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

Finite element modeling of soft tissue deformation.

Computer-aided minimally invasive surgery (MIS) has progressed significantly in the last decade and it has great potential in surgical planning and operations. To limit the damage to nearby healthy tissue, accurate modeling is required of the mechanical behavior of a target soft tissue subject to surgical manipulations. Therefore, the study of soft tissue deformations is important for computer-aided (MIS) in surgical planning and operation, or in developing surgical simulation tools or systems. The image acquisition facilities are also important for prediction accuracy. This dissertation addresses partial differential and integral equations (PDIE) based biomechanical modeling of soft tissue deformations incorporating the specific material properties to characterize the soft tissue responses for certain human interface behaviors. To achieve accurate simulation of real tissue deformations, several biomechanical finite element (FE) models are proposed to characterize liver tissue. The contribution of this work is in theoretical and practical aspects of tissue modeling. High resolution imaging techniques of Micro Computed Tomography (Micro-CT) and Cone Beam Computed Tomography (CBCT) imaging are first proposed to study soft tissue deformation in this dissertation. These high resolution imaging techniques can detect the tissue deformation details in the contact region between the tissue and the probe for small force loads which would be applied to a surgical probe used. Traditional imaging techniques in clinics can only achieve low image resolutions. Very small force loads seen in these procedures can only yield tissue deformation on the few millimeters to submillimeter scale. Small variations are hardly to detect. Furthermore, if a model is validated using high resolution images, it implies that the model is true in using the same model for low resolution imaging facilities. The reverse cannot be true since the small variations at the sub-millimeter level cannot be detected. In this dissertation, liver tissue deformations, surface morphological changes, and volume variations are explored and compared from simulations and experiments. The contributions of the dissertation are as follows. For liver tissue, for small force loads (5 grams to tens of grams), the linear elastic model and the neo-Hooke\u27s hyperelastic model are applied and shown to yield some discrepancies among them in simulations and discrepancies between simulations and experiments. The proposed finite element models are verified for liver tissue. A general FE modeling validation system is proposed to verify the applicability of FE models to the soft tissue deformation study. The validation of some FE models is performed visually and quantitatively in several ways in comparison with the actual experimental results. Comparisons among these models are also performed to show their advantages and disadvantages. The method or verification system can be applied for other soft tissues for the finite element analysis of the soft tissue deformation. For brain tissue, an elasticity based model was proposed previously employing local elasticity and Poisson\u27s ratio. It is validated by intraoperative images to show more accurate prediction of brain deformation than the linear elastic model. FE analysis of brain ventricle shape changes was also performed to capture the dynamic variation of the ventricles in author\u27s other works. There, for the safety reasons, the images for brain deformation modeling were from Magnetic Resonance Imaging (MRI) scanning which have been used for brain scanning. The measurement process of material properties involves the tissue desiccation, machine limits, human operation errors, and time factors. The acquired material parameters from measurement devices may have some difference from the tissue used in real state of experiments. Therefore, an experimental and simulation based method to inversely evaluate the material parameters is proposed and compare

Real-time Biomechanical Modeling for Intraoperative Soft Tissue Registration

Computer assisted surgery systems intraoperatively support the surgeon by providing information on the location of hidden risk and target structures during surgery. However, soft tissue deformations make intraoperative registration (and thus intraoperative navigation) difficult. In this work, a novel, biomechanics based approach for real-time soft tissue registration from sparse intraoperative sensor data such as stereo endoscopic images is presented to overcome this problem

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Improving Dose-Response Correlations for Locally Advanced NSCLC Patients Treated with IMRT or PSPT

