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Purpose MR-guided radiotherapy has different requirements for the images than diagnostic radiology, thus requiring development of novel imaging sequences. MRI simulation is an excellent tool for optimizing these new sequences; however, currently available software does not provide all the necessary features. In this paper, we present a digital framework for testing MRI sequences that incorporates anatomical structure, respiratory motion, and realistic presentation of MR physics. Methods The extended Cardiac-Torso (XCAT) software was used to create T1 , T2 , and proton density maps that formed the anatomical structure of the phantom. Respiratory motion model was based on the XCAT deformation vector fields, modified to create a motion model driven by a respiration signal. MRI simulation was carried out with JEMRIS, an open source Bloch simulator. We developed an extension for JEMRIS, which calculates the motion of each spin independently, allowing for deformable motion. Results The performance of the framework was demonstrated through simulating the acquisition of a two-dimensional (2D) cine and demonstrating expected motion ghosts from T2 weighted spin echo acquisitions with different respiratory patterns. All simulations were consistent with behavior previously described in literature. Simulations with deformable motion were not more time consuming than with rigid motion. Conclusions We present a deformable four-dimensional (4D) digital phantom framework for MR sequence development. The framework incorporates anatomical structure, realistic breathing patterns, deformable motion, and Bloch simulation to achieve accurate simulation of MRI. This method is particularly relevant for testing novel imaging sequences for the purpose of MR-guided radiotherapy in lungs and abdomen.

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = − 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT. Electronic supplementary material The online version of this article (doi:10.1007/s10439-020-02697-5) contains supplementary material, which is available to authorized users.

Highlights • Detailed RILD evolution described by objective radiological and pulmonary function measures. • RILD is associated with volume loss of the treated lung and contralateral lung hyperinflation. • Objective radiological findings might differentiate subjects with early versus late RILD. • Most patients developed progressive lung damage, even when the early phase is absent/mild. • Pre-RT lung function and RT dosimetry may identify subjects at increased risk of developing RILD., Background and purpose Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. Materials and methods CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. Results FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3–6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6–24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30–0.40, p = 0.01–0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. Conclusions CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD.

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as ‘acceptable’, ‘minor disagreement’ or ‘major disagreement’. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

Objective. Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence. Approach. We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans’ objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED95 (BED delivered to 95% of the target volume) values. Main results. When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours–days) while typically reaching within 1.2% (0.02–2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments. Significance. We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality.

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung computed tomography (CT) scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12 month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for three additional follow-up timepoints up to 48 months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection.

Objective: The aim of this study was to evaluate the current status of the clinical use of deformable image registration (DIR) in radiotherapy and to gain an understanding of the challenges faced by centres in clinical implementation of DIR, including commissioning and quality assurance (QA), and to determine the barriers faced. The goal was to inform whether additional guidance and QA tools were needed. Methods: A survey focussed on clinical use, metrics used, how centres would like to use DIR in the future and challenges faced, was designed and sent to 71 radiotherapy centres in the UK. Data were gathered specifically on which centres we using DIR clinically, which applications were being used, what commissioning and QA tests were performed, and what barriers were preventing the integration of DIR into the clinical workflow. Centres that did not use DIR clinically were encouraged to fill in the survey and were asked if they have any future plans and in what timescale. Results: 51 out of 71 (70%) radiotherapy centres responded. 47 centres reported access to a commercial software that could perform DIR. 20 centres already used DIR clinically, and 22 centres had plans to implement an application of DIR within 3 years of the survey. The most common clinical application of DIR was to propagate contours from one scan to another (19 centres). In each of the applications, the types of commissioning and QA tests performed varied depending on the type of application and between centres. Some of the key barriers were determining when a DIR was satisfactory including which metrics to use, and lack of resources. Conclusion: The survey results highlighted that there is a need for additional guidelines, training, better tools for commissioning DIR software and for the QA of registration results, which should include developing or recommending which quantitative metrics to use. Advances in knowledge: This survey has given a useful picture of the clinical use and lack of use of DIR in UK radiotherapy centres. The survey provided useful insight into how centres commission and QA DIR applications, especially the variability among centres. It was also possible to highlight key barriers to implementation and determine factors that may help overcome this which include the need for additional guidance specific to different applications, better tools and metrics.

