Patterns of Locoregional Pancreatic Cancer Recurrence After Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes.

PURPOSE: To generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy or TNT) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting. METHODS: Locoregional recurrences following TNT followed by surgery treated between 2009-2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume (CTV) contour for patients treated with TNT. Recurrence patterns were also compared to existing adjuvant guidelines to assess coverage. RESULTS: A database of 484 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified eighty patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aortico-diaphragmatic junction, retro-pancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences. CONCLUSIONS: This is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented herein can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

Evaluation and mitigation of deformable image registration uncertainties for MRI-guided adaptive radiotherapy.

PURPOSE: We evaluate the performance of a deformable image registration (DIR) software package in registering abdominal magnetic resonance images (MRIs) and then develop a mechanical modeling method to mitigate detected DIR uncertainties. MATERIALS AND METHODS: Three evaluation metrics, namely mean displacement to agreement (MDA), DICE similarity coefficient (DSC), and standard deviation of Jacobian determinants (STD-JD), are used to assess the multi-modality (MM), contour-consistency (CC), and image-intensity (II)-based DIR algorithms in the MIM software package, as well as an in-house developed, contour matching-based finite element method (CM-FEM). Furthermore, we develop a hybrid FEM registration technique to modify the displacement vector field of each MIM registration. The MIM and FEM registrations were evaluated on MRIs obtained from 10 abdominal cancer patients. One-tailed Wilcoxon-Mann-Whitney (WMW) tests were conducted to compare the MIM registrations with their FEM modifications. RESULTS: For the registrations performed with the MIM-CC, MIM-MM, MIM-II, and CM-FEM algorithms, their average MDAs are 0.62 ± 0.27, 2.39 ± 1.30, 3.07 ± 2.42, 1.04 ± 0.72 mm, and average DSCs are 0.94 ± 0.03, 0.80 ± 0.12, 0.77 ± 0.15, 0.90 ± 0.11, respectively. The p-values of the WMW tests between the MIM registrations and their FEM modifications are less than 0.0084 for STD-JDs and greater than 0.87 for MDA and DSC. CONCLUSIONS: Among the three MIM DIR algorithms, MIM-CC shows the smallest errors in terms of MDA and DSC but exhibits significant Jacobian uncertainties in the interior regions of abdominal organs. The hybrid FEM technique effectively mitigates the Jacobian uncertainties in these regions.

Development of a comprehensive cardiac atlas on a 1.5 Tesla Magnetic Resonance Linear Accelerator.

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15-16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system.

Automated deep learning auto-segmentation of air volumes for MRI-guided online adaptive radiation therapy of abdominal tumors.

Objective. In the current MR-Linac online adaptive workflow, air regions on the MR images need to be manually delineated for abdominal targets, and then overridden by air density for dose calculation. Auto-delineation of these regions is desirable for speed purposes, but poses a challenge, since unlike computed tomography, they do not occupy all dark regions on the image. The purpose of this study is to develop an automated method to segment the air regions on MRI-guided adaptive radiation therapy (MRgART) of abdominal tumors.Approach. A modified ResUNet3D deep learning (DL)-based auto air delineation model was trained using 102 patients' MR images. The MR images were acquired by a dedicated in-house sequence named 'Air-Scan', which is designed to generate air regions that are especially dark and accentuated. The air volumes generated by the newly developed DL model were compared with the manual air contours using geometric similarity (Dice Similarity Coefficient (DSC)), and dosimetric equivalence using Gamma index and dose-volume parameters.Main results. The average DSC agreement between the DL generated and manual air contours is 99% ± 1%. The gamma index between the dose calculations with overriding the DL versus manual air volumes with density of 0.01 is 97% ± 2% for a local gamma calculation with a tolerance of 2% and 2 mm. The dosimetric parameters from planning target volume-PTV and organs at risk-OARs were all within 1% between when DL versus manual contours were overridden by air density. The model runs in less than five seconds on a PC with 28 Core processor and NVIDIA Quadro®P2000 GPU.Significance: a DL based automated segmentation method was developed to generate air volumes on specialized abdominal MR images and generate results that are practically equivalent to the manual contouring of air volumes.

Auto-detection of necessity for MRI-guided online adaptive replanning using a machine learning classifier.

