Analysis of MRI for Knee Osteoarthritis using Machine Learning

Approximately 8.5 million people in the UK (13.5% of the population) have osteoarthritis (OA) in one or both knees, with more than 6 million people in the UK suffering with painful osteoarthritis of the knee. In addition, an ageing population implies that an estimated 17 million people (twice as many as in 2012) are likely to be living with OA by 2030. Despite this, there exists no disease modifying drugs for OA and structural OA in MRI is poorly characterised. This motivates research to develop biomarkers and tools to aid osteoarthritis diagnosis from MRI of the knee. Previously many solutions for learning biomarkers have relied upon hand-crafted features to characterise and diagnose osteoarthritis from MRI. The methods proposed in this thesis are scalable and use machine learning to characterise large populations of the OAI dataset, with one experiment applying an algorithm to over 10,000 images. Studies of this size enable subtle characteristics of the dataset to be learnt and model many variations within a population. We present data-driven algorithms to learn features to predict OA from the appearance of the articular cartilage. An unsupervised manifold learning algorithm is used to compute a low dimensional representation of knee MR data which we propose as an imaging marker of OA. Previous metrics introduced for OA diagnosis are loosely based on the research communities intuition of the structural causes of OA progression, including morphological measures of the articular cartilage such as the thickness and volume. We demonstrate that there is a strong correlation between traditional morphological measures of the articular cartilage and the biomarkers identified using the manifold learning algorithm that we propose (R 2 = 0.75). The algorithm is extended to create biomarkers for different regions and sequences. A combination of these markers is proposed to yield a diagnostic imaging biomarker with superior performance. The diagnostic biomarkers presented are shown to improve upon hand-crafted morphological measure of disease status presented in the literature, a linear discriminant analysis (LDA) classification for early stage diagnosis of knee osteoarthritis results with an AUC of 0.9. From the biomarker discovery experiments we identified that intensity based affine registration of knee MRIs is not sufficiently robust for large scale image analysis, approximately 5% of these registrations fail. We have developed fast algorithms to compute robust affine transformations of knee MRI, which enables accurate pairwise registrations in large datasets. We model the population of images as a non-linear manifold, a registration is defined by the shortest geodesic path over the manifold representation. We identify sources of error in our manifold representation and propose fast mitigation strategies by checking for consistency across the manifold and by utilising multiple paths. These mitigation strategies are shown to improve registration accuracy and can be computed in less than 2 seconds with current architecture.Open Acces

Landmark Localization, Feature Matching and Biomarker Discovery from Magnetic Resonance Images

The work presented in this thesis proposes several methods that can be roughly divided into three different categories: I) landmark localization in medical images, II) feature matching for image registration, and III) biomarker discovery in neuroimaging. The first part deals with the identification of anatomical landmarks. The motivation stems from the fact that the manual identification and labeling of these landmarks is very time consuming and prone to observer errors, especially when large datasets must be analyzed. In this thesis we present three methods to tackle this challenge: A landmark descriptor based on local self-similarities (SS), a subspace building framework based on manifold learning and a sparse coding landmark descriptor based on data-specific learned dictionary basis. The second part of this thesis deals with finding matching features between a pair of images. These matches can be used to perform a registration between them. Registration is a powerful tool that allows mapping images in a common space in order to aid in their analysis. Accurate registration can be challenging to achieve using intensity based registration algorithms. Here, a framework is proposed for learning correspondences in pairs of images by matching SS features and random sample and consensus (RANSAC) is employed as a robust model estimator to learn a deformation model based on feature matches. Finally, the third part of the thesis deals with biomarker discovery using machine learning. In this section a framework for feature extraction from learned low-dimensional subspaces that represent inter-subject variability is proposed. The manifold subspace is built using data-driven regions of interest (ROI). These regions are learned via sparse regression, with stability selection. Also, probabilistic distribution models for different stages in the disease trajectory are estimated for different class populations in the low-dimensional manifold and used to construct a probabilistic scoring function.Open Acces