The standard of care for locally advanced non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy. Despite recent advancements in radiation delivery methods, the median survival time of NSCLC patients remains below 28 months. Higher tumor dose has been found to increase survival but also a higher rate of radiation pneumonitis (RP) that affects breathing capability. In fear of such toxicity, less-aggressive treatment plans are often clinically preferred, leading to metastasis and recurrence. Therefore, accurate RP prediction is crucial to ensure tumor coverage to improve treatment outcome. Current models have associated RP with increased dose but with limited accuracy as they lack spatial correlation between accurate dose representation and quantitative RP representation. These models represent lung tissue damage with radiation dose distribution planned pre-treatment, which assumes a fixed patient geometry and inevitably renders imprecise dose delivery due to intra-fractional breathing motion and inter-fractional anatomy response. Additionally, current models employ whole-lung dose metrics as the contributing factor to RP as a qualitative, binary outcome but these global dose metrics discard microscopic, voxel-(3D pixel)-level information and prevent spatial correlations with quantitative RP representation. To tackle these limitations, we developed advanced deformable image registration (DIR) techniques that registered corresponding anatomical voxels between images for tracking and accumulating dose throughout treatment. DIR also enabled voxel-level dose-response correlation when CT image density change (IDC) was used to quantify RP. We hypothesized that more accurate estimates of biologically effective dose distributions actually delivered, achieved through (a) dose accumulation using deformable registration of weekly 4DCT images acquired over the course or radiotherapy and (b) the incorporation of variable relative biological effectiveness (RBE), would lead to statistically and clinically significant improvement in the correlation of RP with biologically effective dose distributions. Our work resulted in a robust intra-4DCT and inter-4DCT DIR workflow, with the accuracy meeting AAPM TG-132 recommendations for clinical implementation of DIR. The automated DIR workflow allowed us to develop a fully automated 4DCT-based dose accumulation pipeline in RayStation (RaySearch Laboratories, Stockholm, Sweden). With a sample of 67 IMRT patients, our results showed that the accumulated dose was statistically different than the planned dose across the entire cohort with an average MLD increase of ~1 Gy and clinically different for individual patients where 16% resulted in difference in the score of the normal tissue complication probability (NTCP) using an established, clinically used model, which could qualify the patients for treatment planning re-evaluation. Lastly, we associated dose difference with accuracy difference by establishing and comparing voxel-level dose-IDC correlations and concluded that the accumulated dose better described the localized damage, thereby a closer representation of the delivered dose. Using the same dose-response correlation strategy, we plotted the dose-IDC relationships for both photon patients (N = 51) and proton patients (N = 67), we measured the variable proton RBE values to be 3.07–1.27 from 9–52 Gy proton voxels. With the measured RBE values, we fitted an established variable proton RBE model with pseudo-R2 of 0.98. Therefore, our results led to statistically and clinically significant improvement in the correlation of RP with accumulated and biologically effective dose distributions and demonstrated the potential of incorporating the effect of anatomical change and biological damage in RP prediction models

A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications.publishedVersio

Growth, modelling and remodelling of cardiac tissue: a multiphase approach

Rheumatic heart disease (RHD) is identified as a serious health concern in developing countries, specifically amongst young individuals, accounting for between 250 000 and 1.4 million deaths annually. As such, the attention of this research is initially placed on the importance of the development of a cardiac analysis toolbox with functionality for pathophysiological analysis of the disease. Subsequently, in order to further the understanding of the mechanisms of the disease as linked to cardiomyocyte growth and remodelling of the microstructure, a continuum bi-phasic model applicable to cardiac tissue is formulated based on the theory of porous media (TPM). This makes it possible to account for interactions and contributions of multiple phases of constituent materials, which in computational cardiac modelling are the solid phase - the cardiac tissue - and the liquid phase - blood and interstitial uid. Subsequent attention is paid to the cardiac model development in order to implement a sound base on which to add strain-driven phase transition via a mass supply function proposed within this study. To this end, based on thermodynamical restrictions, constitutive relations are proposed for stress, permeability, seepage velocity, mass supply and interaction forces such as friction. The approach is implemented in the in-house computational cardiac mechanics toolbox SESKA which supports finite element as well as Element- free Galerkin-based approximations. This investigation considers the passive and active non-linear elastic material behaviour of the myocardium of the left ventricle coupled with porous media theory, along with an an additional coupling to the haemodynamics of the circulatory system, facilitating modelling of the full cardiac cycle. As such, an initial cardiac growth and remodelling computer model is developed as an initial step to computational modelling of the adverse effects of RHD and other similar in ammatory heart diseases, with the potential to limit the invasiveness and risk of in-vivo patient studies. A patient specific case study is conducted, making use of cardiovascular magnetic resonance scans taken over a period of two years from a patient affected by RHD to generate realistic 3D computer models, from which information is drawn with regards to the pathophysiological behaviour of the disease

