Proof-of-concept delivery of intensity modulated arc therapy on the Elekta Unity 1.5 T MR-linac

In this work we present the first delivery of intensity modulated arc therapy on the Elekta Unity 1.5 T MR-linac. The machine's current intensity modulated radiation therapy based control system was modified suitably to enable dynamic delivery of radiation, for the purpose of exploring MRI-guided radiation therapy adaptation modes in a research setting. The proof-of-concept feasibility was demonstrated by planning and delivering two types of plans, each investigating the performance of different parts of a dynamic treatment. A series of fixed-speed arc plans was used to show the high-speed capabilities of the gantry during radiation, while several fully modulated prostate plans-optimised following the volumetric modulated arc therapy approach-were delivered in order to establish the performance of its multi-leaf collimator and diaphragms. These plans were delivered to Delta4 Phantom+ MR and film phantoms passing the clinical quality assurance criteria used in our clinic. In addition, we also performed some initial MR imaging experiments during dynamic therapy, demonstrating that the impact of radiation and moving gantry/collimator components on the image quality is negligible. These results show that arc therapy is feasible on the Elekta Unity system. The machine's high performance components enable dynamic delivery during fast gantry rotation and can be controlled in a stable fashion to deliver fully modulated plans

Intrafraction motion analysis in online adaptive radiotherapy for esophageal cancer

Intrafraction motion during magnetic resonance (MR)-guided dose delivery of esophageal cancer tumors was retrospectively analyzed. Deformable image registration of cine-MR series resulted in gross tumor volume motion profiles in all directions, which were subsequently filtered to isolate respiratory and drift motion. A large variability in intrafraction motion patterns was observed between patients. Median 95% peak-to-peak motion was 7.7 (3.7 - 18.3) mm, 2.1 (0.7 - 5.7) mm and 2.4 (0.5 - 5.6) mm in cranio-caudal, left-right and anterior-posterior directions, relatively. Furthermore, intrafraction drift was generally modest (<5mm). A patient specific approach could lead to very small margins (<3mm) for most patients

Fast and accurate deformable contour propagation for intra-fraction adaptive magnetic resonance-guided prostate radiotherapy

To facilitate full intra-fraction adaptive MR-guided radiotherapy, accurate contour propagation is needed. We aimed to assess the clinical usability of intra-fraction propagated contours by a deformable image registration algorithm in ten prostate cancer patients. Two observers judged the contours on need for manual adaptation and feasibility of adapting contours within 3 min. CTV and bladder contours needed none or only minor editing in most cases (≥ 97%), whereas rectum contours needed more extensive editing in 12-23%. Nevertheless, adaptation times were < 3 min for ≥ 93% of the cases. This paves the way for exploring adaptive workflows using intra-fraction deformable contour propagation

Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup

Improving the imaging performance of the 1.5 T MR-linac using a flexible, 32-channel, on-body receive array

High impedance coils (HICs) are suitable as a building block of receive arrays for MRI-guided radiotherapy (MRIgRT) as HICs do not require radiation-attenuating capacitors and dense support materials. Recently, we proved the feasibility of using HICs to create a radiation transparent (i.e. radiolucent) window. In this work, we constructed a fully functional 32-channel array based on this design. The anterior element is flexible and follows the shape of the subject, while the posterior element is rigid to support the subject. Both elements feature a 2 × 8 channel layout. Here, we discuss the construction process and characterize the array's radiolucency and imaging performance. The dosimetric impact of the array was quantified by assessing the surface dose increase and attenuation of a single beam. The imaging performance of the prototype was compared to the clinical array in terms of visual appearance, signal-to-noise ratio (SNR), and acceleration performance, both in phantom and in-vivo measurements. Dosimetry measurements showed that on-body placement changed the anterior and posterior surface dose by +3% and -16% of the dose maximum. Attenuation under the anterior support materials and conductors was 0.3% and ≤1.5%, respectively. Phantom and in-vivo imaging with this array demonstrated an improvement of the SNR at the surface and the image quality in general. Simultaneous irradiation did not affect the SNR. G-factors were reduced considerably and clinically used sequences could be accelerated by up to 45%, which would greatly reduce pre-beam imaging times. Finally, the maximally achievable temporal resolution of abdominal 3D cine imaging was improved to 1.1 s, which was > 5 × faster than could be achieved with the clinical array. This constitutes a big step towards the ability to resolve respiratory motion in 3D. In conclusion, the proposed 32-channel array is compatible with MRIgRT and can significantly reduce scan times and/or improve the image quality of all on-line scans

