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

Machine learning in orthopedics: a literature review

In this paper we present the findings of a systematic literature review covering the articles published in the last two decades in which the authors described the application of a machine learning technique and method to an orthopedic problem or purpose. By searching both in the Scopus and Medline databases, we retrieved, screened and analyzed the content of 70 journal articles, and coded these resources following an iterative method within a Grounded Theory approach. We report the survey findings by outlining the articles\u2019 content in terms of the main machine learning techniques mentioned therein, the orthopedic application domains, the source data and the quality of their predictive performance

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

Machine Learning in Orthopedics: A Literature Review

In this paper we present the findings of a systematic literature review covering the articles published in the last two decades in which the authors described the application of a machine learning technique and method to an orthopedic problem or purpose. By searching both in the Scopus and Medline databases, we retrieved, screened and analyzed the content of 70 journal articles, and coded these resources following an iterative method within a Grounded Theory approach. We report the survey findings by outlining the articles' content in terms of the main machine learning techniques mentioned therein, the orthopedic application domains, the source data and the quality of their predictive performance

ADVANCED STATISTICAL LEARNING METHODS FOR HETEROGENEOUS MEDICAL IMAGING DATA

Most neuro-related diseases and disabling diseases display significant heterogeneity at the imaging and clinical scales. Characterizing such heterogeneity could transform our understanding of the etiology of these conditions and inspire new approaches to urgently needed preventions, diagnoses, and treatments. However, existing statistical methods face major challenges in delineating such heterogeneity at subject, group and study levels. In order to address these challenges, this work proposes several statistical learning methods for heterogeneous imaging data with different structures. First, we propose a dynamic spatial random effects model for longitudinal imaging dataset, which aims at characterizing both the imaging intensity progression and the temporal-spatial heterogeneity of diseased regions across subjects and time. The key components of proposed model include a spatial random effects model and a dynamic conditional random field model. The proposed model can effectively detect the dynamic diseased regions in each patient and present a dynamic statistical disease mapping within each subpopulation of interest. Second, to address the group level heterogeneity in non-Euclidean data, we develop a penalized model-based clustering framework to cluster high dimensional manifold data in symmetric spaces. Specifically, a mixture of geodesic factor analyzers is proposed with mixing proportions determined through a logistic model and Riemannian normal distribution in each component for data in symmetric spaces. Penalized likelihood approaches are used to realize variable selection procedures. We apply the proposed model to the ADNI hippocampal surface data, which shows excellent clustering performance and remarkably reveal meaningful clusters in the mixed population with controls and subjects with AD. Finally, to consider the potential heterogeneity caused by unobserved environmental, demographic and technical factors, we treat the imaging data as functional responses, and set up a surrogate variable analysis framework in functional linear models. A functional latent factor regression model is proposed. The confounding factors and the bias of local linear estimators caused by the confounding factors can be estimated and removed using singular value decomposition on residuals. We further develop a test for linear hypotheses of primary coefficient functions. Both simulation studies and ADNI hippocampal surface data analysis are conducted to show the performance of proposed method.Doctor of Philosoph

Patient-Specific Implants in Musculoskeletal (Orthopedic) Surgery

Most of the treatments in medicine are patient specific, aren’t they? So why should we bother with individualizing implants if we adapt our therapy to patients anyway? Looking at the neighboring field of oncologic treatment, you would not question the fact that individualization of tumor therapy with personalized antibodies has led to the thriving of this field in terms of success in patient survival and positive responses to alternatives for conventional treatments. Regarding the latest cutting-edge developments in orthopedic surgery and biotechnology, including new imaging techniques and 3D-printing of bone substitutes as well as implants, we do have an armamentarium available to stimulate the race for innovation in medicine. This Special Issue of Journal of Personalized Medicine will gather all relevant new and developed techniques already in clinical practice. Examples include the developments in revision arthroplasty and tumor (pelvic replacement) surgery to recreate individual defects, individualized implants for primary arthroplasty to establish physiological joint kinematics, and personalized implants in fracture treatment, to name but a few