, respectively. GKI dose rate was 3.735 Gy/min for 16 mm collimators. RESULTS: PTV radical dose homogeneity index was 3.03 ± 0.35 for GKI and 1.27 ± 0.19 for VMAT. Normal brain D1% , D5% , and D10% were lower for GKI than VMAT by 45.8 ± 10.9%, 38.9 ± 11.5%, and 35.4 ± 16.5% respectively. All OARs considered received lower maximum doses for GKI than VMAT. GKI and VMAT treatment times for meningioma plans were 12.1 ± 4.13 min and 6.2 ± 0.32 min, respectively, and, for tumor cavities, were 18.1 ± 5.1 min and 11.0 ± 0.56 min, respectively. CONCLUSIONS: Appropriately selected meningioma and brain tumor bed patients may benefit from GKI-based SRT due to the decreased normal brain and OAR doses relative to VMAT enabled by smaller margins. Care must be taken in meningioma patient selection for SRT with the GKI, even if they are clinically appropriate for VMAT.

Commissioning of a 1.5T Elekta Unity MR-linac: A single institution experience.

MR image-guided radiotherapy has the potential to improve patient care, but integration of an MRI scanner with a linear accelerator adds complexity to the commissioning process. This work describes a single institution experience of commissioning an Elekta Unity MR-linac, including mechanical testing, MRI scanner commissioning, and dosimetric validation. Mechanical testing included multileaf collimator (MLC) positional accuracy, measurement of radiation isocenter diameter, and MR-to-MV coincidence. Key MRI tests included magnetic field homogeneity, geometric accuracy, image quality, and the accuracy of navigator-triggered imaging for motion management. Dosimetric validation consisted of comparison between measured and calculated PDDs and profiles, IMRT measurements, and end-to-end testing. Multileaf collimator positional accuracy was within 1.0 mm, the measured radiation isocenter walkout was 0.20 mm, and the coincidence between MR and MV isocenter was 1.06 mm, which is accounted for in the treatment planning system (TPS). For a 350-mm-diameter spherical volume, the peak-to-peak deviation of the magnetic field homogeneity was 4.44 ppm and the geometric distortion was 0.8 mm. All image quality metrics were within ACR recommendations. Navigator-triggered images showed a maximum deviation of 0.42, 0.75, and 3.0 mm in the target centroid location compared to the stationary target for a 20 mm motion at 10, 15, and 20 breaths per minute, respectively. TPS-calculated PDDs and profiles showed excellent agreement with measurement. The gamma passing rate for IMRT plans was 98.4 ± 1.1% (3%/ 2 mm) and end-to-end testing of adapted plans showed agreement within 0.4% between ion-chamber measurement and TPS calculation. All credentialing criteria were satisfied in an independent end-to-end test using an IROC MRgRT phantom.

Feasibility of streamline upwind Petrov-Galerkin angular stabilization of the linear Boltzmann transport equation with magnetic fields.

To accurately model dose in a magnetic field, the Lorentz force must be included in the traditional linear Boltzmann transport equation (LBTE). Both angular and spatial stabilization are required to deterministically solve this equation. In this work, a streamline upwind Petrov-Galerkin (SUPG) method is applied to achieve angular stabilization of the LBTE with magnetic fields. The spectral radius of the angular SUPG method is evaluated using a Fourier analysis method to characterize the convergence properties. Simulations are then performed on homogeneous phantoms and two heterogeneous slab geometry phantoms containing water, bone, lung/air and water for 0.5 T parallel and 1.5 T perpendicular magnetic field configurations. Fourier analysis determined that the spectral radius of the SUPG scheme is unaffected by magnetic field strength and the SUPG free parameter, indicating that the Gauss-Seidel source iteration method is unconditionally stable and the convergence rate is not degraded with increasing magnetic field strength. 100% of simulation points passed a 3D gamma analysis at a 2%/2 mm (3%/3 mm) gamma criterion for both magnetic field configurations in the homogeneous phantom study, with the exception of the 1.5 T perpendicular magnetic field in the pure lung phantom where a 77.4% (87.0%) pass rate was achieved. Simulations in the lung slab geometry phantom resulted in 100% of points passing a 2%/2 mm gamma analysis in a 0.5 T parallel magnetic field, and 97.7% (98.8%) of points passing a 2%/2 mm (3%/3 mm) gamma criterion in a 1.5 T perpendicular magnetic field. For the air slab geometry phantom, 72.1% (79.2%) of points passed a 2%/2 mm gamma criterion in a 0.5 T parallel magnetic field and 90.3% (92.8%) passed the same gamma criterion in a 1.5 T perpendicular magnetic field. While the novel SUPG angular stabilization method shows feasibility in some cases, it was found that the accuracy of this method was degraded for very low density media such as air.

Commissioning and performance evaluation of RadCalc for the Elekta unity MRI-linac.

Recent availability of MRI-guided linear accelerators has introduced a number of clinical challenges, particularly in the context of online plan adaptation. Paramount among these is verification of plan quality prior to patient treatment. Currently, there are no commercial products available for monitor unit verification that fully support the newly FDA cleared Elekta Unity 1.5 T MRI-linac. In this work, we investigate the accuracy and precision of RadCalc for this purpose, which is a software package that uses a Clarkson integration algorithm for point dose calculation. To this end, 18 IMRT patient plans (186 individual beams) were created and used for RadCalc point dose calculations. In comparison with the primary treatment planning system (Monaco), mean point dose deviations of 0.0 ± 1.0% (n = 18) and 1.7 ± 12.4% (n = 186) were obtained on a per-plan and per-beam basis, respectively. The dose plane comparison functionality within RadCalc was found to be highly inaccurate, however, modest improvements could be made by artificially shifting jaws and multi leaf collimator positions to account for the dosimetric shift due to the magnetic field (67.3% vs 96.5% mean 5%/5 mm gamma pass rate).