Patch-based segmentation with spatial context for medical image analysis

Accurate segmentations in medical imaging form a crucial role in many applications from pa- tient diagnosis to population studies. As the amount of data generated from medical images increases, the ability to perform this task without human intervention becomes ever more de- sirable. One approach, known broadly as atlas-based segmentation, is to propagate labels from images which have already been manually labelled by clinical experts. Methods using this ap- proach have been shown to be e ective in many applications, demonstrating great potential for automatic labelling of large datasets. However, these methods usually require the use of image registration and are dependent on the outcome of the registration. Any registrations errors that occur are also propagated to the segmentation process and are likely to have an adverse e ect on segmentation accuracy. Recently, patch-based methods have been shown to allow a relaxation of the required image alignment, whilst achieving similar results. In general, these methods label each voxel of a target image by comparing the image patch centred on the voxel with neighbouring patches from an atlas library and assigning the most likely label according to the closest matches. The main contributions of this thesis focuses around this approach in providing accurate segmentation results whilst minimising the dependency on registration quality. In particular, this thesis proposes a novel kNN patch-based segmentation framework, which utilises both intensity and spatial information, and explore the use of spatial context in a diverse range of applications. The proposed methods extend the potential for patch-based segmentation to tolerate registration errors by rede ning the \locality" for patch selection and comparison, whilst also allowing similar looking patches from di erent anatomical structures to be di erentiated. The methods are evaluated on a wide variety of image datasets, ranging from the brain to the knees, demonstrating its potential with results which are competitive to state-of-the-art techniques.Open Acces

Accurate, Fast and Controllable Image and Point Cloud Registration

Registration is the process of establishing spatial correspondences between two objects. Many downstream tasks, e.g, in image analysis, shape animation, can make use of these spatial correspondences. A variety of registration approaches have been developed over the last decades, but only recently registration approaches have been developed that make use of and can easily process the large data samples of the big data era. On the one hand, traditional optimization-based approaches are too slow and cannot take advantage of very large data sets. On the other hand, registration users expect more controllable and accurate solutions since most downstream tasks, e.g., facial animation and 3D reconstruction, increasingly rely on highly precise spatial correspondences. In recent years, deep network registration approaches have become popular as learning-based approaches are fast and can benefit from large-scale data during network training. However, how to make such deep-learning-based approached accurate and controllable is still a challenging problem that is far from being completely solved. This thesis explores fast, accurate and controllable solutions for image and point cloud registration. Specifically, for image registration, we first improve the accuracy of deep-learning-based approaches by introducing a general framework that consists of affine and non-parametric registration for both global and local deformation. We then design a more controllable image registration approach that image regions could be regularized differently according to their local attributes. For point cloud registration, existing works either are limited to small-scale problems, hardly handle complicated transformations or are slow to solve. We thus develop fast, accurate and controllable solutions for large-scale real-world registration problems via integrating optimal transport with deep geometric learning.Doctor of Philosoph

TOWARD SOLVING GROUPWISE MEDICAL IMAGE ANALYSIS PROBLEMS WITH DEEP LEARNING

Image regression, atlas building, and multi-atlas segmentation are three groupwise medical image analysis problems extended from image registration. These three problems are challenging because of the difficulty in establishing spatial correspondences and the associated high computational cost. Specifically, most previous methods are computationally costly as they are optimization-based approaches. Hence fast and accurate approaches are highly desirable. This dissertation addresses the following problems concerning the three groupwise medical im- age analysis problems: (1) fast and reliable geodesic regression for image time series; (2) joint atlas building and diffeomorphic registration learning; (3) efficient and accurate label fusion for multi-atlas segmentation; and (4) spatially localized probability calibration for semantic segmentation networks. Specifically, the contributions in this thesis are as follows: (1) A fast predictive simple geodesic regression approach is proposed to capture the frequently subtle deformation trends of longitudinal image data. (2) A new deep learning model that jointly builds an atlas and learns the diffeomorphic registrations in both the atlas-to-image and the image-to-atlas directions is developed. (3) A novel deep learning label fusion method (VoteNet) that locally identifies sets of trustworthy atlases is presented; and several ways to improve the performance under the VoteNet based multi-atlas segmentation framework are explored. (4) A learning-based local temperature scaling method that predicts a separate temperature scale for each pixel/voxel is designed. The resulting post-processing approach is accuracy preserving and is theoretically guaranteed to be effective.Doctor of Philosoph

