Statistical Shape Modelling and Segmentation of the Respiratory Airway

The human respiratory airway consists of the upper (nasal cavity, pharynx) and the lower (trachea, bronchi) respiratory tracts. Accurate segmentation of these two airway tracts can lead to better diagnosis and interpretation of airway-specific diseases, and lead to improvement in the localization of abnormal metabolic or pathological sites found within and/or surrounding the respiratory regions. Due to the complexity and the variability displayed in the anatomical structure of the upper respiratory airway along with the challenges in distinguishing the nasal cavity from non-respiratory regions such as the paranasal sinuses, it is difficult for existing algorithms to accurately segment the upper airway without manual intervention. This thesis presents an implicit non-parametric framework for constructing a statistical shape model (SSM) of the upper and lower respiratory tract, capable of distinct shape generation and be adapted for segmentation. An SSM of the nasal cavity was successfully constructed using 50 nasal CT scans. The performance of the SSM was evaluated for compactness, specificity and generality. An averaged distance error of 1.47 mm was measured for the generality assessment. The constructed SSM was further adapted with a modified locally constrained random walk algorithm to segment the nasal cavity. The proposed algorithm was evaluated on 30 CT images and outperformed comparative state-of-the-art and conventional algorithms. For the lower airway, a separate algorithm was proposed to automatically segment the trachea and bronchi, and was designed to tolerate the image characteristics inherent in low-contrast CT images. The algorithm was evaluated on 20 clinical low-contrast CT from PET-CT patient studies and demonstrated better performance (87.1±2.8 DSC and distance error of 0.37±0.08 mm) in segmentation results against comparative state-of-the-art algorithms

Quantitative Evaluation of Pulmonary Emphysema Using Magnetic Resonance Imaging and x-ray Computed Tomography

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality affecting at least 600 million people worldwide. The most widely used clinical measurements of lung function such as spirometry and plethysmography are generally accepted for diagnosis and monitoring of the disease. However, these tests provide only global measures of lung function and they are insensitive to early disease changes. Imaging tools that are currently available have the potential to provide regional information about lung structure and function but at present are mainly used for qualitative assessment of disease and disease progression. In this thesis, we focused on the application of quantitative measurements of lung structure derived from 1H magnetic resonance imaging (MRI) and high resolution computed tomography (CT) in subjects diagnosed with COPD by a physician. Our results showed that significant and moderately strong relationship exists between 1H signal intensity (SI) and 3He apparent diffusion coefficient (ADC), as well as between 1H SI and CT measurements of emphysema. This suggests that these imaging methods may be quantifying the same tissue changes in COPD, and that pulmonary 1H SI may be used effectively to monitor emphysema as a complement to CT and noble gas MRI. Additionally, our results showed that objective multi-threshold analysis of CT images for emphysema scoring that takes into account the frequency distribution of each Hounsfield unit (HU) threshold was effective in correctly classifying the patient into COPD and healthy subgroups. Finally, we found a significant correlation between whole lung average subjective and objective emphysema scores with high inter-observer agreement. It is concluded that 1H MRI and high resolution CT can be used to quantitatively evaluate lung tissue alterations in COPD subjects

Synergistic Visualization And Quantitative Analysis Of Volumetric Medical Images

The medical diagnosis process starts with an interview with the patient, and continues with the physical exam. In practice, the medical professional may require additional screenings to precisely diagnose. Medical imaging is one of the most frequently used non-invasive screening methods to acquire insight of human body. Medical imaging is not only essential for accurate diagnosis, but also it can enable early prevention. Medical data visualization refers to projecting the medical data into a human understandable format at mediums such as 2D or head-mounted displays without causing any interpretation which may lead to clinical intervention. In contrast to the medical visualization, quantification refers to extracting the information in the medical scan to enable the clinicians to make fast and accurate decisions. Despite the extraordinary process both in medical visualization and quantitative radiology, efforts to improve these two complementary fields are often performed independently and synergistic combination is under-studied. Existing image-based software platforms mostly fail to be used in routine clinics due to lack of a unified strategy that guides clinicians both visually and quan- titatively. Hence, there is an urgent need for a bridge connecting the medical visualization and automatic quantification algorithms in the same software platform. In this thesis, we aim to fill this research gap by visualizing medical images interactively from anywhere, and performing a fast, accurate and fully-automatic quantification of the medical imaging data. To end this, we propose several innovative and novel methods. Specifically, we solve the following sub-problems of the ul- timate goal: (1) direct web-based out-of-core volume rendering, (2) robust, accurate, and efficient learning based algorithms to segment highly pathological medical data, (3) automatic landmark- ing for aiding diagnosis and surgical planning and (4) novel artificial intelligence algorithms to determine the sufficient and necessary data to derive large-scale problems

