Machine learning for efficient recognition of anatomical structures and abnormalities in biomedical images

Three studies have been carried out to investigate new approaches to efficient image segmentation and anomaly detection. The first study investigates the use of deep learning in patch based segmentation. Current approaches to patch based segmentation use low level features such as the sum of squared differences between patches. We argue that better segmentation can be achieved by harnessing the power of deep neural networks. Currently these networks make extensive use of convolutional layers. However, we argue that in the context of patch based segmentation, convolutional layers have little advantage over the canonical artificial neural network architecture. This is because a patch is small, and does not need decomposition and thus will not benefit from convolution. Instead, we make use of the canonical architecture in which neurons only compute dot products, but also incorporate modern techniques of deep learning. The resulting classifier is much faster and less memory-hungry than convolution based networks. In a test application to the segmentation of hippocampus in human brain MR images, we significantly outperformed prior art with a median Dice score up to 90.98% at a near real-time speed (<1s). The second study is an investigation into mouse phenotyping, and develops a high-throughput framework to detect morphological abnormality in mouse embryo micro-CT images. Existing work in this line is centred on, either the detection of phenotype-specific features or comparative analytics. The former approach lacks generality and the latter can often fail, for example, when the abnormality is not associated with severe volume variation. Both these approaches often require image segmentation as a pre-requisite, which is very challenging when applied to embryo phenotyping. A new approach to this problem in which non-rigid registration is combined with robust principal component analysis (RPCA), is proposed. The new framework is able to efficiently perform abnormality detection in a batch of images. It is sensitive to both volumetric and non-volumetric variations, and does not require image segmentation. In a validation study, it successfully distinguished the abnormal VSD and polydactyly phenotypes from the normal, respectively, at 85.19% and 88.89% specificities, with 100% sensitivity in both cases. The third study investigates the RPCA technique in more depth. RPCA is an extension of PCA that tolerates certain levels of data distortion during feature extraction, and is able to decompose images into regular and singular components. It has previously been applied to many computer vision problems (e.g. video surveillance), attaining excellent performance. However these applications commonly rest on a critical condition: in the majority of images being processed, there is a background with very little variation. By contrast in biomedical imaging there is significant natural variation across different images, resulting from inter-subject variability and physiological movements. Non-rigid registration can go some way towards reducing this variance, but cannot eliminate it entirely. To address this problem we propose a modified framework (RPCA-P) that is able to incorporate natural variation priors and adjust outlier tolerance locally, so that voxels associated with structures of higher variability are compensated with a higher tolerance in regularity estimation. An experimental study was applied to the same mouse embryo micro-CT data, and notably improved the detection specificity to 94.12% for the VSD and 90.97% for the polydactyly, while maintaining the sensitivity at 100%.Open Acces

Representation Learning with Adversarial Latent Autoencoders

A large number of deep learning methods applied to computer vision problems require encoder-decoder maps. These methods include, but are not limited to, self-representation learning, generalization, few-shot learning, and novelty detection. Encoder-decoder maps are also useful for photo manipulation, photo editing, superresolution, etc. Encoder-decoder maps are typically learned using autoencoder networks.Traditionally, autoencoder reciprocity is achieved in the image-space using pixel-wisesimilarity loss, which has a widely known flaw of producing non-realistic reconstructions. This flaw is typical for the Variational Autoencoder (VAE) family and is not only limited to pixel-wise similarity losses, but is common to all methods relying upon the explicit maximum likelihood training paradigm, as opposed to an implicit one. Likelihood maximization, coupled with poor decoder distribution leads to poor or blurry reconstructions at best. Generative Adversarial Networks (GANs) on the other hand, perform an implicit maximization of the likelihood by solving a minimax game, thus bypassing the issues derived from the explicit maximization. This provides GAN architectures with remarkable generative power, enabling the generation of high-resolution images of humans, which are indistinguishable from real photos to the naked eye. However, GAN architectures lack inference capabilities, which makes them unsuitable for training encoder-decoder maps, effectively limiting their application space.We introduce an autoencoder architecture that (a) is free from the consequences ofmaximizing the likelihood directly, (b) produces reconstructions competitive in quality with state-of-the-art GAN architectures, and (c) allows learning disentangled representations, which makes it useful in a variety of problems. We show that the proposed architecture and training paradigm significantly improves the state-of-the-art in novelty and anomaly detection methods, it enables novel kinds of image manipulations, and has significant potential for other applications

