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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.

Purpose: In addition to patient set-up uncertainties, anatomical deformations, e.g., weight loss, lead to time-dependent differences between the planned and delivered dose in a radiotherapy course that currently cannot easily be predicted. The aim of this study was to create time-varying prediction models to describe both the average and residual anatomical deformations. Methods: Weekly population-based principal component analysis models were generated from on-treatment cone-beam CT scans (CBCTs) of 30 head and neck cancer patients, with additional data of 35 patients used as a validation cohort. We simulated treatment courses accounting for a) anatomical deformations, b) set-up uncertainties and c) a combination of both. The dosimetric effects of the simulated deformations were compared to a direct dose accumulation based on deformable registration of the CBCT data. Results: Set-up uncertainties were seen to have a larger effect on the organ at risk (OAR) doses than anatomical deformations for all OARs except the larynx and the primary CTV. Distributions from simulation results were in good agreement with those of the accumulated dose. Conclusions: We present a novel method of modelling time-varying organ deformations in head and neck cancer. The effect on the OAR doses from these deformations are smaller than the effect of set-up uncertainties for most OARs. These models can, for instance, be used to predict which patients could benefit from adaptive radiotherapy, prior to commencing treatment.

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.

Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to ‘see what we treat, as we treat’ and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT.

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.

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.

Accurate registration of images depicting respiratory motion, e.g. 4DCT or 4DMR, can be challenging due to sliding motion that occurs between the chest wall and organs within the pleural sac (lungs, mediastinum, liver). In this paper we propose a methodology that (1) segments one of the images to be registered (the source or floating/moving image) into two distinct regions by fitting a statistical motion mask, and (2) registers the image with a modified B-spline registration algorithm that can account for sliding motion between the regions. This registration requires the segmentation of the regions in the source image domain as a signed distance map. Two underlying transformations allow the regions to deform independently, while a constraint term based on the transformed distance maps penalises gaps and overlaps between the regions. Although implemented in a B-spline algorithm, the required modifications are not specific to the transformation type and thus can be applied to parametric and non-parametric frameworks alike. The registration accuracy is evaluated using the landmark registration error on the basis of the publicly available DIR-Lab dataset. The overall average landmark error after registration is 1.21 mm and the average gap and overlap volumes are 26.4 cm\(^3\) and 34.5 cm\(^3\) respectively. The fitted statistical motion masks are compared to previously proposed motion masks and the corresponding mean Dice coefficient is 0.96.

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm.

Purpose: To compare two methods of automatic breast segmentation with each other and with manual segmentation in a large subject cohort. To discuss the factors involved in selecting the most appropriate algorithm for automatic segmentation and, in particular, to investigate the appropriateness of overlap measures (e.g., Dice and Jaccard coefficients) as the primary determinant in algorithm selection. Methods: Two methods of breast segmentation were applied to the task of calculating MRI breast density in 200 subjects drawn from the Avon Longitudinal Study of Parents and Children, a large cohort study with an MRI component. A semiautomated, bias-corrected, fuzzy C-means (BC-FCM) method was combined with morphological operations to segment the overall breast volume from in-phase Dixon images. The method makes use of novel, problem-specific insights. The resulting segmentation mask was then applied to the corresponding Dixon water and fat images, which were combined to give Dixon MRI density values. Contemporaneously acquired T-1- and T-2-weighted image datasets were analyzed using a novel and fully automated algorithm involving image filtering, landmark identification, and explicit location of the pectoral muscle boundary. Within the region found, fat-water discrimination was performed using an Expectation Maximization-Markov Random Field technique, yielding a second independent estimate of MRI density. Results: Images are presented for two individual women, demonstrating how the difficulty of the problem is highly subject-specific. Dice and Jaccard coefficients comparing the semiautomated BC-FCM method, operating on Dixon source data, with expert manual segmentation are presented. The corresponding results for the method based on T-1- and T-2-weighted data are slightly lower in the individual cases shown, but scatter plots and interclass correlations for the cohort as a whole show that both methods do an excellent job in segmenting and classifying breast tissue. Conclusions: Epidemiological results demonstrate that both methods of automated segmentation are suitable for the chosen application and that it is important to consider a range of factors when choosing a segmentation algorithm, rather than focus narrowly on a single metric such as the Dice coefficient. (C) 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Biomechanical modelling enables large deformation simulations of breast tissues under different loading conditions to be performed. Such simulations can be utilised to transform prone Magnetic Resonance (MR) images into a different patient position, such as upright or supine. We present a novel integration of biomechanical modelling with a surface registration algorithm which optimises the unknown material parameters of a biomechanical model and performs a subsequent regularised surface alignment. This allows deformations induced by effects other than gravity, such as those due to contact of the breast and MR coil, to be reversed. Correction displacements are applied to the biomechanical model enabling transformation of the original pre-surgical images to the corresponding target position. The algorithm is evaluated for the prone-to-supine case using prone MR images and the skin outline of supine Computed Tomography (CT) scans for three patients. A mean target registration error (TRE) of 10:9 mm for internal structures is achieved. For the prone-to-upright scenario, an optical 3D surface scan of one patient is used as a registration target and the nipple distances after alignment between the transformed MRI and the surface are 10:1 mm and 6:3 mm respectively.

