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Motion is problematic during radiotherapy as it could lead to potential underdosage of the tumor, and/or overdosage in organs-at-risk. A solution is adaptive radiotherapy guided by magnetic resonance imaging (MRI). MRI allows for imaging of target volumes and organs-at-risk before and during treatment delivery with superb soft tissue contrast in any desired orientation, enabling motion management by means of (real-time) adaptive radiotherapy. The noise navigator, which is independent of the MR signal, could serve as a secondary motion detection method in synergy with MR imaging. The feasibility of respiratory motion detection by means of the noise navigator was demonstrated previously. Furthermore, from electromagnetic simulations we know that the noise navigator is sensitive to tissue displacement and thus could in principle be used for the detection of various types of motion. In this study we demonstrate the detection of various types of motion for three anatomical use cases of MRI-guided radiotherapy, i.e. torso (bulk movement and variable breathing), head-and-neck (swallowing) and cardiac. Furthermore, it is shown that the noise navigator can detect bulk movement, variable breathing and swallowing on a hybrid 1.5 T MRI-linac system. Cardiac activity detection through the noise navigator seems feasible in an MRI-guided radiotherapy setting, but needs further optimization. The noise navigator is a versatile and fast (millisecond temporal resolution) motion detection method independent of MR signal that could serve as an independent verification method to detect the occurrence of motion in synergy with real-time MRI-guided radiotherapy.

Respiratory-correlated 4D-MRI can characterize respiratory-induced motion of tumors and organs-at-risk for radiotherapy treatment planning and is a necessity for image guidance of moving tumors treated on an MRI-linac. Essential for 4D-MRI generation is a robust respiratory surrogate signal. We investigated the feasibility of the noise navigator as respiratory surrogate signal for 4D-MRI generation. The noise navigator is based on the respiratory-induced modulation of the thermal noise variance measured by the receive coils during MR acquisition and thus is inherently present and synchronized with MRI data acquisition. Additionally, the noise navigator can be combined with any rectilinear readout strategy (e.g. radial and cartesian) and is independent of MR image contrast and imaging orientation. For radiotherapy applications, the noise navigator provides a robust respiratory signal for patients scanned with an elevated coil setup. This is particularly attractive for widely used cartesian sequences where currently a non-interfering self-navigation means is lacking for MRI-based simulation and MRI-guided radiotherapy. The feasibility of 4D-MRI generation with the noise navigator as respiratory surrogate signal was demonstrated for both cartesian and radial readout strategies in radiotherapy setup on four healthy volunteers and two radiotherapy patients on a dedicated 1.5 T MRI scanner and two radiotherapy patients on a 1.5 T MRI-linac system. Moreover, the respiratory-correlated 4D-MR images showed liver motion comparable to a reference 2D cine MRI series for the volunteers. For 2D cartesian cine MRI acquisitions, both the noise navigator and respiratory bellows were benchmarked against an image navigator. Respiratory phase detection based on the noise navigator agreed 1.4 times better with the image navigator than the respiratory bellows did. For a 3D Stack-of-Stars acquisitions, the noise navigator was compared to radial self-navigation and a 1.7 times higher respiratory phase detection agreement was observed than for the respiratory bellows compared to radial self-navigation.

Hybrid MR-linac systems enable intrafraction motion monitoring during radiation therapy. Since time-resolved 3D MRI is still challenging, various motion models have been developed that rely on time-resolved 2D imaging. Continuous validation of these models is important for accurate dose accumulation mapping. In this study we used 2D simultaneous multislice (SMS) imaging to improve the PCA-based motion modeling method developed previously (Stemkens et al 2016 Phys. Med. Biol. 61 5335-55). From the additional simultaneously acquired slices, several independent motion models could be generated, which allowed for an assessment of the sensitivity of the motion model to the location of the time-resolved 2D slices. Additionally, the best model could be chosen at every time-point, increasing the method's robustness. Imaging experiments were performed in six healthy volunteers using three simultaneous slices, which generated three independent models per volunteer. For each model the motion traces of the liver tip and both kidneys were estimated. We found that the location of the 2D slices influenced the model's error in five volunteers significantly with a p -value  <0.05, and that selecting the best model at every time-point can improve the method. This allows for more accurate and robust motion characterization in MR-guided radiotherapy.

