Multiscale Cross-Approximate Entropy Analysis as a Measurement of Complexity between ECG R-R Interval and PPG Pulse Amplitude Series among the Normal and Diabetic Subjects

Physiological signals often show complex fluctuation (CF) under the dual influence of temporal and spatial scales, and CF can be used to assess the health of physiologic systems in the human body. This study applied multiscale cross-approximate entropy (MC-ApEn) to quantify the complex fluctuation between R-R intervals series and photoplethysmography amplitude series. All subjects were then divided into the following two groups: healthy upper middle-aged subjects (Group 1, age range: 41–80 years, n=27) and upper middle-aged subjects with type 2 diabetes (Group 2, age range: 41–80 years, n=24). There are significant differences of heart rate variability, LHR, between Groups 1 and 2 (1.94±1.21 versus 1.32±1.00, P=0.031). Results demonstrated differences in sum of large scale MC-ApEn (MC-ApEnLS) (5.32±0.50 versus 4.74±0.78, P=0.003). This parameter has a good agreement with pulse-pulse interval and pulse amplitude ratio (PAR), a simplified assessment for baroreflex activity. In conclusion, this study employed the MC-ApEn method, integrating multiple temporal and spatial scales, to quantify the complex interaction between the two physical signals. The MC-ApEnLS parameter could accurately reflect disease process in diabetics and might be another way for assessing the autonomic nerve function

Detection and Classification of Diabetic Retinopathy Pathologies in Fundus Images

Diabetic Retinopathy (DR) is a disease that affects up to 80% of diabetics around the world. It is the second greatest cause of blindness in the Western world, and one of the leading causes of blindness in the U.S. Many studies have demonstrated that early treatment can reduce the number of sight-threatening DR cases, mitigating the medical and economic impact of the disease. Accurate, early detection of eye disease is important because of its potential to reduce rates of blindness worldwide. Retinal photography for DR has been promoted for decades for its utility in both disease screening and clinical research studies. In recent years, several research centers have presented systems to detect pathology in retinal images. However, these approaches apply specialized algorithms to detect specific types of lesion in the retina. In order to detect multiple lesions, these systems generally implement multiple algorithms. Furthermore, some of these studies evaluate their algorithms on a single dataset, thus avoiding potential problems associated with the differences in fundus imaging devices, such as camera resolution. These methodologies primarily employ bottom-up approaches, in which the accurate segmentation of all the lesions in the retina is the basis for correct determination. A disadvantage of bottom-up approaches is that they rely on the accurate segmentation of all lesions in order to measure performance. On the other hand, top-down approaches do not depend on the segmentation of specific lesions. Thus, top-down methods can potentially detect abnormalities not explicitly used in their training phase. A disadvantage of these methods is that they cannot identify specific pathologies and require large datasets to build their training models. In this dissertation, I merged the advantages of the top-down and bottom-up approaches to detect DR with high accuracy. First, I developed an algorithm based on a top-down approach to detect abnormalities in the retina due to DR. By doing so, I was able to evaluate DR pathologies other than microaneurysms and exudates, which are the main focus of most current approaches. In addition, I demonstrated good generalization capacity of this algorithm by applying it to other eye diseases, such as age-related macular degeneration. Due to the fact that high accuracy is required for sight-threatening conditions, I developed two bottom-up approaches, since it has been proven that bottom-up approaches produce more accurate results than top-down approaches for particular structures. Consequently, I developed an algorithm to detect exudates in the macula. The presence of this pathology is considered to be a surrogate for clinical significant macular edema (CSME), a sight-threatening condition of DR. The analysis of the optic disc is usually not taken into account in DR screening systems. However, there is a pathology called neovascularization that is present in advanced stages of DR, making its detection of crucial clinical importance. In order to address this problem, I developed an algorithm to detect neovascularization in the optic disc. These algorithms are based on amplitude-modulation and frequency-modulation (AM-FM) representations, morphological image processing methods, and classification algorithms. The methods were tested on a diverse set of large databases and are considered to be the state-of the art in this field

Point-of-Care Detection Devices for Healthcare

With recent technological advances in multiple research fields such as materials science, micro-/nano-technology, cellular and molecular biology, bioengineering and the environment, much attention is shifting toward the development of new detection tools that not only address needs for high sensitivity and specificity but fulfil economic, environmental, and rapid point-of-care needs for groups and individuals with constrained resources and, possibly, limited training. Miniaturized fluidics-based platforms that precisely manipulate tiny body fluid volumes can be used for medical, healthcare or even environmental (e.g., heavy metal detection) diagnosis in a rapid and accurate manner. These new detection technologies are potentially applicable to different healthcare or environmental issues, since they are disposable, inexpensive, portable, and easy to use for the detection of human diseases or environmental issues—especially when they are manufactured based on low-cost materials, such as paper. The topics in this book (original and review articles) would cover point-of-care detection devices, microfluidic or paper-based detection devices, new materials for making detection devices, and others