Respiratory motion correction is beneficial in positron emission tomography. Different strategies for handling attenuation correction in conjunction with motion correction exist. In clinical practice, usually a single attenuation map is available, derived from computed tomography in one respiratory state. This can introduce an unwanted bias (through misaligned anatomy) into the motion correction algorithm. This paper builds upon previous work which suggested that non-attenuation corrected data was suitable for motion estimation, through the use of motion models, if time-of-flight data are available. Here, the previous work is expanded upon by incorporating attenuation correction in an iterative process. Non-attenuation corrected volumes are reconstructed using ordered subset expectation maximisation and used as input for motion model estimation. A single attenuation map is then warped to the volumes, using the motion model, the volumes are attenuation corrected, after which another motion estimation and correction cycle is performed. For validation, 4-Dimensional Extended Cardiac Torso simulations are used, for one bed position, with a field of view including the base of the lungs and the diaphragm. The output from the proposed method is evaluated against a non-motion corrected reconstruction of the same data visually, using a profile as well as standardised uptake value analysis. Results indicate that motion correction of inter-respiratory cycle motion is possible with this method, while accounting for attenuation deformation.

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible.

Purpose Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long-term radiation-induced lung damage (RILD). However, there are still no objective criteria to quantify RILD, leading to variable reporting across centers and trials. We propose a set of objective imaging biomarkers for quantifying common radiologic findings observed 12 months after lung cancer radiation therapy. Methods and Materials Baseline and 12-month computed tomography (CT) scans of 27 patients from a phase 1/2 clinical trial of isotoxic chemoradiation were included in this study. To detect and measure the severity of RILD, 12 quantitative imaging biomarkers were developed. The biomarkers describe basic CT findings, including parenchymal change, volume reduction, and pleural change. The imaging biomarkers were implemented as semiautomated image analysis pipelines and were assessed against visual assessment of the occurrence of each change. Results Most of the biomarkers were measurable in each patient. The continuous nature of the biomarkers allows objective scoring of severity for each patient. For each imaging biomarker, the cohort was split into 2 groups according to the presence or absence of the biomarker by visual assessment, testing the hypothesis that the imaging biomarkers were different in the 2 groups. All features were statistically significant except for rotation of the main bronchus and diaphragmatic curvature. Most of the biomarkers were not strongly correlated with each other, suggesting that each of the biomarkers is measuring a separate element of RILD pathology. Conclusions We developed objective CT-based imaging biomarkers that quantify the severity of radiologic lung damage after radiation therapy. These biomarkers are representative of typical radiologic findings of RILD.

In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed.This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.

Purpose To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. Material and methods Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. Results Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. Conclusions Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

Respiratory motion reduces image quality in Positron Emission Tomography (PET). Unless gated Computed Tomography (CT) or Magnetic Resonance (MR) data are available, motion correction relies on registration of the PET data. To avoid mis-registration due to attenuation mismatches, most existing methods rely on pair-wise registration of Non-Attenuation Corrected (NAC) PET volumes. This is a challenging problem due to the low contrast and high noise of these volumes. This paper investigates the possibility of using motion models for respiratory motion correction in PET, and in particular whether incorporating Time-of-Flight (TOF) information increases the accuracy of the motion models derived from the NAC reconstructed images. 4D Extended Cardiac-Torso (XCAT) phantom simulations are used for one bed position with a field of view including the base of the lungs and the diaphragm. A TOF resolution of 375ps is used. NAC images are reconstructed using Orded SubSet Expectation Maximisation (OSEM) and used as input for motion model estimation. Different motion models are compared using the original XCAT input volumes. The results indicate that TOF improves the accuracy of the motion model considerably.

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF’s recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF’s integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors. This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.

Breathing motion is challenging for radiotherapy planning and delivery. This requires advanced four-dimensional (4D) imaging and motion mitigation strategies and associated validation tools with known deformations. Numerical phantoms such as the XCAT provide reproducible and realistic data for simulation-based validation. However, the XCAT generates partially inconsistent and non-invertible deformations where tumours remain rigid and structures can move through each other. We address these limitations by post-processing the XCAT deformation vector fields (DVF) to generate a breathing phantom with realistic motion and quantifiable deformation. An open-source post-processing framework was developed that corrects and inverts the XCAT-DVFs while preserving sliding motion between organs. Those post-processed DVFs are used to warp the first XCAT-generated image to consecutive time points providing a 4D phantom with a tumour that moves consistently with the anatomy, the ability to scale lung density as well as consistent and invertible DVFs. For a regularly breathing case, the inverse consistency of the DVFs was verified and the tumour motion was compared to the original XCAT. The generated phantom and DVFs were used to validate a motion-including dose reconstruction (MIDR) method using isocenter shifts to emulate rigid motion. Differences between the reconstructed doses with and without lung density scaling were evaluated. The post-processing framework produced DVFs with a maximum 95 t h -percentile inverse-consistency error of 0.02 mm. The generated phantom preserved the dominant sliding motion between the chest wall and inner organs. The tumour of the original XCAT phantom preserved its trajectory while deforming consistently with the underlying tissue. The MIDR was compared to the ground truth dose reconstruction illustrating its limitations. MIDR with and without lung density scaling resulted in small dose differences up to 1 Gy (prescription 54 Gy). The proposed open-source post-processing framework overcomes important limitations of the original XCAT phantom and makes it applicable to a wider range of validation applications within radiotherapy.