For successful abdominal radiotherapy it is crucial to have a clear tumor definition and an accurate characterization of the motion. While dynamic contrast-enhanced (DCE) MRI aids tumor visualization, it is often hampered by motion artifacts. 4D-MRI characterizes this motion, but often lacks the contrast to clearly visualize the tumor. This dual requirement is challenging due to time constraints. Here, we propose combining both into a single acquisition by reconstructing the data in various ways in order to achieve both high spatio-temporal resolution DCE-MRI and accurate 4D-MRI motion estimates. A 5 min T 1 -weigthed DCE acquisition was collected in five renal-cell carcinoma patients and simulated in a digital phantom. Data were acquired continuously using a 3D golden angle radial stack-of-stars acquisition. This enabled three types of reconstruction; (1) a high spatio-temporal resolution DCE time series, (2) a 5D reconstruction and (3) a contrast-enhanced 4D-MRI for motion characterization. Motion extracted from the 4D- and 5D-MRI was compared with a separately acquired 4D-MRI and additional 2D cine MR imaging. Simulations on XCAT showed that 5D reconstructions severely underestimated motion ([Formula: see text]), whereas contrast-enhanced 4D-MRI only underestimated motion by [Formula: see text]. This was confirmed in the in vivo data where motion of the contrast-enhanced 4D-MRI was approximately [Formula: see text] smaller than the motion in the 2D cine MRI (5.8 mm versus 6.5 mm), but equal to a separately acquired 4D-MRI (5.8 mm versus 5.9 mm). 5D reconstructions underestimated the motion by more than [Formula: see text], but minimized respiratory-induced blurring in the contrast enhanced images. DCE time-series demonstrated clear tumor visualization and contrast enhancement throughout the entire field-of-view. DCE- and 4D-MRI can be integrated into a single acquisition that enables different reconstructions with complementary information for abdominal radiotherapy planning and, in an MRI-guided treatment, precise motion information, input for motion models, and rapid feedback on the contrast enhancement.

Online adaptive MR-guided radiation therapy improves treatment quality at the expense of considerable longer treatment time. The treatment lengthening partially originates from the preparatory (pre-beam) MR imaging required to encode all the information needed for contour propagation, contour adaptation and replanning. MRI requires several minutes of scan time before the encoded information is converted to usable images, which results in long idle times before the first clinical tasks are performed. In this study we propose a novel imaging sequence, called MR-RIDDLE, that reduces the idle time and therefore speeds-up the workflow in online MR-guided radiation therapy. MR-RIDDLE enables multiresolution image reconstruction to commence during data acquisition where low resolution images are available within one minute, after which the data collection continuous for subsequent high-resolution image updates. We demonstrate that the low resolution images can be used to accurately propagate contours from the pre-treatment scan. For abdominothoracic tumours MR-RIDDLE inherently captures a motion-blurred representation of the mid-position, which we were able to deblur using a combination of an internal motion surrogate and auto-adaptive soft-gating filters. Our results demonstrate that MR-RIDDLE provides a robust, flexible and time-efficient strategy for pre-beam imaging, even for cases with large respiratory movements or baseline shifts within the acquisition. We anticipate that this novel concept of parallelising the MR imaging and the clinical tasks has the potential to considerably speed-up and streamline the online MR-guided radiation therapy workflow.

