Consistent and invertible deformation vector fields for a breathing anthropomorphic phantom: a post-processing framework for the XCAT phantom.

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 [Formula: see text]-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

3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

GIFTed Demons: deformable image registration with local structure-preserving regularization using supervoxels for liver applications.

Deformable image registration, a key component of motion correction in medical imaging, needs to be efficient and provides plausible spatial transformations that reliably approximate biological aspects of complex human organ motion. Standard approaches, such as Demons registration, mostly use Gaussian regularization for organ motion, which, though computationally efficient, rule out their application to intrinsically more complex organ motions, such as sliding interfaces. We propose regularization of motion based on supervoxels, which provides an integrated discontinuity preserving prior for motions, such as sliding. More precisely, we replace Gaussian smoothing by fast, structure-preserving, guided filtering to provide efficient, locally adaptive regularization of the estimated displacement field. We illustrate the approach by applying it to estimate sliding motions at lung and liver interfaces on challenging four-dimensional computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging datasets. The results show that guided filter-based regularization improves the accuracy of lung and liver motion correction as compared to Gaussian smoothing. Furthermore, our framework achieves state-of-the-art results on a publicly available CT liver dataset

Improving the Accuracy of CT-derived Attenuation Correction in Respiratory-Gated PET/CT Imaging

The effect of respiratory motion on attenuation correction in Fludeoxyglucose (18F) positron emission tomography (FDG-PET) was investigated. Improvements to the accuracy of computed tomography (CT) derived attenuation correction were obtained through the alignment of the attenuation map to each emission image in a respiratory gated PET scan. Attenuation misalignment leads to artefacts in the reconstructed PET image and several methods were devised for evaluating the attenuation inaccuracies caused by this. These methods of evaluation were extended to finding the frame in the respiratory gated PET which best matched the CT. This frame was then used as a reference frame in mono-modality compensation for misalignment. Attenuation correction was found to affect the quantification of tumour volumes; thus a regional analysis was used to evaluate the impact of mismatch and the benefits of compensating for misalignment. Deformable image registration was used to compensate for misalignment, however, there were inaccuracies caused by the poor signal-to-noise ratio (SNR) in PET images. Two models were developed that were robust to a poor SNR allowing for the estimation of deformation from very noisy images. Firstly, a cross population model was developed by statistically analysing the respiratory motion in 10 4DCT scans. Secondly, a 1D model of respiration was developed based on the physiological function of respiration. The 1D approach correctly modelled the expansion and contraction of the lungs and the differences in the compressibility of lungs and surrounding tissues. Several additional models were considered but were ruled out based on their poor goodness of fit to 4DCT scans. Approaches to evaluating the developed models were also used to assist with optimising for the most accurate attenuation correction. It was found that the multimodality registration of the CT image to the PET image was the most accurate approach to compensating for attenuation correction mismatch. Mono-modality image registration was found to be the least accurate approach, however, incorporating a motion model improved the accuracy of image registration. The significance of these findings is twofold. Firstly, it was found that motion models are required to improve the accuracy in compensating for attenuation correction mismatch and secondly, a validation method was found for comparing approaches to compensating for attenuation mismatch

Improving the Accuracy of CT-derived Attenuation Correction in Respiratory-Gated PET/CT Imaging

The effect of respiratory motion on attenuation correction in Fludeoxyglucose (18F) positron emission tomography (FDG-PET) was investigated. Improvements to the accuracy of computed tomography (CT) derived attenuation correction were obtained through the alignment of the attenuation map to each emission image in a respiratory gated PET scan. Attenuation misalignment leads to artefacts in the reconstructed PET image and several methods were devised for evaluating the attenuation inaccuracies caused by this. These methods of evaluation were extended to finding the frame in the respiratory gated PET which best matched the CT. This frame was then used as a reference frame in mono-modality compensation for misalignment. Attenuation correction was found to affect the quantification of tumour volumes; thus a regional analysis was used to evaluate the impact of mismatch and the benefits of compensating for misalignment. Deformable image registration was used to compensate for misalignment, however, there were inaccuracies caused by the poor signal-to-noise ratio (SNR) in PET images. Two models were developed that were robust to a poor SNR allowing for the estimation of deformation from very noisy images. Firstly, a cross population model was developed by statistically analysing the respiratory motion in 10 4DCT scans. Secondly, a 1D model of respiration was developed based on the physiological function of respiration. The 1D approach correctly modelled the expansion and contraction of the lungs and the differences in the compressibility of lungs and surrounding tissues. Several additional models were considered but were ruled out based on their poor goodness of fit to 4DCT scans. Approaches to evaluating the developed models were also used to assist with optimising for the most accurate attenuation correction. It was found that the multimodality registration of the CT image to the PET image was the most accurate approach to compensating for attenuation correction mismatch. Mono-modality image registration was found to be the least accurate approach, however, incorporating a motion model improved the accuracy of image registration. The significance of these findings is twofold. Firstly, it was found that motion models are required to improve the accuracy in compensating for attenuation correction mismatch and secondly, a validation method was found for comparing approaches to compensating for attenuation mismatch