Breast radiology encompasses the full range of imaging modalities from routine imaging via x-ray mammography, magnetic resonance imaging and ultrasound (both two- and three-dimensional), to more recent technologies such as digital breast tomosynthesis, and dedicated breast imaging systems for positron emission mammography and ultrasound tomography. In addition new and experimental modalities, such as Photoacoustics, Near Infrared Spectroscopy and Electrical Impedance Tomography etc, are emerging. The breast is a highly deformable structure however, and this greatly complicates visual comparison of imaging modalities for the purposes of breast screening, cancer diagnosis (including image guided biopsy), tumour staging, treatment monitoring, surgical planning and simulation of the effects of surgery and wound healing etc. Due primarily to the challenges posed by these gross, non-rigid deformations, development of automated methods which enable registration, and hence fusion, of information within and across breast imaging modalities, and between the images and the physical space of the breast during interventions, remains an active research field which has yet to translate suitable methods into clinical practice. This review describes current research in the field of breast biomechanical modelling and identifies relevant publications where the resulting models have been incorporated into breast image registration and simulation algorithms. Despite these developments there remain a number of issues that limit clinical application of biomechanical modelling. These include the accuracy of constitutive modelling, implementation of representative boundary conditions, failure to meet clinically acceptable levels of computational cost, challenges associated with automating patient-specific model generation (i.e. robust image segmentation and mesh generation) and the complexity of applying biomechanical modelling methods in routine clinical practice.

Patient-specific surgical predictions of Breast Conserving Therapy, through mechano-biological simulations, could inform the shared decision making process between clinicians and patients by enabling the impact of different surgical options to be visualised. We present an overview of our processing workflow that integrates MR images and three dimensional optical surface scans into a personalised model. Utilising an interactively generated surgical plan, a multi-scale open source finite element solver is employed to simulate breast deformity based on interrelated physiological and biomechanical processes that occur post surgery. Our outcome predictions, based on the pre-surgical imaging, were validated by comparing the simulated outcome with follow-up surface scans of four patients acquired 6 to 12 months post-surgery. A mean absolute surface distance of 3.3i¾?mm between the follow-up scan and the simulation was obtained.

There is currently an increasing interest in combining the information obtained from radiology and histology with the intent of gaining a better understanding of how different tumour morphologies can lead to distinctive radiological signs which might predict overall treatment outcome. Relating information at different resolution scales is challenging. Reconstructing 3D volumes from histology images could be the key to interpreting and relating the radiological image signal to tissue microstructure. The goal of this study is to determine the minimum sampling (maximum spacing between histological sections through a fixed surgical specimen) required to create a 3D reconstruction of the specimen to a specific tolerance. We present initial results for one lumpectomy specimen case where 33 consecutive histology slides were acquired.

Determining corresponding regions between an MRI and an X-ray mammogram is a clinically useful task that is challenging for radiologists due to the large deformation that the breast undergoes between the two image acquisitions. In this work we propose an intensity-based image registration framework, where the biomechanical transformation model parameters and the rigid-body transformation parameters are optimised simultaneously. Patient-specific biomechanical modelling of the breast derived from diagnostic, prone MRI has been previously used for this task. However, the high computational time associated with breast compression simulation using commercial packages, did not allow the optimisation of both pose and FEM parameters in the same framework. We use a fast explicit Finite Element (FE) solver that runs on a graphics card, enabling the FEM-based transformation model to be fully integrated into the optimisation scheme. The transformation model has seven degrees of freedom, which include parameters for both the initial rigid-body pose of the breast prior to mammographic compression, and those of the biomechanical model. The framework was tested on ten clinical cases and the results were compared against an affine transformation model, previously proposed for the same task. The mean registration error was 11:6 � 3:8 mm for the CC and 11 � 5:4 mm for the MLO view registrations, indicating that this could be a useful clinical tool. 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://

The female breast undergoes large scale deformations, when the patient position is changed from the prone position where imaging is usually performed to the supine position, which is the standard surgical setting. To guide the surgical procedure, MRI data need to be aligned between these two positions. Image registration techniques which are purely intensity based usually fail, when prone and supine image data are to be aligned. To address this we use patient specific biomechanical models to provide an initial deformation of the breast prior to registration. In contrast to previous methods, we use these models to estimate the zero-gravity reference state for both the prone and supine configurations and perform the subsequent registration in this space. In this symmetric approach we incorporate non-linear material models and displacement boundary conditions on the chest wall which lead to clinically useful accuracy in the simulation and subsequent registration.

Frontiers in neuroinformatics 5, 34 (2011). doi:10.3389/fninf.2011.00034, Published by Frontiers Research Foundation, Lausanne

In dieser Arbeit wird die Segmentierung von Gehirngewebe aus Kopfaufnahmen von Ratten mittels Level-Set-Methoden vorgeschlagen. Dazu wird ein zweidimensionaler, kontrastbasierter Ansatz zu einem dreidimensionalen, lokal an die Bildintensitat adaptierten Segmentierer erweitert. Es wird gezeigt, dass mit diesem echten 3D-Ansatz die lokalen Bildstrukturen besser berucksichtigt werden konnen. Insbesondere Magnet-Resonanz-Tomographien (MRTs) mit globalen Helligkeitsgradienten, beispielsweise bedingt durch Oberfiachenspulen, konnen auf diese Weise zuverlassiger und ohne weitere Vorverarbeitungsschritte segmentiert werden. Die Leistungsfahigkeit des Algorithmus wird experimentell an Hand dreier Rattenhirn-MRTs demonstriert.