PURPOSE: MRI-guided adaptive radiation therapy (MRgART), particularly daily online adaptive replanning (OLAR) can substantially improve radiation therapy delivery, however, it can be labor-intensive and time-consuming. Currently, the decision to perform OLAR for a treatment fraction is determined subjectively. In this work, we develop a machine learning algorithm based on structural similarity index measure (SSIM) and change in entropy to quickly and objectively determine whether OLAR is necessary for a daily MRI set. METHODS: A total of 109 daily MRI sets acquired on a 1.5T MR-Linac during MRgART for 22 pancreatic cancer patients each treated with five fractions were retrospectively analyzed. For each daily MRI set, OLAR and reposition (No-OLAR) plans were created and the superior plan with the daily fraction determined per clinical dose-volume criteria. SSIM and entropy maps were extracted from each daily MRI set, with respect to its reference (e.g., dry-run) MRI in the region enclosed by 50-100% isodose surfaces. A total of six common features were extracted from SSIM maps. Pearson's rank correlation coefficient was utilized to rule out redundant SSIM features. A t-test was used to determine significant SSIM features which were combined with the change in entropy to develop anensemble machine classifier with fivefold cross validation. The performance of the classifier was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A machine learning classifier model using two SSIM features (mean and full width at half maximum) and change in entropy was determined to be able to significantly discriminate between No-OLAR and OLAR groups. The obtained machine learning ensemble classifier can predict OLAR necessity with a cross validated AUC of 0.93. Misclassification was found primarily for No-OLAR cases with dosimetric plan quality closely comparable to the corresponding OLAR plans, thus, are not a major practical concern. CONCLUSION: A machine learning classifier based on simple first-order image features, that is, SSIM features and change in entropy, was developed to determine when OLAR is necessary for a daily MRI set with practical acceptable prediction accuracy. This classifier may be implemented in the MRgART process to automatically and objectively determine if OLAR is required following daily MRI.

Findings of the AAPM Ad Hoc committee on magnetic resonance imaging in radiation therapy: Unmet needs, opportunities, and recommendations.

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.

MR-Guided Radiotherapy for Brain and Spine Tumors.

MRI is the standard modality to assess anatomy and response to treatment in brain and spine tumors given its superb anatomic soft tissue contrast (e.g., T1 and T2) and numerous additional intrinsic contrast mechanisms that can be used to investigate physiology (e.g., diffusion, perfusion, spectroscopy). As such, hybrid MRI and radiotherapy (RT) devices hold unique promise for Magnetic Resonance guided Radiation Therapy (MRgRT). In the brain, MRgRT provides daily visualizations of evolving tumors that are not seen with cone beam CT guidance and cannot be fully characterized with occasional standalone MRI scans. Significant evolving anatomic changes during radiotherapy can be observed in patients with glioblastoma during the 6-week fractionated MRIgRT course. In this review, a case of rapidly changing symptomatic tumor is demonstrated for possible therapy adaptation. For stereotactic body RT of the spine, MRgRT acquires clear isotropic images of tumor in relation to spinal cord, cerebral spinal fluid, and nearby moving organs at risk such as bowel. This visualization allows for setup reassurance and the possibility of adaptive radiotherapy based on anatomy in difficult cases. A review of the literature for MR relaxometry, diffusion, perfusion, and spectroscopy during RT is also presented. These techniques are known to correlate with physiologic changes in the tumor such as cellularity, necrosis, and metabolism, and serve as early biomarkers of chemotherapy and RT response correlating with patient survival. While physiologic tumor investigations during RT have been limited by the feasibility and cost of obtaining frequent standalone MRIs, MRIgRT systems have enabled daily and widespread physiologic measurements. We demonstrate an example case of a poorly responding tumor on the 0.35 T MRIgRT system with relaxometry and diffusion measured several times per week. Future studies must elucidate which changes in MR-based physiologic metrics and at which timepoints best predict patient outcomes. This will lead to early treatment intensification for tumors identified to have the worst physiologic responses during RT in efforts to improve glioblastoma survival.

On the use of low-dimensional temporal subspace constraints to reduce reconstruction time and improve image quality of accelerated 4D-MRI.