Evaluation of daily online contour adaptation by radiation therapists for prostate cancer treatment on an MRI-guided linear accelerator

Background and purpose: Magnetic resonance (MR)-guided linear accelerator (MR-Linac) systems have changed radiotherapy workflows. The addition of daily online contour adaptation allows for higher precision treatment, but also increases the workload of those involved. We train radiation therapists (RTTs) to perform daily online contour adaptation for MR-Linac treatment of prostate cancer (PCa) patients. The purpose of this study was to evaluate these prostate contours by performing an interfraction and interobserver analysis. Materials and methods: Clinical target volume (CTV) contours generated online by RTTs from 30 low-intermediate risk PCa patients, treated with 5x7.25 Gy, were used. Two physicians (Observers) judged the RTTs contours and performed adaptations when necessary. Interfraction relative volume differences between the first and the subsequent fractions were calculated for the RTTs, Observer 1, and Observer 2. Additionally, interobserver dice's similarity coefficient (DSC) for fraction 2-5 was calculated with the RTTs- and physician-adapted contours. Clinical acceptability of the RTTs contours was judged by a third observer. Results: Mean (SD) online contour adaptation time was 12.6 (±3.8) minutes and overall median (interquartile range [IQR]) relative volume difference was 9.3% (4.4-13.0). Adaptations by the observers were mostly performed at the apex and base of the prostate. Median (IQR) interobserver DSC between RTTs and Observer 1, RTTs and Observer 2, and Observer 1 and 2 was 0.99 (0.98-1.00), 1.00 (0.98-1.00), and 1.00 (0.99-1.00), respectively. Contours were acceptable for clinical use in 113 (94.2%) fractions. Dose-volume histogram (DVH) analysis showed significant CTV underdosage for one of the seven identified outliers. Conclusion: Daily online contour adaptation by RTTs is clinically feasible for MR-Linac treatment of PCa

Clinical application of a sub-fractionation workflow for intrafraction re-planning during prostate radiotherapy treatment on a 1.5 Tesla MR-Linac: A practical method to mitigate intrafraction motion

BACKGROUND: Intrafraction motion during radiotherapy limits margin reduction and dose escalation. Magnetic resonance (MR)-guided linear accelerators (MR-Linac) have emphasised this issue by enabling intrafraction imaging. We present and clinically apply a new workflow to counteract systematic intrafraction motion during MR-guided stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: With the sub-fractionation workflow, the daily dose is delivered in multiple sequential parts (sub-fractions), each adapted to the latest anatomy. As each sub-fractionation treatment plan complies with the dose constraints, no online dose accumulation is required. Imaging and treatment planning are executed in parallel with dose delivery to minimise dead time, enabling an efficient workflow. The workflow was implemented on a 1.5 T MR-Linac and applied in 15 prostate cancer (PCa) patients treated with 5 × 7.25 Gy in two sub-fractions of 3.625 Gy (10 × 3.625 Gy in total). Intrafraction clinical target volume (CTV) motion was determined and compared to a workflow with single-plan delivery. Furthermore, required planning target volume (PTV) margins were determined. RESULTS: Average on-table time was 42.7 min. Except for two fractions, all fractions were delivered within 60 min. Average intrafraction 3D CTV displacement (±standard deviation) was 1.1 mm (± 0.7) with the sub-fractionation workflow, whereas this was up to 3.5 mm (± 2.4) without sub-fractionation. Calculated PTV margins required with sub-fractionation were 1.0 mm (left-right), 2.4 mm (cranial-caudal), and 2.6 mm (anterior-posterior). CONCLUSION: Feasibility of the sub-fractionation workflow was demonstrated in 15 PCa patients treated with two sub-fractions on a 1.5 T MR-Linac. The workflow allows for significant PTV margin reduction in these patients by reducing systematic intrafraction motion during SBRT