Bayesian image restoration and bacteria detection in optical endomicroscopy

Optical microscopy systems can be used to obtain high-resolution microscopic images of tissue cultures and ex vivo tissue samples. This imaging technique can be translated for in vivo, in situ applications by using optical fibres and miniature optics. Fibred optical endomicroscopy (OEM) can enable optical biopsy in organs inaccessible by any other imaging systems, and hence can provide rapid and accurate diagnosis in a short time. The raw data the system produce is difficult to interpret as it is modulated by a fibre bundle pattern, producing what is called the “honeycomb effect”. Moreover, the data is further degraded due to the fibre core cross coupling problem. On the other hand, there is an unmet clinical need for automatic tools that can help the clinicians to detect fluorescently labelled bacteria in distal lung images. The aim of this thesis is to develop advanced image processing algorithms that can address the above mentioned problems. First, we provide a statistical model for the fibre core cross coupling problem and the sparse sampling by imaging fibre bundles (honeycomb artefact), which are formulated here as a restoration problem for the first time in the literature. We then introduce a non-linear interpolation method, based on Gaussian processes regression, in order to recover an interpretable scene from the deconvolved data. Second, we develop two bacteria detection algorithms, each of which provides different characteristics. The first approach considers joint formulation to the sparse coding and anomaly detection problems. The anomalies here are considered as candidate bacteria, which are annotated with the help of a trained clinician. Although this approach provides good detection performance and outperforms existing methods in the literature, the user has to carefully tune some crucial model parameters. Hence, we propose a more adaptive approach, for which a Bayesian framework is adopted. This approach not only outperforms the proposed supervised approach and existing methods in the literature but also provides computation time that competes with optimization-based methods

Localization and Navigation of the CoBots Over Long-term Deployments

For the last three years, we have developed and researched multiple collaborative robots, CoBots, which have been autonomously traversing our multi-floor buildings. We pursue the goal of long-term autonomy for indoor service mobile robots as the ability for them to be deployed indefinitely while they perform tasks in an evolving environment. The CoBots include several levels of autonomy, and in this paper we focus on their localization and navigation algorithms. We present the Corrective Gradient Refinement (CGR) algorithm, which refines the proposal distribution of the particle filter used for localization with sensor observations using analytically computed state space derivatives on a vector map. We also present the Fast Sampling Plane Filtering (FSPF) algorithm that extracts planar regions from depth images in real time. These planar regions are then projected onto the 2D vector map of the building, and along with the laser rangefinder observations, used with CGR for localization. For navigation, we present a hierarchical planner, which computes a topological policy using a graph representation of the environment, computes motion commands based on the topological policy, and then modifies the motion commands to side-step perceived obstacles. The continuous deployments of the CoBots over the course of one and a half years have provided us with logs of the CoBots traversing more than 130km over 1082 deployments, which we publish as a dataset consisting of more than 10 million laser scans. The logs show that although there have been continuous changes in the environment, the robots are robust to most of them, and there exist only a few locations where changes in the environment cause increased uncertainty in localization

Statistical Issues in Combining Multiple Genomic Studies: Quality Assessment, Dimension Reduction and Integration of Transcriptomic and Phenomic Data

Genomic meta-analysis has been applied to many biological problems to gain more power from increased sample sizes and to validate the result from an individual study. As for the study selection criteria, however, most literatures depend on qualitative or ad-hoc numerical methods, and there has not been an effort to develop a rigorous quantitative evaluation framework. In this thesis, we proposed several quantitative measures to assess the quality of a study for a meta-analysis. We have applied the proposed integrative criteria to multiple microarray studies to screen out inappropriate studies and also confirmed the necessity of proper exclusion criteria using real meta-analyses. By simulation studies, we showed the effectiveness and robustness of the proposed criteria. Secondly, we have investigated simultaneous dimension reduction frameworks for down-stream genomic meta-analysis. Currently, most microarray meta-analyses focus on detecting biomarkers; however, it is also valuable to seek a possibility of meta-analysis in unsupervised or supervised machine learning, particularly dimension reduction when multiple studies are combined. We proposed several simultaneous dimension reduction methods using principal component analysis (PCA). Using five examples of real microarray data, we showed the information gain obtained by adopting our proposed procedures in terms of better visualization and prediction accuracy. In the third component, we pursued a novel approach to elucidate undefined disease phenotypes between interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD). By applying unsupervised learning technique to both clinical phenotypes and gene expression data obtained from well characterized large number of cohort, we successfully showed the existence of intermediate phenotypic group who have both disease characteristics and divergent phenotypes in clinical and molecular features. Public health importance of our findings is that we showed current clinical definitions and classification do not account for the large number of patients having intermediate phenotypes or less common features that are often excluded from clinical trials and epidemiology reports