Enhanced retinal image registration accuracy using expectation maximisation and variable bin-sized mutual information

While retinal images (RI) assist in the diagnosis of various eye conditions and diseases such as glaucoma and diabetic retinopathy, their innate features including low contrast homogeneous and nonuniformly illuminated regions, present a particular challenge for retinal image registration (RIR). Recently, the hybrid similarity measure, Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) has been proposed for RIR. This paper investigates incorporating various fixed and adaptive bin size selection strategies to estimate the probability distribution in the mutual information (MI) stage of EMPCA-MI, and analyses their corresponding effect upon RIR performance. Experimental results using a clinical mono-modal RI dataset confirms that adaptive bin size selection consistently provides both lower RIR errors and superior robustness compared to the empirically determined fixed bin sizes

A Hybrid Similarity Measure Framework for Multimodal Medical Image Registration

Medical imaging is widely used today to facilitate both disease diagnosis and treatment planning practice, with a key prerequisite being the systematic process of medical image registration (MIR) to align either mono or multimodal images of different anatomical parts of the human body. MIR utilises a similarity measure (SM) to quantify the level of spatial alignment and is particularly demanding due to the presence of inherent modality characteristics like intensity non-uniformities (INU) in magnetic resonance images and large homogeneous non-vascular regions in retinal images. While various intensity and feature-based SMs exist for MIR, mutual information (MI) has become established because of its computational efficiency and ability to register multimodal images. It is however, very sensitive to interpolation artefacts in the presence of INU with noise and can be compromised when overlapping areas are small. Recently MI-based hybrid variants which combine regional features with intensity have emerged, though these incur high dimensionality and large computational overheads. To address these challenges and secure accurate, efficient and robust registration of images containing high INU, noise and large homogeneous regions, this thesis presents a new hybrid SM framework for 2D multimodal rigid MIR. The framework consistently provides superior quantitative and qualitative performance, while offering a uniquely flexible design trade-off between registration accuracy and computational time. It makes three significant technical contributions to the field: i) An expectation maximisation-based principal component analysis with mutual information (EMPCA-MI) framework incorporating neighbourhood feature information; ii) Two innovative enhancements to reduce information redundancy and improve MI computational efficiency; and iii) an adaptive algorithm to select the most significant principal components for feature selection. The thesis findings conclusively confirm the hybrid SM framework offers an accurate and robust 2D registration solution for challenging multimodal medical imaging datasets, while its inherent flexibility means it can also be extended to the 3D registration domain

Multimodal retinal image registration using a fast principal component analysis hybrid-based similarity measure

Multimodal retinal images (RI) are extensively used for analysing various eye diseases and conditions such as myopia and diabetic retinopathy. The incorporation of either two or more RI modalities provides complementary structure information in the presence of non-uniform illumination and low-contrast homogeneous regions. It also presents significant challenges for retinal image registration (RIR). This paper investigates how the Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) algorithm can effectively achieve multimodal RIR. This iterative hybrid-based similarity measure combines spatial features with mutual information to provide enhanced registration without recourse to either segmentation or feature extraction. Experimental results for clinical multimodal RI datasets comprising colour fundus and scanning laser ophthalmoscope images confirm EMPCA-MI is able to consistently afford superior numerical and qualitative registration performance compared with existing RIR techniques, such as the bifurcation structures method

Biologically-inspired robust motion segmentation using mutual information

This paper presents a neuroscience inspired information theoretic approach to motion segmentation. Robust motion segmentation represents a fundamental first stage in many surveillance tasks. As an alternative to widely adopted individual segmentation approaches, which are challenged in different ways by imagery exhibiting a wide range of environmental variation and irrelevant motion, this paper presents a new biologically-inspired approach which computes the multivariate mutual information between multiple complementary motion segmentation outputs. Performance evaluation across a range of datasets and against competing segmentation methods demonstrates robust performance

NON-INVASIVE IMAGE ENHANCEMENT OF COLOUR RETINAL FUNDUS IMAGES FOR A COMPUTERISED DIABETIC RETINOPATHY MONITORING AND GRADING SYSTEM