Purpose: The aim of this work was to evaluate the feasibility of cone-beam computed tomography (CBCT) and deformable image registration (DIR)–based “dose of the day” calculations for adaptive proton therapy. Methods: Intensity-modulated radiation therapy (IMRT) and proton therapy plans were designed for 3 head and neck patients that required replanning, and hence had a replan computed tomography (CT). Proton plans were generated for different beam arrangements and optimizations: intensity modulated proton therapy and single-field uniform dose. We used an in-house DIR software implemented at our institution to generate a deformed CT, by warping the planning CT onto the daily CBCT. This CBCT had a similar patient geometry to the replanned CT. Dose distributions on the replanned CT were considered the gold standard for “dose of the day” calculations, and were compared with doses on deformed CT (our method) and directly on the calibrated CBCT and rigidly aligned planning CT (alternative methods) in t...

Analysis of CT scans for studying Chronic Obstructive Pulmonary Disease (COPD) is generally limited to mean scores of disease extent. However, the evolution of local pulmonary damage may vary between patients with discordant effects on lung physiology. This limits the explanatory power of mean values in clinical studies. We present local disease and deformation distributions to address this limitation. The disease distribution aims to quantify two aspects of parenchymal damage: locally diffuse/dense disease and global homogeneity/heterogeneity. The deformation distribution links parenchymal damage to local volume change. These distributions are exploited to quantify inter-patient differences. We used manifold learning to model variations of these distributions in 743 patients from the COPDGene study. We applied manifold fusion to combine distinct aspects of COPD into a single model. We demonstrated the utility of the distributions by comparing associations between learned embeddings and measures of severity. We also illustrated the potential to identify trajectories of disease progression in a manifold space of COPD.

High precision conformal radiotherapy requires sophisticated imaging techniques to aid in target localisation for planning and treatment, particularly when organ motion due to respiration is involved. X-ray based imaging is a well-established standard for radiotherapy treatments. Over the last few years, the ability of magnetic resonance imaging (MRI) to provide radiation-free images with high-resolution and superb soft tissue contrast has highlighted the potential of this imaging modality for radiotherapy treatment planning and motion management. In addition, these advantageous properties motivated several recent developments towards combined MRI radiation therapy treatment units, enabling in-room MRI-guidance and treatment adaptation. The aim of this review is to provide an overview of the state-of-the-art in MRI-based image guidance for organ motion management in external beam radiotherapy. Methodological aspects of MRI for organ motion management are reviewed and their application in treatment planning, in-room guidance and adaptive radiotherapy described. Finally, a roadmap for an optimal use of MRI-guidance is highlighted and future challenges are discussed.

Background and purpose: The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing. Materials and methods: A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.5 x 1.5 x 5.0 mm(3)). The method employed image-derived respiratory surrogates, deformable image registration and super-resolution reconstruction. Volunteer imaging and a respiratory motion phantom were used for validation. The minimum number of dynamic acquisitions needed to calculate a representative midposition image was investigated by retrospectively subsampling the data (10-30 dynamic acquisitions). Results: Super-resolution 4D-T2w MRI (1.0 x 1.0 x 1.0 mm(3), 8 respiratory phases) did not suffer from data incompleteness and exhibited reduced stitching artefacts compared to sorted multi-slice MRI. Experiments using a respiratory motion phantom and colour-intensity projection images demonstrated a minor underestimation of the motion range. Midposition diaphragm differences in retrospectively sub-sampled acquisitions were

The ability to identify respiratory motion is crucial during radiation therapy treatment. In our study we introduced a novel data driven method based on principal component analysis (PCA) to extract a signal related to respiratory motion from cone beam CT projection data. Projection data acquired on cone beam CT devices normally has two motion component information within it, (1) respiratory induced motion and (2) detector rotational induced motion. Our novel approach for extracting a respiratory induced motion signal from projection data was based on computing PCA for different sections of the data set independently, and introducing a technique of combining the extracted signal from each section in a manner to represent the respiratory signal from the entire data set. We tested our method using simulation data set from XCAT software and a real patient data set. The respiratory signal extracted with the XCAT simulation yielded comparable result when compared to the ground truth respiratory signal. Initial results for the real patient data set are encouraging but show need for further refinements.