Deep Learning-based Radiomics Framework for Multi-Modality PET-CT Images

Multimodal positron emission tomography - computed tomography (PET-CT) imaging is widely regarded as the imaging modality of choice for cancer management. This is because PET-CT combines the high sensitivity of PET in detecting regions of abnormal functions and the specificity of CT in depicting the underlying anatomy of where the abnormal functions are occurring. Radiomics is an emerging research field that enables the extraction and analysis of quantitative features from medical images, providing valuable insights into the underlying pathophysiology that cannot be discerned by the naked eyes. This information is capable of assisting decision-making in clinical practice, leading to better personalised treatment planning, patient outcome prediction, and therapy response assessment. The aim of this thesis is to propose a new deep learning-based radiomics framework for multimodal PET-CT images. The proposed framework comprises of three methods: 1) a tumour segmentation method via a self-supervision enabled false positive and false negative reduction network; 2) a constrained hierarchical multi-modality feature learning is constructed to predict the patient outcome with multimodal PET-CT images; 3) an automatic neural architecture search method to automatically find the optimal network architecture for both patient outcome prediction and tumour segmentation. Extensive experiments have been conducted on three datasets, including one public soft-tissue sarcomas dataset, one public challenge dataset, and one in-house lung cancer data. The results demonstrated that the proposed methods obtained better performance in all tasks when compared to the state-of-the-art methods

Segmentation, tracking, and kinematics of lung parenchyma and lung tumors from 4D CT with application to radiation treatment planning.

This thesis is concerned with development of techniques for efficient computerized analysis of 4-D CT data. The goal is to have a highly automated approach to segmentation of the lung boundary and lung nodules inside the lung. The determination of exact lung tumor location over space and time by image segmentation is an essential step to track thoracic malignancies. Accurate image segmentation helps clinical experts examine the anatomy and structure and determine the disease progress. Since 4-D CT provides structural and anatomical information during tidal breathing, we use the same data to also measure mechanical properties related to deformation of the lung tissue including Jacobian and strain at high resolutions and as a function of time. Radiation Treatment of patients with lung cancer can benefit from knowledge of these measures of regional ventilation. Graph-cuts techniques have been popular for image segmentation since they are able to treat highly textured data via robust global optimization, avoiding local minima in graph based optimization. The graph-cuts methods have been used to extract globally optimal boundaries from images by s/t cut, with energy function based on model-specific visual cues, and useful topological constraints. The method makes N-dimensional globally optimal segmentation possible with good computational efficiency. Even though the graph-cuts method can extract objects where there is a clear intensity difference, segmentation of organs or tumors pose a challenge. For organ segmentation, many segmentation methods using a shape prior have been proposed. However, in the case of lung tumors, the shape varies from patient to patient, and with location. In this thesis, we use a shape prior for tumors through a training step and PCA analysis based on the Active Shape Model (ASM). The method has been tested on real patient data from the Brown Cancer Center at the University of Louisville. We performed temporal B-spline deformable registration of the 4-D CT data - this yielded 3-D deformation fields between successive respiratory phases from which measures of regional lung function were determined. During the respiratory cycle, the lung volume changes and five different lobes of the lung (two in the left and three in the right lung) show different deformation yielding different strain and Jacobian maps. In this thesis, we determine the regional lung mechanics in the Lagrangian frame of reference through different respiratory phases, for example, Phase10 to 20, Phase10 to 30, Phase10 to 40, and Phase10 to 50. Single photon emission computed tomography (SPECT) lung imaging using radioactive tracers with SPECT ventilation and SPECT perfusion imaging also provides functional information. As part of an IRB-approved study therefore, we registered the max-inhale CT volume to both VSPECT and QSPECT data sets using the Demon\u27s non-rigid registration algorithm in patient subjects. Subsequently, statistical correlation between CT ventilation images (Jacobian and strain values), with both VSPECT and QSPECT was undertaken. Through statistical analysis with the Spearman\u27s rank correlation coefficient, we found that Jacobian values have the highest correlation with both VSPECT and QSPECT