Automatic Localized Analysis of Longitudinal Cartilage Changes

Osteoarthritis (OA) is the most common form of arthritis; it is characterized by the loss of cartilage. Automatic quantitative methods are needed to screen large image databases to assess changes in cartilage morphology. This dissertation presents an automatic analysis method to quantitatively analyze longitudinal cartilage changes from knee magnetic resonance (MR) images. A novel robust automatic cartilage segmentation method is proposed to overcome the limitations of existing cartilage segmentation methods. The dissertation presents a new and general convex three-label segmentation approach to ensure the separation of touching objects, i.e., femoral and tibial cartilage. Anisotropic spatial regularization is introduced to avoid over-regularization by isotropic regularization on thin objects. Temporal regularization is further incorporated to encourage temporally-consistent segmentations across time points for longitudinal data. The state-of-the-art analysis of cartilage changes relies on the subdivision of car- tilage, which is coarse and purely geometric whereas cartilage loss is a local thinning process and exhibits spatial non-uniformity. A novel statistical analysis method is proposed to study localized longitudinal cartilage thickness changes by establishing spatial correspondences across time and between subjects. The method is general and can be applied to other nonuniform morphological changes in other diseases.Doctor of Philosoph

Advanced Algorithms for 3D Medical Image Data Fusion in Specific Medical Problems

Fúze obrazu je dnes jednou z nejběžnějších avšak stále velmi diskutovanou oblastí v lékařském zobrazování a hraje důležitou roli ve všech oblastech lékařské péče jako je diagnóza, léčba a chirurgie. V této dizertační práci jsou představeny tři projekty, které jsou velmi úzce spojeny s oblastí fúze medicínských dat. První projekt pojednává o 3D CT subtrakční angiografii dolních končetin. V práci je využito kombinace kontrastních a nekontrastních dat pro získání kompletního cévního stromu. Druhý projekt se zabývá fúzí DTI a T1 váhovaných MRI dat mozku. Cílem tohoto projektu je zkombinovat stukturální a funkční informace, které umožňují zlepšit znalosti konektivity v mozkové tkáni. Třetí projekt se zabývá metastázemi v CT časových datech páteře. Tento projekt je zaměřen na studium vývoje metastáz uvnitř obratlů ve fúzované časové řadě snímků. Tato dizertační práce představuje novou metodologii pro klasifikaci těchto metastáz. Všechny projekty zmíněné v této dizertační práci byly řešeny v rámci pracovní skupiny zabývající se analýzou lékařských dat, kterou vedl pan Prof. Jiří Jan. Tato dizertační práce obsahuje registrační část prvního a klasifikační část třetího projektu. Druhý projekt je představen kompletně. Další část prvního a třetího projektu, obsahující specifické předzpracování dat, jsou obsaženy v disertační práci mého kolegy Ing. Romana Petera.Image fusion is one of today´s most common and still challenging tasks in medical imaging and it plays crucial role in all areas of medical care such as diagnosis, treatment and surgery. Three projects crucially dependent on image fusion are introduced in this thesis. The first project deals with the 3D CT subtraction angiography of lower limbs. It combines pre-contrast and contrast enhanced data to extract the blood vessel tree. The second project fuses the DTI and T1-weighted MRI brain data. The aim of this project is to combine the brain structural and functional information that purvey improved knowledge about intrinsic brain connectivity. The third project deals with the time series of CT spine data where the metastases occur. In this project the progression of metastases within the vertebrae is studied based on fusion of the successive elements of the image series. This thesis introduces new methodology of classifying metastatic tissue. All the projects mentioned in this thesis have been solved by the medical image analysis group led by Prof. Jiří Jan. This dissertation concerns primarily the registration part of the first project and the classification part of the third project. The second project is described completely. The other parts of the first and third project, including the specific preprocessing of the data, are introduced in detail in the dissertation thesis of my colleague Roman Peter, M.Sc.