Purpose: One of the major challenges in stereotactic body radiation therapy (SBRT) of renal cell carcinoma is internal motion during treatment. Previous literature has aimed to mitigate the effects of motion by expanding the treatment margins or respiratory tracking. Online magnetic resonance imaging (MRI)-guided radiation therapy has the potential to further improve the treatment of renal cell carcinoma by direct visualization of the tumor during treatment. The efficacy of 2 motion management techniques were assessed: tumor trailing and respiratory tracking. The simulation of a single-fraction, MRI-based SBRT was performed to quantify intrafraction motion and assess the efficacy of the different motion management strategies., Methods and Materials: Fifteen patients were included in the study. At the beginning and end of the scanning protocol, 2 cine-MRI scans were acquired to assess cyclic respiratory motion. In addition, 3-dimensional spoiled gradient echo scans were acquired at 4 different time points to assess the slow drifts over 25 minutes. The systematic and random errors owing to intrafraction drift were calculated, as well as the random error induced by respiratory motion. The motion margins were calculated for tumor trailing and respiratory tracking and compared with the margin when no motion compensation would be performed to assess the relative efficacy of each technique., Results: The largest respiratory tumor motion was observed along the caudo-cranial direction with a median 95% maximum amplitude of approximately 12 mm. Σ DRIFT , σ DRIFT , and σ RESP were determined to be 1.0 mm 1.8 mm, and 3.8 mm, respectively. Without mechanical immobilization, intrafraction drift accounted for 75% of the total intrafraction motion margin for online midposition-based SBRT treatments., Conclusions: The contribution of intrafraction drift to the total internal motion margin is much larger than periodic respiratory motion. This makes tumor trailing a viable option to consider on the MRI linac because it allows for 3-dimensional MRI acquisitions during beam delivery, which simplifies the introduction of new techniques, such as dose accumulation and online intrafraction replanning., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To develop and evaluate a combined motion-assisted/gated MRHIFU heating strategy designed to accelerate the treatment procedure by reducing the required number of sonications to ablate a target volume in the pancreas. Methods: A planning method for combined motion-assisted/gated MRHIFU using 4D-MRI and motion characterization is introduced. Six healthy volunteers underwent 4D-MRI for target motion characterization on a 3.0-T clinical scanner. Using displacement patterns, simulations were performed for all volunteers for three sonication approaches: gated, combined motion-assisted/gated, and static. The number of sonications needed to ablate the pancreas head was compared. The influence of displacement amplitude and target volume size was investigated. Spherical target volumes (8, 15, 20 and 34 mL) and displacement amplitudes ranging from 5 to 25 mm were evaluated. For this case, the number of sonications required to ablate the whole target was determined. Results: The number of required sonications was lowest for a static target, 62 on average (range 49-78). The gated approach required most sonications, 126 (range 97-159). The combined approach was almost as efficient as the hypothetical static case, with an average of 78 (range 53-123). Simulations showed that with a 5-mm displacement amplitude, the target could be treated by making use of motion-assisted MRHIFU sonications only. In that case, this approach allowed the lowest number of sonication, while for 10 mm and above, the number of required sonications increased. Conclusion: The use of a combined motion-assisted/gated MRHIFU strategy may accelerate tumor ablation in the pancreas when respiratory-induced displacement amplitudes are between 5 and 10 mm.

Magnetic resonance imaging (MRI) is increasingly being used in the radiotherapy workflow because of its superior soft tissue contrast and high flexibility in contrast. In addition to anatomical and functional imaging, MRI can also be used to characterize the physiologically induced motion of both the tumor and organs-at-risk. Respiratory-correlated 4D-MRI has gained large interest as an alternative to 4D-CT for the characterization of respiratory motion throughout the thorax and abdomen. These 4D-MRI data sets consist of three spatial dimensions and the respiratory phase or amplitude over the fourth dimension (opposed to time-resolved 4D-MRI that represents time in the fourth dimension). Over the last 15 years numerous methods have been presented in literature. This review article provides a comprehensive overview of the various 4D-MRI techniques, and describes the differences in MRI data acquisition and 4D data set generation from a methodological point of view. The current status and future perspective of these techniques are highlighted, and the requirements for safe introduction into the clinic (e.g. method validation) are discussed.

