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

Coronary Artery Segmentation and Motion Modelling

Conventional coronary artery bypass surgery requires invasive sternotomy and the use of a cardiopulmonary bypass, which leads to long recovery period and has high infectious potential. Totally endoscopic coronary artery bypass (TECAB) surgery based on image guided robotic surgical approaches have been developed to allow the clinicians to conduct the bypass surgery off-pump with only three pin holes incisions in the chest cavity, through which two robotic arms and one stereo endoscopic camera are inserted. However, the restricted field of view of the stereo endoscopic images leads to possible vessel misidentification and coronary artery mis-localization. This results in 20-30% conversion rates from TECAB surgery to the conventional approach. We have constructed patient-specific 3D + time coronary artery and left ventricle motion models from preoperative 4D Computed Tomography Angiography (CTA) scans. Through temporally and spatially aligning this model with the intraoperative endoscopic views of the patient's beating heart, this work assists the surgeon to identify and locate the correct coronaries during the TECAB precedures. Thus this work has the prospect of reducing the conversion rate from TECAB to conventional coronary bypass procedures. This thesis mainly focus on designing segmentation and motion tracking methods of the coronary arteries in order to build pre-operative patient-specific motion models. Various vessel centreline extraction and lumen segmentation algorithms are presented, including intensity based approaches, geometric model matching method and morphology-based method. A probabilistic atlas of the coronary arteries is formed from a group of subjects to facilitate the vascular segmentation and registration procedures. Non-rigid registration framework based on a free-form deformation model and multi-level multi-channel large deformation diffeomorphic metric mapping are proposed to track the coronary motion. The methods are applied to 4D CTA images acquired from various groups of patients and quantitatively evaluated

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Dynamic Image Processing for Guidance of Off-pump Beating Heart Mitral Valve Repair

Compared to conventional open heart procedures, minimally invasive off-pump beating heart mitral valve repair aims to deliver equivalent treatment for mitral regurgitation with reduced trauma and side effects. However, minimally invasive approaches are often limited by the lack of a direct view to surgical targets and/or tools, a challenge that is compounded by potential movement of the target during the cardiac cycle. For this reason, sophisticated image guidance systems are required in achieving procedural efficiency and therapeutic success. The development of such guidance systems is associated with many challenges. For example, the system should be able to provide high quality visualization of both cardiac anatomy and motion, as well as augmenting it with virtual models of tracked tools and targets. It should have the capability of integrating pre-operative images to the intra-operative scenario through registration techniques. The computation speed must be sufficiently fast to capture the rapid cardiac motion. Meanwhile, the system should be cost effective and easily integrated into standard clinical workflow. This thesis develops image processing techniques to address these challenges, aiming to achieve a safe and efficient guidance system for off-pump beating heart mitral valve repair. These techniques can be divided into two categories, using 3D and 2D image data respectively. When 3D images are accessible, a rapid multi-modal registration approach is proposed to link the pre-operative CT images to the intra-operative ultrasound images. The ultrasound images are used to display the real time cardiac motion, enhanced by CT data serving as high quality 3D context with annotated features. I also developed a method to generate synthetic dynamic CT images, aiming to replace real dynamic CT data in such a guidance system to reduce the radiation dose applied to the patients. When only 2D images are available, an approach is developed to track the feature of interest, i.e. the mitral annulus, based on bi-plane ultrasound images and a magnetic tracking system. The concept of modern GPU-based parallel computing is employed in most of these approaches to accelerate the computation in order to capture the rapid cardiac motion with desired accuracy. Validation experiments were performed on phantom, animal and human data. The overall accuracy of registration and feature tracking with respect to the mitral annulus was about 2-3mm with computation time of 60-400ms per frame, sufficient for one update per cardiac cycle. It was also demonstrated in the results that the synthetic CT images can provide very similar anatomical representations and registration accuracy compared to that of the real dynamic CT images. These results suggest that the approaches developed in the thesis have good potential for a safer and more effective guidance system for off-pump beating heart mitral valve repair

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

Evaluation of deformable image registration for improved 4D CT-derived ventilation for image guided radiotherapy

Recent treatment planning studies have demonstrated the use of physiologic images in radiation therapy treatment planning to identify regions for functional avoidance. This image-guided radiotherapy (IGRT) strategy may reduce the injury and/or functional loss following thoracic radiotherapy. 4D computed tomography (CT), developed for radiotherapy treatment planning, is a relatively new imaging technique that allows the acquisition of a time-varying sequence of 3D CT images of the patient\u27s lungs through the respiratory cycle. Guerrero et al. developed a method to calculate ventilation imaging from 4D CT, which is potentially better suited and more broadly available for IGRT than the current standard imaging methods. The key to extracting function information from 4D CT is the construction of a volumetric deformation field that accurately tracks the motion of the patient\u27s lungs during the respiratory cycle. The spatial accuracy of the displacement field directly impacts the ventilation images; higher spatial registration accuracy will result in less ventilation image artifacts and physiologic inaccuracies. Presently, a consistent methodology for spatial accuracy evaluation of the DIR transformation is lacking. Evaluation of the 4D CT-derived ventilation images will be performed to assess correlation with global measurements of lung ventilation, as well as regional correlation of the distribution of ventilation with the current clinical standard SPECT. This requires a novel framework for both the detailed assessment of an image registration algorithm\u27s performance characteristics as well as quality assurance for spatial accuracy assessment in routine application. Finally, we hypothesize that hypo-ventilated regions, identified on 4D CT ventilation images, will correlate with hypo-perfused regions in lung cancer patients who have obstructive lesions. A prospective imaging trial of patients with locally advanced non-small-cell lung cancer will allow this hypothesis to be tested. These advances are intended to contribute to the validation and clinical implementation of CT-based ventilation imaging in prospective clinical trials, in which the impact of this imaging method on patient outcomes may be tested

Regression learning for 2D/3D image registration

Image registration is a common technique in medical image analysis. The goal of image registration is to discover the underlying geometric transformation of target objects or regions appearing in two images. This dissertation investigates image registration methods for lung Image-Guided Radiation Therapy (IGRT). The goal of lung IGRT is to lay the radiation beam on the ever-changing tumor centroid but avoid organs at risk under the patient's continuous respiratory motion during the therapeutic procedure. To achieve this goal, I developed regression learning methods that compute the patient's 3D deformation between a treatment-time acquired x-ray image and a treatment-planning CT image (2D/3D image registration) in real-time. The real-time computation involves learning x-ray to 3D deformation regressions from a simulated patient-specific training set that captures credible deformation variations obtained from the patient's Respiratory-Correlated CT (RCCT) images. At treatment time, the learned regressions can be applied efficiently to the acquired x-ray image to yield an estimation of the patient's 3D deformation. In this dissertation, three regression learning methods - linear, non-linear, and locally-linear regression learning methods are presented to approach this 2D/3D image registration problem.Doctor of Philosoph

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