Dynamic Cone-beam CT Reconstruction using Spatial and Temporal Implicit Neural Representation Learning (STINR)

Objective: Dynamic cone-beam CT (CBCT) imaging is highly desired in image-guided radiation therapy to provide volumetric images with high spatial and temporal resolutions to enable applications including tumor motion tracking/prediction and intra-delivery dose calculation/accumulation. However, the dynamic CBCT reconstruction is a substantially challenging spatiotemporal inverse problem, due to the extremely limited projection sample available for each CBCT reconstruction (one projection for one CBCT volume). Approach: We developed a simultaneous spatial and temporal implicit neural representation (STINR) method for dynamic CBCT reconstruction. STINR mapped the unknown image and the evolution of its motion into spatial and temporal multi-layer perceptrons (MLPs), and iteratively optimized the neuron weighting of the MLPs via acquired projections to represent the dynamic CBCT series. In addition to the MLPs, we also introduced prior knowledge, in form of principal component analysis (PCA)-based patient-specific motion models, to reduce the complexity of the temporal INRs to address the ill-conditioned dynamic CBCT reconstruction problem. We used the extended cardiac torso (XCAT) phantom to simulate different lung motion/anatomy scenarios to evaluate STINR. The scenarios contain motion variations including motion baseline shifts, motion amplitude/frequency variations, and motion non-periodicity. The scenarios also contain inter-scan anatomical variations including tumor shrinkage and tumor position change. Main results: STINR shows consistently higher image reconstruction and motion tracking accuracy than a traditional PCA-based method and a polynomial-fitting based neural representation method. STINR tracks the lung tumor to an averaged center-of-mass error of <2 mm, with corresponding relative errors of reconstructed dynamic CBCTs <10%

A Heterogeneous Patient-Specific Biomechanical Model of the Lung for Tumor Motion Compensation and Effective Lung Radiation Therapy Planning

Radiation therapy is a main component of treatment for many lung cancer patients. However, the respiratory motion can cause inaccuracies in radiation delivery that can lead to treatment complications. In addition, the radiation-induced damage to healthy tissue limits the effectiveness of radiation treatment. Motion management methods have been developed to increase the accuracy of radiation delivery, and functional avoidance treatment planning has emerged to help reduce the chances of radiation-induced toxicity. In this work, we have developed biomechanical model-based techniques for tumor motion estimation, as well as lung functional imaging. The proposed biomechanical model accurately estimates lung and tumor motion/deformation by mimicking the physiology of respiration, while accounting for heterogeneous changes in the lung mechanics caused by COPD, a common lung cancer comorbidity. A biomechanics-based image registration algorithm is developed and is combined with an air segmentation algorithm to develop a 4DCT-based ventilation imaging technique, with potential applications in functional avoidance therapies

A biomechanical approach for real-time tracking of lung tumors during External Beam Radiation Therapy (EBRT)

Lung cancer is the most common cause of cancer related death in both men and women. Radiation therapy is widely used for lung cancer treatment. However, this method can be challenging due to respiratory motion. Motion modeling is a popular method for respiratory motion compensation, while biomechanics-based motion models are believed to be more robust and accurate as they are based on the physics of motion. In this study, we aim to develop a biomechanics-based lung tumor tracking algorithm which can be used during External Beam Radiation Therapy (EBRT). An accelerated lung biomechanical model can be used during EBRT only if its boundary conditions (BCs) are defined in a way that they can be updated in real-time. As such, we have developed a lung finite element (FE) model in conjunction with a Neural Networks (NNs) based method for predicting the BCs of the lung model from chest surface motion data. To develop the lung FE model for tumor motion prediction, thoracic 4D CT images of lung cancer patients were processed to capture the lung and diaphragm geometry, trans-pulmonary pressure, and diaphragm motion. Next, the chest surface motion was obtained through tracking the motion of the ribcage in 4D CT images. This was performed to simulate surface motion data that can be acquired using optical tracking systems. Finally, two feedforward NNs were developed, one for estimating the trans-pulmonary pressure and another for estimating the diaphragm motion from chest surface motion data. The algorithm development consists of four steps of: 1) Automatic segmentation of the lungs and diaphragm, 2) diaphragm motion modelling using Principal Component Analysis (PCA), 3) Developing the lung FE model, and 4) Using two NNs to estimate the trans-pulmonary pressure values and diaphragm motion from chest surface motion data. The results indicate that the Dice similarity coefficient between actual and simulated tumor volumes ranges from 0.76±0.04 to 0.91±0.01, which is favorable. As such, real-time lung tumor tracking during EBRT using the proposed algorithm is feasible. Hence, further clinical studies involving lung cancer patients to assess the algorithm performance are justified