Diabetic Retinopathy (DR) is a sight threatening complication due to diabetes mellitus affecting the retina. The pathologies of DR can be monitored by analysing colour fundus images. However, the low and varied contrast between retinal vessels and the background in colour fundus images remains an impediment to visual analysis in particular in analysing tiny retinal vessels and capillary networks. To circumvent this problem, fundus fluorescein angiography (FF A) that improves the image contrast is used. Unfortunately, it is an invasive procedure (injection of contrast dyes) that leads to other physiological problems and in the worst case may cause death. The objective of this research is to develop a non-invasive digital Image enhancement scheme that can overcome the problem of the varied and low contrast colour fundus images in order that the contrast produced is comparable to the invasive fluorescein method, and without introducing noise or artefacts. The developed image enhancement algorithm (called RETICA) is incorporated into a newly developed computerised DR system (called RETINO) that is capable to monitor and grade DR severity using colour fundus images. RETINO grades DR severity into five stages, namely No DR, Mild Non Proliferative DR (NPDR), Moderate NPDR, Severe NPDR and Proliferative DR (PDR) by enhancing the quality of digital colour fundus image using RETICA in the macular region and analysing the enlargement of the foveal avascular zone (F AZ), a region devoid of retinal vessels in the macular region. The importance of this research is to improve image quality in order to increase the accuracy, sensitivity and specificity of DR diagnosis, and to enable DR grading through either direct observation or computer assisted diagnosis system

Snapshot spectral imaging using image replication and birefringent interferometry : principles and applications

This thesis explores the image-replicating imaging spectrometer (IRIS). This relatively recent invention is a two-dimensional, snapshot spectral-imaging technology, capable of recording the spectral and spatial data from a scene instantaneously. Whereas conventional spectral-imaging technologies require multiple detector frames to record the entire data set, IRIS is able to record the data set in a single frame, a capability which is useful for highly dynamic scenes. The IRIS concept and the design of IRIS systems are explained in detail, and constraints on the performance of IRIS are determined. Practical issue in the use of IRIS systems are identi ed and solutions are identi ed and appraised. Some applications of IRIS are also shown, demonstrating its viability as a spectral imaging technology. Novel aspects of this work include the re nement of the IRIS design, demonstration of a registration algorithm for IRIS, designs for achromatic Wollaston prisms, a comparison of the IRIS technology with conventional spectral imaging technologies, and the application of IRIS to practical problems.Engineering and Physical Sciences Research Council (EPSRC)Selex Galile

Automatic analysis of medical images for change detection in prostate cancer

Prostate cancer is the most common cancer and second most common cause of cancer death in men in the UK. However, the patient risk from the cancer can vary considerably, and the widespread use of prostate-specific antigen (PSA) screening has led to over-diagnosis and over-treatment of low-grade tumours. It is therefore important to be able to differentiate high-grade prostate cancer from the slowly- growing, low-grade cancer. Many of these men with low-grade cancer are placed on active surveillance (AS), which involves constant monitoring and intervention for risk reclassification, relying increasingly on magnetic resonance imaging (MRI) to detect disease progression, in addition to TRUS-guided biopsies which are the routine clinical standard method to use. This results in a need for new tools to process these images. For this purpose, it is important to have a good TRUS-MR registration so corresponding anatomy can be located accurately between the two. Automatic segmentation of the prostate gland on both modalities reduces some of the challenges of the registration, such as patient motion, tissue deformation, and the time of the procedure. This thesis focuses on the use of deep learning methods, specifically convolutional neural networks (CNNs), for prostate cancer management. Chapters 4 and 5 investigated the use of CNNs for both TRUS and MRI prostate gland segmentation, and reported high segmentation accuracies for both, Dice Score Coefficients (DSC) of 0.89 for TRUS segmentations and DSCs between 0.84-0.89 for MRI prostate gland segmentation using a range of networks. Chapter 5 also investigated the impact of these segmentation scores on more clinically relevant measures, such as MRI-TRUS registration errors and volume measures, showing that a statistically significant difference in DSCs did not lead to a statistically significant difference in the clinical measures using these segmentations. The potential of these algorithms in commercial and clinical systems are summarised and the use of the MRI prostate gland segmentation in the application of radiological prostate cancer progression prediction for AS patients are investigated and discussed in Chapter 8, which shows statistically significant improvements in accuracy when using spatial priors in the form of prostate segmentations (0.63 ± 0.16 vs. 0.82 ± 0.18 when comparing whole prostate MRI vs. only prostate gland region, respectively)