BACKGROUND AND PURPOSE: The purpose of this work is to investigate the use of low-dimensional temporal subspace constraints for 4D-MRI reconstruction from accelerated data in the context of MR-guided online adaptive radiation therapy (MRgOART). MATERIALS AND METHODS: Subspace basis functions are derived directly from the accelerated golden angle radial stack-of-stars 4D-MRI data. The reconstruction times, image quality, and motion estimates are investigated as a function of the number of subspace coefficients and compared with a conventional frame-by-frame reconstruction. These experiments were performed in five patients with four 4D-MRI scans per patient on a 1.5T MR-Linac. RESULTS: If two or three subspace coefficients are used, the iterative reconstruction time is reduced by 32% and 18%, respectively, compared to conventional parallel imaging with compressed sensing reconstructions. No significant difference was found between motion estimates made with the subspace-constrained reconstructions (p > 0.08). Qualitative improvements in image quality included reduction in apparent noise and reductions in streaking artifacts from the radial k-space coverage. CONCLUSION: Incorporating subspace constraints for accelerated 4D-MRI reconstruction reduces noise and residual undersampling artifacts in the images while reducing computation time, making it a strong candidate for use in clinical MRgOART workflows.

Task group 284 report: magnetic resonance imaging simulation in radiotherapy: considerations for clinical implementation, optimization, and quality assurance.

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.

ADC measurements on the Unity MR-linac - A recommendation on behalf of the Elekta Unity MR-linac consortium.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasible on hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the Elekta Unity system has an adjusted design compared to diagnostic scanners. We investigated its impact on measuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice of b-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this study is to give recommendations for accurate ADC measurements on Unity systems. MATERIALS AND METHODS: Signal-to-noise ratio (SNR) measurements with increasing b-values were done to determine the highest bvalue that can be measured reliably. The spatial variation of the ADC was assessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotation and irradiation was investigated by acquiring DWI images before and during treatment of 11 prostate cancer patients. RESULTS: On the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, as a trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm from the iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influenced by the rotating linac or irradiation during treatment. CONCLUSION: We provide Unity system specific recommendations for measuring the ADC. This will increase the consistency of ADC values acquired in different centers on the Unity system, enabling large cohort studies for biomarker discovery and treatment response monitoring.

Initial clinical experience of Stereotactic Body Radiation Therapy (SBRT) for liver metastases, primary liver malignancy, and pancreatic cancer with 4D-MRI based online adaptation and real-time MRI monitoring using a 1.5 Tesla MR-Linac.

PURPOSE/OBJECTIVES: Recently a 1.5 Tesla MR Linac has been FDA approved and is commercially available. Clinical series describing treatment methods and outcomes for upper abdominal tumors using a 1.5 Tesla MR Linac are lacking. We present the first clinical series of upper abdominal tumors treated using a 1.5 Tesla MR Linac along with the acquisition of intra-treatment quantitative imaging. MATERIALS/METHODS: 10 patients with abdominal tumors were treated at our institution. Each patient enrolled in an IRB approved advanced imaging protocol. Both daily real-time adaptive and non-adaptive methods were used, and selection criteria are described. Adaptive plans were based on pre-beam motion-averaged or mid-position images derived from respiratory-correlated 4D-MRI. Quantitative intravoxel incoherent motion diffusion-weighted imaging and T2 mapping were acquired during plan adaptation. Real-time motion monitoring using cine MRI was performed during beam-on. RESULTS: Median patient age was 68.2, five patients were female. Tumor types included liver metastatic lesions from melanoma and sarcoma, primary liver hepatocellular carcinoma (HCC), and regional abdominal tumors included pancreatic metastatic lesions from renal cell carcinoma (RCC) along with two cases of recurrent pancreatic cancer. Doses included 30 Gy in 6 fractions, 33 Gy in 5 fractions, 50 Gy in 5 fractions, 45 Gy in 3 fractions, and 60 Gy in 3 fractions, depending on the location and clinical circumstances. Treatments were feasible and were successfully completed in all patients without significant acute toxicity, technical complications, or need for back up CT based treatment plans. CONCLUSIONS: We present a first clinical series of patients treated for pancreatic tumors, primary liver tumors, and secondary liver tumors with a 1.5 Tesla MR Linear accelerator using adapt-to-position and adapt-to-shape strategies. Treatments were well tolerated by all patients. Acquisition of fully quantitative MR imaging was feasible during the course of the treatment delivery workflow without extending overall treatment times.

4D-MRI driven MR-guided online adaptive radiotherapy for abdominal stereotactic body radiation therapy on a high field MR-Linac: Implementation and initial clinical experience.