Simulation of fluid dynamics and particle transport in a realistic human nasal cavity

Airflow and particle transport through the nasal cavity was studied using Computational Fluid Dynamics (CFD). A computational model of the human nasal cavity was reconstructed through CT scans. The process involved defining the airway outline through points in space that had to be fitted with a closed surface. The airflow was first simulated and detailed airflow structures such as local vortices, wall shear stresses, pressure drop and flow distribution were obtained. In terms of heat transfer the differences in the width of the airway especially in the frontal regions was found to be critical as the temperature difference was greatest and therefore heating of the air is expedited when the air is surrounded by the hotter walls. Understanding the effects of the airway geometry on the airflow patterns allows better predictions of particle transport through the airway. Inhalation of foreign particles is filtered by the nasal cilia to some degree as a defence mechanism of the airway. Particles such as asbestos fibres, pollen and diesel fumes can be considered as toxic and lead to health problems. These particles were introduced and the effects of particle morphology were considered by customising the particle trajectory equation. This mainly included the effects of the drag correlation and its shape factor. Local particle deposition sites, detailed deposition efficiencies and particle trajectories were obtained. High inertial particles tended to be filtered within the anterior regions of the cavity due to a change in direction of the airway as the air flow changes from vertical at the inlet to horizontal within the main nasal passage. Inhaled particles with pharmacological agents are often deliberately introduced into the nasal airway with a target delivery. The mucous lined airway that is highly vascular provides an avenue for drug delivery into the blood stream. An initial nasal spray experiment was performed to determine the parameters that were important for nasal spray drug delivery. The important parameters were determined to be the spray angle, initial particle velocity and particle swirl. It was found that particles were formed at a break-up length at a cone diameter greater than the spray nozzle diameter. The swirl fraction determined how much of the velocity magnitude went into a tangential component. By combining a swirling component along with a narrow spray into the main streamlines, greater penetration of larger particles into the nasal cavity may be possible. These parameters were then used as the boundary conditions for a parametric study into sprayed particle drug delivery within the CFD domain. The results were aimed to assist in the design of more efficient nasal sprays

Feature-driven Volume Visualization of Medical Imaging Data

Direct volume rendering (DVR) is a volume visualization technique that has been proved to be a very powerful tool in many scientific visualization domains. Diagnostic medical imaging is one such domain in which DVR provides new capabilities for the analysis of complex cases and improves the efficiency of image interpretation workflows. However, the full potential of DVR in the medical domain has not yet been realized. A major obstacle for a better integration of DVR in the medical domain is the time-consuming process to optimize the rendering parameters that are needed to generate diagnostically relevant visualizations in which the important features that are hidden in image volumes are clearly displayed, such as shape and spatial localization of tumors, its relationship with adjacent structures, and temporal changes in the tumors. In current workflows, clinicians must manually specify the transfer function (TF), view-point (camera), clipping planes, and other visual parameters. Another obstacle for the adoption of DVR to the medical domain is the ever increasing volume of imaging data. The advancement of imaging acquisition techniques has led to a rapid expansion in the size of the data, in the forms of higher resolutions, temporal imaging acquisition to track treatment responses over time, and an increase in the number of imaging modalities that are used for a single procedure. The manual specification of the rendering parameters under these circumstances is very challenging. This thesis proposes a set of innovative methods that visualize important features in multi-dimensional and multi-modality medical images by automatically or semi-automatically optimizing the rendering parameters. Our methods enable visualizations necessary for the diagnostic procedure in which 2D slice of interest (SOI) can be augmented with 3D anatomical contextual information to provide accurate spatial localization of 2D features in the SOI; the rendering parameters are automatically computed to guarantee the visibility of 3D features; and changes in 3D features can be tracked in temporal data under the constraint of consistent contextual information. We also present a method for the efficient computation of visibility histograms (VHs) using adaptive binning, which allows our optimal DVR to be automated and visualized in real-time. We evaluated our methods by producing visualizations for a variety of clinically relevant scenarios and imaging data sets. We also examined the computational performance of our methods for these scenarios

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Feature-driven Volume Visualization of Medical Imaging Data