Deep Learning with Limited Labels for Medical Imaging

Recent advancements in deep learning-based AI technologies provide an automatic tool to revolutionise medical image computing. Training a deep learning model requires a large amount of labelled data. Acquiring labels for medical images is extremely challenging due to the high cost in terms of both money and time, especially for the pixel-wise segmentation task of volumetric medical scans. However, obtaining unlabelled medical scans is relatively easier compared to acquiring labels for those images. This work addresses the pervasive issue of limited labels in training deep learning models for medical imaging. It begins by exploring different strategies of entropy regularisation in the joint training of labelled and unlabelled data to reduce the time and cost associated with manual labelling for medical image segmentation. Of particular interest are consistency regularisation and pseudo labelling. Specifically, this work proposes a well-calibrated semi-supervised segmentation framework that utilises consistency regularisation on different morphological feature perturbations, representing a significant step towards safer AI in medical imaging. Furthermore, it reformulates pseudo labelling in semi-supervised learning as an Expectation-Maximisation framework. Building upon this new formulation, the work explains the empirical successes of pseudo labelling and introduces a generalisation of the technique, accompanied by variational inference to learn its true posterior distribution. The applications of pseudo labelling in segmentation tasks are also presented. Lastly, this work explores unsupervised deep learning for parameter estimation of diffusion MRI signals, employing a hierarchical variational clustering framework and representation learning

Incorporating spatial and temporal information for microaneurysm detection in retinal images

The retina of the human eye has the potential to reveal crucial information about several diseases such as diabetes. Several signs such as microaneurysms (MA) manifest themselves as early indicators of Diabetic Retinopathy (DR). Detection of these early signs is important from a clinical perspective in order to suggest appropriate treatment for DR patients. This work aims to improve the detection accuracy of MAs in colour fundus images. While it is expected that multiple images per eye are available in a clinical setup, proposed segmentation algorithms in the literature do not make use of these multiple images. This work introduces a novel MA detection algorithm and a framework for combining spatial and temporal images. A new MA detection method has been proposed which uses a Gaussian matched filter and an ensemble classifier with 70 features for the detection of candidates. The proposed method was evaluated on three public datasets (171 images in total) and has shown improvement in performance for two of the sets when compared to a state-of-the-art method. For lesion-based performance, the proposed method has achieved Retinopathy Online Challenge (ROC) scores of 0.3923, 2109 and 0.1523 in the MESSIDOR, DIARETDB1 and ROC datasets respectively. Based on the ensemble algorithm, a framework for the information combination is developed and consists of image alignment, detecting candidates with likelihood scores, matching candidates from aligned images, and finally fusing the scores from the aligned image pairs. This framework is used to combine information both spatially and temporally. A dataset of 320 images that consists of both spatial and temporal pairs was used for the evaluation. An improvement of performance by 2% is shown after combining spatial information. The framework is applied to temporal image pairs and the results of combining temporal information are analyzed and discussed

NON-INVASIVE IMAGE ENHANCEMENT OF COLOUR RETINAL FUNDUS IMAGES FOR A COMPUTERISED DIABETIC RETINOPATHY MONITORING AND GRADING SYSTEM

Diabetic Retinopathy (DR) is a sight threatening complication due to diabetes mellitus affecting the retina. The pathologies of DR can be monitored by analysing colour fundus images. However, the low and varied contrast between retinal vessels and the background in colour fundus images remains an impediment to visual analysis in particular in analysing tiny retinal vessels and capillary networks. To circumvent this problem, fundus fluorescein angiography (FF A) that improves the image contrast is used. Unfortunately, it is an invasive procedure (injection of contrast dyes) that leads to other physiological problems and in the worst case may cause death. The objective of this research is to develop a non-invasive digital Image enhancement scheme that can overcome the problem of the varied and low contrast colour fundus images in order that the contrast produced is comparable to the invasive fluorescein method, and without introducing noise or artefacts. The developed image enhancement algorithm (called RETICA) is incorporated into a newly developed computerised DR system (called RETINO) that is capable to monitor and grade DR severity using colour fundus images. RETINO grades DR severity into five stages, namely No DR, Mild Non Proliferative DR (NPDR), Moderate NPDR, Severe NPDR and Proliferative DR (PDR) by enhancing the quality of digital colour fundus image using RETICA in the macular region and analysing the enlargement of the foveal avascular zone (F AZ), a region devoid of retinal vessels in the macular region. The importance of this research is to improve image quality in order to increase the accuracy, sensitivity and specificity of DR diagnosis, and to enable DR grading through either direct observation or computer assisted diagnosis system