An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.

For decades the field of radiation oncology has sought to improve the therapeutic ratio through innovations in physics, chemistry, and biology. To date, technological advancements in image guided beam delivery techniques have provided clinicians with their best options for improving this critical tool in cancer care. Medical physics has focused on the preferential targeting of tumors while minimizing the collateral dose to the surrounding normal tissues, yielding only incremental progress. However, recent developments involving ultra-high dose rate irradiation termed FLASH radiotherapy (FLASH-RT), that were initiated nearly 50 years ago, have stimulated a renaissance in the field of radiotherapy, long awaiting a breakthrough modality able to enhance therapeutic responses and limit normal tissue injury. Compared to conventional dose rates used clinically (0.1-0.2 Gy/s), FLASH can implement dose rates of electrons or X-rays in excess of 100 Gy/s. The implications of this ultra-fast delivery of dose are significant and need to be re-evaluated to appreciate the fundamental aspects underlying this seemingly unique radiobiology. The capability of FLASH to significantly spare normal tissue complications in multiple animal models, when compared to conventional rates of dose-delivery, while maintaining persistent growth inhibition of select tumor models has generated considerable excitement, as well as skepticism. Based on fundamental principles of radiation physics, radio-chemistry, and tumor vs. normal cell redox metabolism, this article presents a series of testable, biologically relevant hypotheses, which may help rationalize the differential effects of FLASH irradiation observed between normal tissue and tumors.

Corrigendum to "Stability analysis of a deterministic dose calculation for MRI-guided radiotherapy".

Modern effort in radiotherapy to address the challenges of tumor localization and motion has led to the development of MRI guided radiotherapy technologies. Accurate dose calculations must properly account for the effects of the MRI magnetic fields. Previous work has investigated the accuracy of a deterministic linear Boltzmann transport equation (LBTE) solver that includes magnetic field, but not the stability of the iterative solution method. In this work, we perform a stability analysis of this deterministic algorithm including an investigation of the convergence rate dependencies on the magnetic field, material density, energy, and anisotropy expansion. The iterative convergence rate of the continuous and discretized LBTE including magnetic fields is determined by analyzing the spectral radius using Fourier analysis for the stationary source iteration (SI) scheme. The spectral radius is calculated when the magnetic field is included (1) as a part of the iteration source, and (2) inside the streaming-collision operator. The non-stationary Krylov subspace solver GMRES is also investigated as a potential method to accelerate the iterative convergence, and an angular parallel computing methodology is investigated as a method to enhance the efficiency of the calculation. SI is found to be unstable when the magnetic field is part of the iteration source, but unconditionally stable when the magnetic field is included in the streaming-collision operator. The discretized LBTE with magnetic fields using a space-angle upwind stabilized discontinuous finite element method (DFEM) was also found to be unconditionally stable, but the spectral radius rapidly reaches unity for very low density media and increasing magnetic field strengths indicating arbitrarily slow convergence rates. However, GMRES is shown to significantly accelerate the DFEM convergence rate showing only a weak dependence on the magnetic field. In addition, the use of an angular parallel computing strategy is shown to potentially increase the efficiency of the dose calculation.

The design of a simulated in-line side-coupled 6 MV linear accelerator waveguide.

PURPOSE: The design of a 3D in-line side-coupled 6 MV linac waveguide for medical use is given, and the effect of the side-coupling and port irises on the radio frequency (RF), beam dynamics, and dosimetric solutions is examined. This work was motivated by our research on a linac-MR hybrid system, where accurate electron trajectory information for a clinical medical waveguide in the presence of an external magnetic field was needed. METHODS: For this work, the design of the linac waveguide was generated using the finite element method. The design outlined here incorporates the necessary geometric changes needed to incorporate a full-end accelerating cavity with a single-coupling iris, a waveguide-cavity coupling port iris that allows power transfer into the waveguide from the magnetron, as well as a method to control the RF field magnitude within the first half accelerating cavity into which the electrons from the gun are injected. RESULTS: With the full waveguide designed to resonate at 2998.5 +/- 0.1 MHz, a full 3D RF field solution was obtained. The accuracy of the 3D RF field solution was estimated through a comparison of important linac parameters (Q factor, shunt impedance, transit time factor, and resonant frequency) calculated for one accelerating cavity with the benchmarked program SUPERFISH. It was found that the maximum difference between the 3D solution and SUPERFISH was less than 0.03%. The eigenvalue solver, which determines the resonant frequencies of the 3D side-coupled waveguide simulation, was shown to be highly accurate through a comparison with lumped circuit theory. Two different waveguide geometries were examined, one incorporating a 0.5 mm first side cavity shift and another with a 1.5 mm first side cavity shift. The asymmetrically placed side-coupling irises and the port iris for both models were shown to introduce asymmetries in the RF field large enough to cause a peak shift and skewing (center of gravity minus peak shift) of an initially cylindrically uniform electron beam accelerating within the waveguide. The shifting and skewing of the electron beam were found to be greatest due to the effects of the side-coupling irises on the RF field. A further Monte Carlo study showed that this effect translated into a 1% asymmetry in a 40 x 40 cm2 field dose profile. CONCLUSIONS: A full 3D design for an in-line side-coupled 6 MV linear accelerator that emulates a common commercial waveguide has been given. The effect of the side coupling on the dose distribution has been shown to create a slight asymmetry, but overall does not affect the clinical applicability of the linac. The 3D in-line side-coupled linac model further provides a tool for the investigation of linac performance within an external magnetic field, which exists in an integrated linac-MR system.