Direct volume rendering (DVR) is a volume visualization technique that has been proved to be a very powerful tool in many scientific visualization domains. Diagnostic medical imaging is one such domain in which DVR provides new capabilities for the analysis of complex cases and improves the efficiency of image interpretation workflows. However, the full potential of DVR in the medical domain has not yet been realized. A major obstacle for a better integration of DVR in the medical domain is the time-consuming process to optimize the rendering parameters that are needed to generate diagnostically relevant visualizations in which the important features that are hidden in image volumes are clearly displayed, such as shape and spatial localization of tumors, its relationship with adjacent structures, and temporal changes in the tumors. In current workflows, clinicians must manually specify the transfer function (TF), view-point (camera), clipping planes, and other visual parameters. Another obstacle for the adoption of DVR to the medical domain is the ever increasing volume of imaging data. The advancement of imaging acquisition techniques has led to a rapid expansion in the size of the data, in the forms of higher resolutions, temporal imaging acquisition to track treatment responses over time, and an increase in the number of imaging modalities that are used for a single procedure. The manual specification of the rendering parameters under these circumstances is very challenging. This thesis proposes a set of innovative methods that visualize important features in multi-dimensional and multi-modality medical images by automatically or semi-automatically optimizing the rendering parameters. Our methods enable visualizations necessary for the diagnostic procedure in which 2D slice of interest (SOI) can be augmented with 3D anatomical contextual information to provide accurate spatial localization of 2D features in the SOI; the rendering parameters are automatically computed to guarantee the visibility of 3D features; and changes in 3D features can be tracked in temporal data under the constraint of consistent contextual information. We also present a method for the efficient computation of visibility histograms (VHs) using adaptive binning, which allows our optimal DVR to be automated and visualized in real-time. We evaluated our methods by producing visualizations for a variety of clinically relevant scenarios and imaging data sets. We also examined the computational performance of our methods for these scenarios

Adaptive Quantification and Subtyping of Pulmonary Emphysema on Computed Tomography

Pulmonary emphysema contributes to the chronic airflow limitation characteristic of chronic obstructive pulmonary disease (COPD), which is a leading cause of morbidity and mortality worldwide. Computed tomography (CT) has enabled in vivo assessment of pulmonary emphysema at the macroscopic level, and is commonly used to identify and assess the extent of the disease. During the past decade, the availability of CT imaging data has increased rapidly, while the image quality has continued to improve. High-resolution CT is extremely valuable both for patient diagnosis and for studying diseases at the population level. However, visual assessment of these large data sets is subjective, inefficient, and expensive. This has increased the demand for objective, automatic, and reproducible image analysis methods. For the assessment of pulmonary emphysema on CT, computational models usually aim either to give a measure of the extent of the disease, or to categorize the emphysema subtypes apparent in a scan. The standard methods for quantitating emphysema extent are widely used, but they remain sensitive to changes in imaging protocols and patient inspiration level. For computational subtyping of emphysema, the methods remain at a developmental stage, and one of the main challenges is the lack of reliable label data. Furthermore, the classic emphysema subtypes were defined on autopsy before the availability of CT and could be considered outdated. There is also no consensus on how to match the subtypes on autopsy to the varying emphysema patterns present on CT. This work presents two methodological improvements for analyzing emphysema on CT. For the assessment of emphysema extent, a novel probabilistic approach is introduced and evaluated on a longitudinal data set with varying imaging protocols. The presented model is shown to improve significantly compared to standard methods, particularly at the presence of differing noise levels. The approach is also applied on quantifying emphysema on a large data set of cardiac CT scans, and is shown to improve the prediction of emphysema extent on subsequent full-lung CT scans. The second major contribution of this work applies unsupervised learning to recognizing patterns of emphysema on CT. Instead of trying to reproduce the classic subtypes, the novel approach aims to capture the most dominant variations of lung structure pertaining to emphysema. While removing the reliance on visually assigned labels, the learned patterns are shown to represent different manifestations of emphysema with distinct appearances and regular spatial distributions. The clinical significance of the patterns is also demonstrated, along with high-level performance in the application of content-based image retrieval. The contributions of this work advance the analysis of emphysema on CT by applying novel machine learning approaches to increase the value of the available imaging data. Probabilistic methods improve from the crude standard methods that are currently used to quantitate emphysema, and the value of learning disease patterns directly from image data is demonstrated. The common framework relying on replicating visually assigned labels of outdated subtypes has not achieved widespread acceptance. The methodology presented in this work may have a substantial impact on how emphysema subtypes on CT are recognized and defined in the future