Acceptance procedure for the linear accelerator component of the 1.5 T MRI-linac

Purpose: To develop and implement an acceptance procedure for the new Elekta Unity 1.5 T MRI-linac. Methods: Tests were adopted and, where necessary adapted, from AAPM TG106 and TG142, IEC 60976 and NCS 9 and NCS 22 guidelines. Adaptations were necessary because of the atypical maximum field size (57.4 × 22 cm), FFF beam, the non-rotating collimator, the absence of a light field, the presence of the 1.5 T magnetic field, restricted access to equipment within the bore, fixed vertical and lateral table position, and the need for MR image to MV treatment alignment. The performance specifications were set for stereotactic body radiotherapy (SBRT). Results: The new procedure was performed similarly to that of a conventional kilovoltage x-ray (kV) image guided radiation therapy (IGRT) linac. Results were acquired for the first Unity system. Conclusions: A comprehensive set of tests was developed, described and implemented for the MRI-linac. The MRI-linac met safety requirements for patients and operators. The system delivered radiation very accurately with, for example a gantry rotation locus of isocenter of radius 0.38 mm and an average MLC absolute positional error of 0.29 mm, consistent with use for SBRT. Specifications for clinical introduction were met

Deep learning-based image reconstruction and motion estimation from undersampled radial k-space for real-time MRI-guided radiotherapy.

To enable magnetic resonance imaging (MRI)-guided radiotherapy with real-time adaptation, motion must be quickly estimated with low latency. The motion estimate is used to adapt the radiation beam to the current anatomy, yielding a more conformal dose distribution. As the MR acquisition is the largest component of latency, deep learning (DL) may reduce the total latency by enabling much higher undersampling factors compared to conventional reconstruction and motion estimation methods. The benefit of DL on image reconstruction and motion estimation was investigated for obtaining accurate deformation vector fields (DVFs) with high temporal resolution and minimal latency. 2D cine MRI acquired at 1.5 T from 135 abdominal cancer patients were retrospectively included in this study. Undersampled radial golden angle acquisitions were retrospectively simulated. DVFs were computed using different combinations of conventional- and DL-based methods for image reconstruction and motion estimation, allowing a comparison of four approaches to achieve real-time motion estimation. The four approaches were evaluated based on the end-point-error and root-mean-square error compared to a ground-truth optical flow estimate on fully-sampled images, the structural similarity (SSIM) after registration and time necessary to acquire k-space, reconstruct an image and estimate motion. The lowest DVF error and highest SSIM were obtained using conventional methods up to [Formula: see text]. For undersampling factors [Formula: see text], the lowest DVF error and highest SSIM were obtained using conventional image reconstruction and DL-based motion estimation. We have found that, with this combination, accurate DVFs can be obtained up to [Formula: see text] with an average root-mean-square error up to 1 millimeter and an SSIM greater than 0.8 after registration, taking 60 milliseconds. High-quality 2D DVFs from highly undersampled k-space can be obtained with a high temporal resolution with conventional image reconstruction and a deep learning-based motion estimation approach for real-time adaptive MRI-guided radiotherapy

Development and internal validation of multivariable prediction models for biochemical failure after MRI-guided focal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

Background and purpose: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up. Materials and methods: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified. Results: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, pre-salvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2). Conclusion: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre- and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT