Deep learning-based improvement for the outcomes of glaucoma clinical trials

Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management. To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial

Biological model representation and analysis

In this thesis, we discuss solutions of phenotype description based on the microscopy image analysis to deal with biological problems both in 2D and 3D space. Our description of patterns goes beyond conventional features and helps to visualize the unseen in feature dataset. These solutions share several common processes which are based on similar principles. Furthermore, we notice that advanced features and classier strategies can help us improve the performance of the solutions. The biological problems that we have studied include the endocytosis routing using high-throughput screening in 2D and time and 3D geometrical representation from biological structures.China Scholarship CouncilComputer Systems, Imagery and Medi

Bayesian Model Based Tracking with Application to Cell Segmentation and Tracking

The goal of this research is to develop a model-based tracking framework with biomedical imaging applications. This is an interdisciplinary area of research with interests in machine vision, image processing, and biology. This thesis presents methods of image modeling, tracking, and data association applied to problems in multi-cellular image analysis, especially hematopoietic stem cell (HSC) images at the current stage. The focus of this research is on the development of a robust image analysis interface capable of detecting, locating, and tracking individual hematopoietic stem cells (HSCs), which proliferate and differentiate to different blood cell types continuously during their lifetime, and are of substantial interest in gene therapy, cancer, and stem-cell research. Such a system can be potentially employed in the future to track different groups of HSCs extracted from bone marrow and recognize the best candidates based on some biomedical-biological criteria. Selected candidates can further be used for bone marrow transplantation (BMT) which is a medical procedure for the treatment of various incurable diseases such as leukemia, lymphomas, aplastic anemia, immune deficiency disorders, multiple myeloma and some solid tumors. Tracking HSCs over time is a localization-based tracking problem which is one of the most challenging tracking problems to be solved. The proposed cell tracking system consists of three inter-related stages: i) Cell detection/localization, ii) The association of detected cells, iii) Background estimation/subtraction. that will be discussed in detail