Variational Methods in Shape Space

This dissertation deals with the application of variational methods in spaces of geometric shapes. In particular, the treated topics include shape averaging, principal component analysis in shape space, computation of geodesic paths in shape space, as well as shape optimisation. Chapter 1 provides a brief overview over the employed models of shape space. Geometric shapes are identified with two- or three-dimensional, deformable objects. Deformations will be described via physical models; in particular, the objects will be interpreted as consisting of either a hyperelastic solid or a viscous liquid material. Furthermore, the description of shapes via phase fields or level sets is briefly introduced. Chapter 2 reviews different and related approaches to shape space modelling. References to related topics in image segmentation and registration are also provided. Finally, the relevant shape optimisation literature is introduced. Chapter 3 recapitulates the employed concepts from continuum mechanics and phase field modelling and states basic theoretical results needed for the later analysis. Chapter 4 addresses the computation of shape averages, based on a hyperelastic notion of shape dissimilarity: The dissimilarity between two shapes is measured as the minimum deformation energy required to deform the first into the second shape. A corresponding phase-field model is introduced, analysed, and finally implemented numerically via finite elements. A principal component analysis of shapes, which is consistent with the previously introduced average, is considered in Chapter 5. Elastic boundary stresses on the average shape are used as representatives of the input shapes in a linear vector space. On these linear representatives, a standard principal component analysis can be performed, where the employed covariance metric should be properly chosen to depend on the input shapes. Chapter 6 interprets shapes as belonging to objects made of a viscous liquid and correspondingly defines geodesic paths between shapes. The energy of a path is given as the total physical dissipation during the deformation of an object along the path. A rigid body motion invariant time discretisation is achieved by approximating the dissipation along a path segment by the deformation energy of a small solid deformation. The numerical implementation is based on level sets. Chapter 7 is concerned with the optimisation of the geometry and topology of solid structures that are subject to a mechanical load. Given the load configuration, the structure rigidity, its volume, and its surface area shall be optimally balanced. A phase field model is devised and analysed for this purpose. In this context, the use of nonlinear elasticity allows to detect buckling phenomena which would be ignored in linearised elasticity

Exploring variability in medical imaging

Although recent successes of deep learning and novel machine learning techniques improved the perfor- mance of classification and (anomaly) detection in computer vision problems, the application of these methods in medical imaging pipeline remains a very challenging task. One of the main reasons for this is the amount of variability that is encountered and encapsulated in human anatomy and subsequently reflected in medical images. This fundamental factor impacts most stages in modern medical imaging processing pipelines. Variability of human anatomy makes it virtually impossible to build large datasets for each disease with labels and annotation for fully supervised machine learning. An efficient way to cope with this is to try and learn only from normal samples. Such data is much easier to collect. A case study of such an automatic anomaly detection system based on normative learning is presented in this work. We present a framework for detecting fetal cardiac anomalies during ultrasound screening using generative models, which are trained only utilising normal/healthy subjects. However, despite the significant improvement in automatic abnormality detection systems, clinical routine continues to rely exclusively on the contribution of overburdened medical experts to diagnosis and localise abnormalities. Integrating human expert knowledge into the medical imaging processing pipeline entails uncertainty which is mainly correlated with inter-observer variability. From the per- spective of building an automated medical imaging system, it is still an open issue, to what extent this kind of variability and the resulting uncertainty are introduced during the training of a model and how it affects the final performance of the task. Consequently, it is very important to explore the effect of inter-observer variability both, on the reliable estimation of model’s uncertainty, as well as on the model’s performance in a specific machine learning task. A thorough investigation of this issue is presented in this work by leveraging automated estimates for machine learning model uncertainty, inter-observer variability and segmentation task performance in lung CT scan images. Finally, a presentation of an overview of the existing anomaly detection methods in medical imaging was attempted. This state-of-the-art survey includes both conventional pattern recognition methods and deep learning based methods. It is one of the first literature surveys attempted in the specific research area.Open Acces