Deep learning in medical image registration: introduction and survey

Image registration (IR) is a process that deforms images to align them with respect to a reference space, making it easier for medical practitioners to examine various medical images in a standardized reference frame, such as having the same rotation and scale. This document introduces image registration using a simple numeric example. It provides a definition of image registration along with a space-oriented symbolic representation. This review covers various aspects of image transformations, including affine, deformable, invertible, and bidirectional transformations, as well as medical image registration algorithms such as Voxelmorph, Demons, SyN, Iterative Closest Point, and SynthMorph. It also explores atlas-based registration and multistage image registration techniques, including coarse-fine and pyramid approaches. Furthermore, this survey paper discusses medical image registration taxonomies, datasets, evaluation measures, such as correlation-based metrics, segmentation-based metrics, processing time, and model size. It also explores applications in image-guided surgery, motion tracking, and tumor diagnosis. Finally, the document addresses future research directions, including the further development of transformers

Doctor of Philosophy

dissertationX-ray computed tomography (CT) is a widely popular medical imaging technique that allows for viewing of in vivo anatomy and physiology. In order to produce high-quality images and provide reliable treatment, CT imaging requires the precise knowledge of t

Articulated patient model in high-precision radiation therapy

In modern high precision radiotherapy, changes in the anatomy of the patient over the course of treatment pose a major challenge. An accurate assessment of occurring anatomical variations is the key requirement to enable an adaptation of the treatment plan for ensuring a highly precise treatment. Comparison of commonly used deformable image registration shows large discrepancies regarding the quality of anatomical alignment, benchmarked on a common data pool. One of the main reasons is found in widely used transformation models, insufficiently reflecting the actual deformation behaviour of the underlying tissue. Thus, especially in the highly heterogeneous head and neck area, which is characterized by many organs at risk being in proximity to the tumor as well as posture changes induced by the interplay of several bones, an accurate assessment of anatomical changes is essential for a successful adaptive radiotherapy. A physically meaningful transformation model offering a high biofidelity is required to provide an accurate anatomical alignment in such area. In this work, a novel biomechanical deformation model based on kinematics and multi-body physics for the whole head and neck area is introduced to guarantee the representation of physically meaningful transformations. The developed kinematic model is individually tailored to each patient as it is based on the delineated bones extracted from the computer tomography scan. It encompasses all bones relevant for head and neck cancer treatment, including bones of the proximal upper extremities, the shoulder girdle, cranial region, the rib cage and the vertebral column. Moreover, the model is designed to be easily extendible to other body regions. All bones are connected by ball and socket joints, which are automatically localized based on their individual geometries. A kinematic graph maintains the hierarchy of the connected bones across the whole skeleton to enable the propagation of local transformations to other body regions by inverse kinematics. Accuracy, robustness and computational efficiency of the kinematic model were retrospectively evaluated on patient datasets representative for typical inter-fractional variations as well as separately acquired image scans with large arms-up to arms-down posture changes. Using landmarks defined by multiple observers as reference, the overall mean accuracy of the kinematic model in reproducing postures in the image scans was found to be around 1 millimetre, which is settled slightly above the inter-observer variation. In detail, the assessed accuracy revealed potential for improvement regarding the automated positioning of the intervertebral joints in the region of the cervical spine. Due to the complex shape of the vertebrae, a relocation of the joint rotation centres towards the line connecting the centres of the intervertebral disks seems beneficial. Moreover, the use of ball and socket joints for the acromioclavicular joints has shown to be insufficient for mimicking the large arms-up to arms-down posture change due to the lack of representing translational offsets, observed in the image scans. The strong regularization of the permissible deformations in the skeletal anatomy leads to a higher robustness against conflicting input such as flawed or mixed-up anatomical feature points. Furthermore, such a physical-object-oriented transformation model requires even less input to describe meaningful deformations. With the total degrees of freedom of the kinematic head and neck model limited to those specified by the joints, the computation of new arbitrary skeletal postures is achieved within less than 50 milliseconds. With such efficient computation on the one hand and the strong regularization of deformations on the other hand, the kinematic model seems suitable for its application in a registration approach. In addition, it was demonstrated how the kinematic model can be successfully embedded into a registration approach as a transformation model to enable the fully automatic extraction of anatomical variations from image scans. This was accomplished by coupling the model to an extended simplex downhill optimizer and an overlap based similarity metric. The anatomy of pre-selected bones is aligned following a hierarchical optimization scheme. In conclusion, the novel developed kinematic model guarantees a deformation modelling of high biofidelity and efficiency, thus promising an assessment of anatomical changes without the need of an extensive visual inspection of the results as otherwise expected. To date, successful application of adaptive radiotherapy especially for tumors in regions characterized by a high anatomical flexibility is hampered by a lacking reliability of conventional deformation models. While associated uncertainties can be compensated at the cost of extended safety margins for photon therapy, prevailing range uncertainties when using particles currently impede the treatment of tumors in such areas. The dissemination of the proposed kinematic deformation model into the clinics provides a way to lay the foundation towards broadening the spectrum of patients eligible for treatment with particles, carried out at the increasing number of particle therapy centres worldwide