Investigation of time-resolved volumetric MRI to enhance MR-guided radiotherapy of moving lung tumors

In photon radiotherapy of lung cancer, respiratory-induced motion introduces systematic and statistical uncertainties in treatment planning and dose delivery. By integrating magnetic resonance imaging (MRI) in the treatment planning process in MR-guided radiotherapy (MRgRT), uncertainties in target volume definition can be reduced with respect to state-of-the-art X-ray-based approaches. Furthermore, MR-guided linear accelerators (MR-Linacs) offer dose delivery with enhanced accuracy and precision through daily treatment plan adaptation and gated beam delivery based on real-time MRI. Today, the potential of MRgRT of moving targets is, however, not fully exploited due to the lack of time-resolved four-dimensional MRI (4D-MRI) in clinical practice. Therefore, the aim of this thesis was to develop and experimentally validate new methods for motion characterization and estimation with 4D-MRI for MRgRT of lung cancer. Different concepts were investigated for all phases of the clinical workflow - treatment planning, beam delivery, and post-treatment analysis. Firstly, a novel internal target volume (ITV) definition method based on the probability-of-presence of moving tumors derived from real-time 4D-MRI was developed. The ability of the ITVs to prospectively account for changes occurring over the course of several weeks was assessed in retrospective geometric analyses of lung cancer patient data. Higher robustness of the probabilistic 4D-MRI-based ITVs against interfractional changes was observed compared to conventional target volumes defined with four-dimensional computed tomography (4D-CT). The study demonstrated that motion characterization over extended times enabled by real-time 4D-MRI can reduce systematic and statistical uncertainties associated with today’s standard workflow. Secondly, experimental validation of a published motion estimation method - the propagation method - was conducted with a porcine lung phantom under realistic patient-like conditions. Estimated 4D-MRIs with a temporal resolution of 3.65 Hz were created based on orthogonal 2D cine MRI acquired at the scanner unit of an MR-Linac. A comparison of these datasets with ground truth respiratory-correlated 4D-MRIs in geometric analyses showed that the propagation method can generate geometrically accurate estimated 4D-MRIs. These could decrease target localization errors and enable 3D motion monitoring during beam delivery at the MR-Linac in the future. Lastly, the propagation method was extended to create continuous time-resolved estimated synthetic CTs (tresCTs). The proposed method was experimentally tested with the porcine lung phantom, successively imaged at a CT scanner and an MR-Linac. A high agreement of the images and corresponding dose distributions of the tresCTs and measured ground truth 4D-CTs was found in geometric and dosimetric analyses. The tresCTs could be used for post-treatment time-resolved reconstruction of the delivered dose to guide treatment adaptations in the future. These studies represent important steps towards a clinical application of time-resolved 4D-MRI methods for enhanced MRgRT of lung tumors in the near future

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society

Modeling and Simulation in Engineering

This book provides an open platform to establish and share knowledge developed by scholars, scientists, and engineers from all over the world, about various applications of the modeling and simulation in the design process of products, in various engineering fields. The book consists of 12 chapters arranged in two sections (3D Modeling and Virtual Prototyping), reflecting the multidimensionality of applications related to modeling and simulation. Some of the most recent modeling and simulation techniques, as well as some of the most accurate and sophisticated software in treating complex systems, are applied. All the original contributions in this book are jointed by the basic principle of a successful modeling and simulation process: as complex as necessary, and as simple as possible. The idea is to manipulate the simplifying assumptions in a way that reduces the complexity of the model (in order to make a real-time simulation), but without altering the precision of the results

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