LETTER • OPEN ACCESSFirst patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, highfield MRI guided radiotherapy treatment AbstractThe integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac.Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while Letter Institute of Physics and Engineering in MedicineOriginal content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. 3 Author to whom any correspondence should be addressed. the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm.In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

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.

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 Â 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

The hybrid MRI-radiotherapy machines, like the MR-linac (Elekta AB, Stockholm, Sweden) installed at the UMC Utrecht (Utrecht, The Netherlands), will be able to provide real-time patient imaging during treatment. In order to take advantage of the system's capabilities and enable online adaptive treatments, a new generation of software should be developed, ranging from motion estimation to treatment plan adaptation. In this work we present a proof of principle adaptive pipeline designed for high precision stereotactic body radiation therapy (SBRT) suitable for sites affected by respiratory motion, like renal cell carcinoma (RCC). We utilized our research MRL treatment planning system (MRLTP) to simulate a single fraction 25 Gy free-breathing SBRT treatment for RCC by performing inter-beam replanning for two patients and one volunteer. The simulated pipeline included a combination of (pre-beam) 4D-MRI and (online) 2D cine-MR acquisitions. The 4DMRI was used to generate the mid-position reference volume, while the cine-MRI, via an in-house motion model, provided three-dimensional (3D) deformable vector fields (DVFs) describing the anatomical changes during treatment. During the treatment fraction, at an inter-beam interval, the mid-position volume of the patient was updated and the delivered dose was accurately reconstructed on the underlying motion calculated by the model. Fast online replanning, targeting the latest anatomy and incorporating the previously delivered dose was then simulated with MRLTP. The adaptive treatment was compared to a conventional mid-position SBRT plan with a 3 mm planning target volume margin reconstructed on the same motion trace. We demonstrate that our system produced tighter dose distributions and thus spared the healthy tissue, while delivering more dose to the target. The pipeline was able to account for baseline variations/drifts that occurred during treatment ensuring target coverage at the end of the treatment fraction.

Recently, multileaf collimator (MLC)-tracking has been technically and clinically demonstrated showing promising improvements of radiotherapy of mobile sites. Furthermore, magnetic resonance imaging (MRI)-guided treatments have shown to provide superior targetting performance due to on-line soft-tissue imaging. Hitherto, the combination of MLC-tracking and MRI has not been investigated using clinically released hardware. In this note we aim to describe the technical feasibilty of such a combination on a clinically operating MRI-linac. The MLC-tracking system is characterized by quantifying the latencies and geometric errors produced by the system. In order to reach optimization recommendations, the tracking system was first characterized using a quasi-ideal position sensor, isolating the performance of the MLC only. Subsequently, the analysis was repeated using real-time MRI as the positioning source for the MLC. For the isolated MLC, we found latencies of 20.67 ms and minimal overshooting behaviour. The latencies for MRI-guidance were 347.45 ms at 4 Hz imaging and 204 ms at 8 Hz. We showed that MLC-tracking on the Elekta Unity using integrated MRI is technically supported and feasible. The isolated analysis of the MLC demonstrated the negligible contribution of the MLC in MRI-guided tracking. The latency and geometric errors caused by the sampling properties of MRI exceed the MLC-related errors by several factors. Most gain for real-time MRI-based adaptive radiotherapy can therefore be realized by optimizing and accelerating the MRI acquisition process.

Hybrid MR-linac systems can use fast dynamic MR sequences for tumor tracking and adapt the radiation treatment in real-time. For this the imaging latency must be as short as possible. This work describes how different acquisition parameters influence this latency. First, the latency was measured for Cartesian readouts with phase encode orderings linear, reverse-linear, and high-low. Second, the latency was measured for radial readouts with linear and golden angle profile orderings. To reduce the latency, a spatio-temporal (k-t) filter that suppresses the k-space center of earlier acquired spokes was implemented for the golden angle sequence. For Cartesian readouts a high-low ordering achieved a three times lower latency compared to a linear ordering with our sampling parameters. For radial readouts the filter was able to reduce the acquisition latency from half the acquisition time to a quarter of the acquisition time. The filter did not compromise the signal-to-noise ratio and the artifact power.

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to [Formula: see text] of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial.Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant.In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur.The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions.In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose.Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  -2.3-1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  -2.5 to 1.9 Gy could be traced back.