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

Automated detection of proliferative diabetic retinopathy from retinal images

Diabetic retinopathy (DR) is a retinal vascular disease associated with diabetes and it is one of the most common causes of blindness worldwide. Diabetic patients regularly attend retinal screening in which digital retinal images are captured. These images undergo thorough analysis by trained individuals, which can be a very time consuming and costly task due to the large diabetic population. Therefore, this is a field that would greatly benefit from the introduction of automated detection systems. This project aims to automatically detect proliferative diabetic retinopathy (PDR), which is the most advanced stage of the disease and poses a high risk of severe visual impairment. The hallmark of PDR is neovascularisation, the growth of abnormal new vessels. Their tortuous, convoluted and obscure appearance can make them difficult to detect. In this thesis, we present a methodology based on the novel approach of creating two different segmented vessel maps. Segmentation methods include a standard line operator approach and a novel modified line operator approach. The former targets the accurate segmentation of new vessels and the latter targets the reduction of false responses to non-vessel edges. Both generated binary vessel maps hold vital information which is processed separately using a dual classification framework. Features are measured from each binary vessel map to produce two separate feature sets. Independent classification is performed for each feature set using a support vector machine (SVM) classifier. The system then combines these individual classification outcomes to produce a final decision. The proposed methodology, using a dataset of 60 images, achieves a sensitivity of 100.00% and a specificity of 92.50% on a per image basis and a sensitivity of 87.93% and a specificity of 94.40% on a per patch basis. The thesis also presents an investigation into the search for the most suitable features for the classification of PDR. This entails the expansion of the feature vector, followed by feature selection using a genetic algorithm based approach. This provides an improvement in results, which now stand at a sensitivity and specificity 3 of 100.00% and 97.50% respectively on a per image basis and 91.38% and 96.00% respectively on a per patch basis. A final extension to the project sees the framework of dual classification further explored, by comparing the results of dual SVM classification with dual ensemble classification. The results of the dual ensemble approach are deemed inferior, achieving a sensitivity and specificity of 100.00% and 95.00% respectively on a per image basis and 81.03% and 95.20% respectively on a per patch basis

Non-communicable Diseases, Big Data and Artificial Intelligence

This reprint includes 15 articles in the field of non-communicable Diseases, big data, and artificial intelligence, overviewing the most recent advances in the field of AI and their application potential in 3P medicine

Evaluation of the potentials for optical coherence tomography (OCT) to detect early signs of retinal neurodegeneration

Among neuroretinal degenerations, glaucoma and age-related macular degeneration (AMD) have become the most frequent reasons for irreversible blindness globally. Among the causes of the elderly and senile dementia, Alzheimer’s disease (AD) has the leading position, the early ocular symptoms of which can potentially be a prognostic factor. The aim of this thesis was the early in vivo ligand-free detection of degenerative changes in the inner and outer retinal layers, which was possible using high-resolution optical coherence tomography (OCT) with the machine learning (ML) algorithms: support vector machine (SVM) and principal component analysis (PCA). Prior to the application of SVM and PCA for the classification of human OCT images, evaluation of the classifiers was performed in the classification of optical phantoms, the accuracy of which was in the range of 82-100%. This was the first attempt to measure the textural properties of various polystyrene and silica beads optical phantoms. To identify optical changes that characterise early apoptosis, OCT imaging of axotomised retinal ganglion cells (RGCs) in ex vivo retinal murine explants was performed. Substantial optical alterations in RGC dendrites in the early stages of apoptosis (up to 2 hours) were detected. ML algorithms correctly classified the retinal texture of the inner plexiform layer (IPL) of transgenic AD mice in all cases, indicating the potential for further investigation in in vivo animal and human studies. Not only the optical signature but also the transparency of the dissected murine retinal explants was investigated. Moreover, ML classification of 3xTg mice IPL layer was studied in terms of optical changes due to the RGD dendritic atrophy. ML classifiers’ accuracy in the detection of early and neovascular AMD was 93-100% for the texture of retinal pigment epithelium, 69-67% for the outer nuclear layer, 70% for the inner segment and 60-90% for the outer segment of photoreceptors. Classification of AMD stages and comparison with the age-matched healthy controls was carried out in the outer retina and RPE. Grey-level co-occurrence, run-length matrices, local binary patterns features were extracted from the IPL of the macula to classify glaucoma OCT images. The accuracy of linear and non-linear SVMs, linear and quadratic discriminant analyses, decision tree and logistic regression was between 55-70%. Based on the classifiers’ precision, recall and F1-score, Gaussian SVM outperformed other ML techniques. In this study, the observation of early glaucomatous subtle optical changes of human IPL was conducted. Also, the significance of various supervised ML algorithms was investigated. Understanding the optical signature of cumulative inherent speckle of OCT scans arising from apoptotic retinal ganglion cells and photoreceptors may provide vital information for the prevention of retinal neurodegeneration