Non-Cartesian magnetic resonance imaging (MRI) sequences have shown great promise for abdominal examination during free breathing, but break down in the presence of bulk patient motion (i.e. voluntary or involuntary patient movement resulting in translation, rotation or elastic deformations of the body). This work describes a data-consistency-driven image stabilization technique that detects and excludes bulk movements during data acquisition. Bulk motion is identified from changes in the signal intensity distribution across different elements of a multi-channel receive coil array. A short free induction decay signal is acquired after excitation and used as a measure to determine alterations in the load distribution. The technique has been implemented on a clinical MR scanner and evaluated in the abdomen. Six volunteers were scanned and two radiologists scored the reconstructions. To show the applicability to other body areas, additional neck and knee images were acquired. Data corrupted by bulk motion were successfully detected and excluded from image reconstruction. An overall increase in image sharpness and reduction of streaking and shine-through artifacts were seen in the volunteer study, as well as in the neck and knee scans. The proposed technique enables automatic real-time detection and exclusion of bulk motion during MR examinations without user interaction. It may help to improve the reliability of pediatric MRI examinations without the use of sedation., (© 2017 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

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.

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.

Respiratory motion introduces substantial uncertainties in abdominal radiotherapy for which traditionally large margins are used. The MR-Linac will open up the opportunity to acquire high resolution MR images just prior to radiation and during treatment. However, volumetric MRI time series are not able to characterize 3D tumor and organ-at-risk motion with sufficient temporal resolution. In this study we propose a method to estimate 3D deformation vector fields (DVFs) with high spatial and temporal resolution based on fast 2D imaging and a subject-specific motion model based on respiratory correlated MRI. In a pre-beam phase, a retrospectively sorted 4D-MRI is acquired, from which the motion is parameterized using a principal component analysis. This motion model is used in combination with fast 2D cine-MR images, which are acquired during radiation, to generate full field-of-view 3D DVFs with a temporal resolution of 476 ms. The geometrical accuracies of the input data (4D-MRI and 2D multi-slice acquisitions) and the fitting procedure were determined using an MR-compatible motion phantom and found to be 1.0-1.5 mm on average. The framework was tested on seven healthy volunteers for both the pancreas and the kidney. The calculated motion was independently validated using one of the 2D slices, with an average error of 1.45 mm. The calculated 3D DVFs can be used retrospectively for treatment simulations, plan evaluations, or to determine the accumulated dose for both the tumor and organs-at-risk on a subject-specific basis in MR-guided radiotherapy.

The purpose of this study is to investigate the feasibility of using internal respiratory (IR) surrogates to sort four-dimensional (4D) magnetic resonance (MR) images. The 4D MR images were constructed by acquiring fast 2D cine MR images sequentially, with each slice scanned for more than one breathing cycle. The 4D volume was then sorted retrospectively using the IR signal. In this study, we propose to use multiple low-frequency components in the Fourier space as well as the anterior body boundary as potential IR surrogates. From these potential IR surrogates, we used a clustering algorithm to identify those that best represented the respiratory pattern to derive the IR signal. A study with healthy volunteers was performed to assess the feasibility of the proposed IR signal. We compared this proposed IR signal with the respiratory signal obtained using respiratory bellows. Overall, 99% of the IR signals matched the bellows signals. The average difference between the end inspiration times in the IR signal and bellows signal was 0.18 s in this cohort of matching signals. For the acquired images corresponding to the other 1% of non-matching signal pairs, the respiratory motion shown in the images was coherent with the respiratory phases determined by the IR signal, but not the bellows signal. This suggested that the IR signal determined by the proposed method could potentially correct the faulty bellows signal. The sorted 4D images showed minimal mismatched artefacts and potential clinical applicability. The proposed IR signal therefore provides a feasible alternative to effectively sort MR images in 4D.

Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes., Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously., Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor., Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)