BACKGROUND AND PURPOSE: In this report, we describe our implementation and initial clinical experience using 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) for abdominal stereotactic body radiotherapy (SBRT) on the Elekta Unity MR-Linac. MATERIALS AND METHODS: Eleven patients with abdominal malignancies were treated with free-breathing SBRT in three to five fractions on a 1.5 T MR-Linac. Online adaptive plans were generated using Adapt-To-Position (ATP) or Adapt-To-Shape (ATS) workflows based on motion averaged or mid-position images derived from a pre-beam 4D-MRI. A high performance server positioned on the local MR-Linac machine network was utilized for 4D-MR image reconstruction. A parallel contour editing approach was employed in the ATS workflow. Intravoxel incoherent motion (IVIM) and T2 mapping sequences were acquired during adaptive planning in both ATP and ATS workflows for treatment response monitoring. Adaptive plans were delivered under real-time cine image motion monitoring. RESULTS: The shortest 4D-MRI time-to-image was the motion averaged image, followed by mid position and respiratory binned images. In this cohert of patients, 50% of treatments utilized the ATS workflow; the remaining treatments utilized the ATP workflow. Mid-position images were utilized as daily planning images for two of the eleven patients. The mean daily adaptive plan secondary dose calculation and ArcCheck 3D Gamma passing rates were 97.5% (92.1-100.0%) and 99.3% (96.2-100.0%), respectively. The median overall treatment times for abdominal SBRT was 46 and 62 min for ATP and ATS workflows, respectively. CONCLUSION: We have successfully implemented and utilized a 4D-MRI driven MRgOART process with ATP and ATS workflows for free-breathing abdominal SBRT on a 1.5 T Elekta Unity MR-Linac.

A daily end-to-end quality assurance workflow for MR-guided online adaptive radiation therapy on MR-Linac.

PURPOSE: Magnetic Resonance (MR)-guided online adaptive radiation therapy (MRgOART), enabled with MR-Linac, has potential to revolutionize radiation therapy. MRgOART is a complex process. This work is to introduce a comprehensive end-to-end quality assurance (QA) workflow in routine clinic for MRgOART with a high-magnetic-field MR-Linac. MATERIALS AND METHOD: The major components in MRgOART with a high-magnetic field MR-Linac (Unity, Elekta) include: (1) a patient record and verification (R&V) system (e.g., Mosaiq, Elekta), (2) a treatment session manager, (3) an offline treatment planning system (TPS), (4) an online adaptive TPS, (5) a 1.5T MRI scanner, (6) an 7MV Linac, (7) an MV imaging controller (MVIC), and (8) ArtQA: software for plan data consistency checking and secondary dose calculation. Our end-to-end QA workflow was designed to test the performance and connectivity of all these components by transferring, adapting and delivering a specifically designed five-beam plan on a phantom. Beams 1-4 were designed to check Multi-Leaves Collimator (MLC) position shift based on rigid image registration in TPS, while beam 5 was used to check daily radiation output based on image pixel factor of MV image of the field. The workflow is initiated in the R&V system and followed by acquiring and registering daily MRI of the phantom, checking isocenter shift, performing online adaptive replanning, checking plan integrity and secondary 3D dose calculation, delivering the plan while acquiring MV imaging using MVIC, acquiring real-time images of the phantom, and checking the delivering parameters with ArtQA. RESULTS: It takes 10 min to finish the entire end-to-end QA workflow. The workflow has detected communication problems, permitted resolution prior to setting up patients for MRgOART. Up to 0.9 mm discrepancies in isocenter shift based on the image registration were detected. ArtQA performed the secondary 3D dose calculation, verified the plan integrity as well as the MR-MV isocenter alignment values in TPS. The MLC shapes of beam 1-4 in all adaptive plans were conformal to the target and agreed with MV images. The variation of daily output was within ±2.0%. CONCLUSIONS: The comprehensive end-to-end QA workflow can efficiently check the performance and communication between different components in MRgOART and has been successfully implemented for daily clinical practice.

Generalized simultaneous multi-orientation 2D imaging.

PURPOSE: Flexibility in slice prescription is critical for precise motion monitoring during MR-guided therapies. Adding more slices to improve spatial coverage during rapid 2D cine imaging often hampers temporal resolution. This work describes a framework to simultaneously acquire multiple arbitrarily oriented slices which share a common frequency encoding axis. This framework allows for higher frame rates for a given number of slices compared to conventional interleaved-slice multi-orientation cine imaging. THEORY AND METHODS: A framework to calculate zeroth gradient moments to be played out between sequentially excited slices with multiple orientations is described here. Experiments were performed in phantom, and in vivo in the head/neck and abdomen of patients. RESULTS: Images arbitrarily rotated relative to one another were successfully obtained in phantom and in vivo. Simultaneous multi-orientation (SMO) images were also acquired with additional in-plane acceleration to demonstrate the capability of this method to rapidly image objects moving with physiological motion. CONCLUSIONS: The technical feasibility of the generalized SMO imaging framework was tested in this study. It shows promise for continued development for motion monitoring during MR-guided therapies.

The transformation of radiation oncology using real-time magnetic resonance guidance: A review.

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation.

Measurement validation of treatment planning for a MR-Linac.

PURPOSE: The magnetic field can cause a nonnegligible dosimetric effect in an MR-Linac system. This effect should be accurately accounted for by the beam models in treatment planning systems (TPS). The purpose of the study was to verify the beam model and the entire treatment planning and delivery process for a 1.5 T MR-Linac based on comprehensive dosimetric measurements and end-to-end tests. MATERIAL AND METHODS: Dosimetry measurements and end-to-end tests were performed on a preclinical MR-Linac (Elekta AB) using a multitude of detectors and were compared to the corresponding beam model calculations from the TPS for the MR-Linac. Measurement devices included ion chambers (IC), diamond detector, radiochromic film, and MR-compatible ion chamber array and diode array. The dose in inhomogeneous phantom was also verified. The end-to-end tests include the generation, delivery, and comparison of 3D and IMRT plan with measurement. RESULTS: For the depth dose measurements with Farmer IC, micro IC and diamond detector, the absolute difference between most measurement points and beam model calculation beyond the buildup region were <1%, at most 2% for a few measurement points. For the beam profile measurements, the absolute differences were no more than 1% outside the penumbra region and no more than 2.5% inside the penumbra region. Results of end-to-end tests demonstrated that three 3D static plans with single 5 × 10 cm2 fields (at gantry angle 0°, 90° and 270°) and two IMRT plans successfully passed gamma analysis with clinical criteria. The dose difference in the inhomogeneous phantom between the calculation and measurement was within 1.0%. CONCLUSIONS: Both relative and absolute dosimetry measurements agreed well with the TPS calculation, indicating that the beam model for MR-Linac properly accounts for the magnetic field effect. The end-to-end tests verified the entire treatment planning process.

Feasibility and accuracy of quantitative imaging on a 1.5 T MR-linear accelerator.

PURPOSE: Systems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker discovery using quantitative MRI (qMRI). Here, the performance of a 1.5 T MR-linac regarding qMRI was assessed on phantoms. Additionally, we show the feasibility of qMRI in a prostate cancer patient on this system for the first time. MATERIALS AND METHODS: Four 1.5 T MR-linac systems from four institutes were included in this study. T1 and T2 relaxation times, and apparent diffusion coefficient (ADC) maps, as well as dynamic contrast enhanced (DCE) images were acquired. Bland-Altman statistics were used, and accuracy, repeatability, and reproducibility were determined. RESULTS: Median accuracy for T1 ranged over the four systems from 2.7 to 14.3%, for T2 from 10.4 to 14.1%, and for ADC from 1.9 to 2.7%. For DCE images, the accuracy ranged from 12.8 to 35.8% for a gadolinium concentration of 0.5 mM and deteriorated for higher concentrations. Median short-term repeatability for T1 ranged from 0.6 to 5.1%, for T2 from 0.4 to 1.2%, and for ADC from 1.3 to 2.2%. DCE acquisitions showed a coefficient of variation of 0.1-0.6% in the signal intensity. Long-term repeatability was 1.8% for T1, 1.4% for T2, 1.7% for ADC, and 17.9% for DCE. Reproducibility was 11.2% for T1, 2.9% for T2, 2.2% for ADC, and 18.4% for DCE. CONCLUSION: These results indicate that qMRI on the Unity MR-linac is feasible, accurate, and repeatable which is promising for treatment response monitoring and treatment plan adaptation based on daily qMRI.

Simultaneous acquisition of orthogonal plane cine imaging and isotropic 4D-MRI using super-resolution.

INTRODUCTION: Effective management of intrafraction motion is critical to the success of MR-guided radiation therapy (MR-gRT) of abdominal or thoracic tumors. Recent developments have proposed the use of cine MRI to monitor motion and 4D-MRI to aid in the reconstruction of dose actually delivered to patients. The present work aims to develop and perform preliminary testing of an imaging framework capable of simultaneously acquiring orthogonal plane cine imaging and isotropic resolution 4D-MRI volumes using super-resolution methods. METHODS: A pulse sequence was developed to acquire time-locked cine imaging in sagittal and coronal planes while additionally acquiring 4D-MRIs in both planes simultaneously. Isotropic resolution 4D-MRIs were reconstructed by combining information from the orthogonal volumes using super-resolution methods. This method was tested in phantoms and in liver cancer patients. RESULTS: Simultaneous cine imaging in sagittal and coronal planes allowed monitoring of respiratory motion and an accurate binning of concurrently acquired 4D imaging slices into the appropriate respiratory phases. The super-resolution reconstruction methods improved the resolution of the 4D-MRI along both of the low-resolution slice-select dimensions. CONCLUSIONS: The development and preliminary testing of an imaging framework capable of acquiring simultaneous orthogonal cine imaging and super-resolution 4D-MRI was performed. The promising results merit further investigation for use in dose reconstruction during MR-guided radiation therapy.

MRI commissioning of 1.5T MR-linac systems - a multi-institutional study.

BACKGROUND: Magnetic Resonance linear accelerator (MR-linac) systems represent a new type of technology that allows for online MR-guidance for high precision radiotherapy (RT). Currently, the first MR-linac installations are being introduced clinically. Since the imaging performance of these integrated MR-linac systems is critical for their application, a thorough commissioning of the MRI performance is essential. However, guidelines on the commissioning of MR-guided RT systems are not yet defined and data on the performance of MR-linacs are not yet available. MATERIALS & METHODS: Here we describe a comprehensive commissioning protocol, which contains standard MRI performance measurements as well as dedicated hybrid tests that specifically assess the interactions between the Linac and the MRI system. The commissioning results of four MR-linac systems are presented in a multi-center study. RESULTS: Although the four systems showed similar performance in all the standard MRI performance tests, some differences were observed relating to the hybrid character of the systems. Field homogeneity measurements identified differences in the gantry shim configuration, which was later confirmed by the vendor. CONCLUSION: Our results highlight the importance of dedicated hybrid commissioning tests and the ability to compare the machines between institutes at this very early stage of clinical introduction. Until formal guidelines and tolerances are defined the tests described in this study may be used as a practical guideline. Moreover, the multi-center results provide initial bench mark data for future MR-linac installations.

Simultaneous motion monitoring and truth-in-delivery analysis imaging framework for MR-guided radiotherapy.

Intrafraction motion (i.e. motion occurring during a treatment session) can play a pivotal role in the success of abdominal and thoracic radiation therapy. Hybrid magnetic resonance-guided radiotherapy (MR-gRT) systems have the potential to control for intrafraction motion. Recently, we introduced an MRI sequence capable of acquiring real-time cine imaging in two orthogonal planes (SOPI). We extend SOPI here to permit dynamic updating of slice positions in one-plane while keeping the other plane position fixed. In this implementation, cine images from the static plane are used for motion monitoring and as image navigators to sort stepped images in the other plane, producing dynamic 4D image volumes for use in dose reconstruction. A custom 3D-printed target, designed to mimic the pancreas and duodenum and filled with radiochromic FXG gel, was interfaced to the dynamic motion phantom. 4D-SOPI was acquired in a dynamic motion phantom driven by an actual patient respiratory waveform displaying amplitude/frequency variations and drifting and in a healthy volunteer. Unique 4D-MRI epochs were reconstructed from a time series of phantom motion. Dose from a static 4 cm × 15 cm field was calculated on each 4D respiratory phase bin and epoch image, scaled by the time spent in each bin, and then rigidly accumulated. The phantom was then positioned on an Elekta MR-Linac and irradiated while moving. Following irradiation, actual dose deposited to the FXG gel was determined by applying a R 1 versus dose calibration curve to R 1 maps of the phantom. The 4D-SOPI cine images produced a respiratory motion navigator that was highly correlated with the actual phantom motion (CC = 0.9981). The mean difference between the accumulated and measured dose inside the target was 4.4% of the maximum prescribed dose. These initial results demonstrate that 4D-SOPI is a promising imaging framework enabling simultaneous real-time motion monitoring and truth-in-delivery analysis for integrated MR-gRT systems.