No-search focus prediction at the single cell level in digital holographic imaging with deep convolutional neural network

Digital propagation of an off-axis hologram can provide the quantitative phase-contrast image if the exact distance between the sensor plane (such as CCD) and the reconstruction plane is correctly provided. In this paper, we present a deep-learning convolutional neural network with a regression layer as the top layer to estimate the best reconstruction distance. The experimental results obtained using microsphere beads and red blood cells show that the proposed method can accurately predict the propagation distance from a filtered hologram. The result is compared with the conventional automatic focus-evaluation function. Additionally, our approach can be utilized at the single-cell level, which is useful for cell-to-cell depth measurement and cell adherent studies. © 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.1

Role of deep learning techniques in non-invasive diagnosis of human diseases.

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than ever due to the increase in medical data being acquired, the presence of novel modalities being developed and the complexity of medical data. In all of these scenarios, machine learning can come up with new tools for interpreting the complex datasets that confront clinicians. Much of the excitement for the application of machine learning to biomedical research comes from the development of deep learning which is modeled after computation in the brain. Deep learning can help in attaining insights that would be impossible to obtain through manual analysis. Deep learning algorithms and in particular convolutional neural networks are different from traditional machine learning approaches. Deep learning algorithms are known by their ability to learn complex representations to enhance pattern recognition from raw data. On the other hand, traditional machine learning requires human engineering and domain expertise to design feature extractors and structure data. With increasing demands upon current radiologists, there are growing needs for automating the diagnosis. This is a concern that deep learning is able to address. In this dissertation, we present four different successful applications of deep learning for diseases diagnosis. All the work presented in the dissertation utilizes medical images. In the first application, we introduce a deep-learning based computer-aided diagnostic system for the early detection of acute renal transplant rejection. The system is based on the fusion of both imaging markers (apparent diffusion coefficients derived from diffusion-weighted magnetic resonance imaging) and clinical biomarkers (creatinine clearance and serum plasma creatinine). The fused data is then used as an input to train and test a convolutional neural network based classifier. The proposed system is tested on scans collected from 56 subjects from geographically diverse populations and different scanner types/image collection protocols. The overall accuracy of the proposed system is 92.9% with 93.3% sensitivity and 92.3% specificity in distinguishing non-rejected kidney transplants from rejected ones. In the second application, we propose a novel deep learning approach for the automated segmentation and quantification of the LV from cardiac cine MR images. We aimed at achieving lower errors for the estimated heart parameters compared to the previous studies by proposing a novel deep learning segmentation method. Using fully convolutional neural networks, we proposed novel methods for the extraction of a region of interest that contains the left ventricle, and the segmentation of the left ventricle. Following myocardial segmentation, functional and mass parameters of the left ventricle are estimated. Automated Cardiac Diagnosis Challenge dataset was used to validate our framework, which gave better segmentation, accurate estimation of cardiac parameters, and produced less error compared to other methods applied on the same dataset. Furthermore, we showed that our segmentation approach generalizes well across different datasets by testing its performance on a locally acquired dataset. In the third application, we propose a novel deep learning approach for automated quantification of strain from cardiac cine MR images of mice. For strain analysis, we developed a Laplace-based approach to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. In the fourth application, we demonstrate how a deep learning approach can be utilized for the automated classification of kidney histopathological images. Our approach can classify four classes: the fat, the parenchyma, the clear cell renal cell carcinoma, and the unusual cancer which has been discovered recently, called clear cell papillary renal cell carcinoma. Our framework consists of three convolutional neural networks and the whole-slide kidney images were divided into patches with three different sizes to be inputted to the networks. Our approach can provide patch-wise and pixel-wise classification. Our approach classified the four classes accurately and surpassed other state-of-the-art methods such as ResNet (pixel accuracy: 0.89 Resnet18, 0.93 proposed). In conclusion, the results of our proposed systems demonstrate the potential of deep learning for the efficient, reproducible, fast, and affordable disease diagnosis

Digital Twin of Cardiovascular Systems

Patient specific modelling using numerical methods is widely used in understanding diseases and disorders. It produces medical analysis based on the current state of patient’s health. Concurrently, as a parallel development, emerging data driven Artificial Intelligence (AI) has accelerated patient care. It provides medical analysis using algorithms that rely upon knowledge from larger human population data. AI systems are also known to have the capacity to provide a prognosis with overallaccuracy levels that are better than those provided by trained professionals. When these two independent and robust methods are combined, the concept of human digital twins arise. A Digital Twin is a digital replica of any given system or process. They combine knowledge from general data with subject oriented knowledge for past, current and future analyses and predictions. Assumptions made during numerical modelling are compensated using knowledge from general data. For humans, they can provide an accurate current diagnosis as well as possible future outcomes. This allows forprecautions to be taken so as to avoid further degradation of patient’s health.In this thesis, we explore primary forms of human digital twins for the cardiovascular system, that are capable of replicating various aspects of the cardiovascular system using different types of data. Since different types of medical data are available, such as images, videos and waveforms, and the kinds of analysis required may be offline or online in nature, digital twin systems should be uniquely designed to capture each type of data for different kinds of analysis. Therefore, passive, active and semi-active digital twins, as the three primary forms of digital twins, for different kinds of applications are proposed in this thesis. By the virtue of applications and the kind of data involved ineach of these applications, the performance and importance of human digital twins for the cardiovascular system are demonstrated. The idea behind these twins is to allow for the application of the digital twin concept for online analysis, offline analysis or a combination of the two in healthcare. In active digital twins active data, such as signals, is analysed online in real-time; in semi-active digital twin some of the components being analysed are active but the analysis itself is carried out offline; and finally, passive digital twins perform offline analysis of data that involves no active component.For passive digital twin, an automatic workflow to calculate Fractional Flow Reserve (FFR) is proposed and tested on a cohort of 25 patients with acceptable results. For semi-active digital twin, detection of carotid stenosis and its severity using face videos is proposed and tested with satisfactory results from one carotid stenosis patient and a small cohort of healthy adults. Finally, for the active digital twin, an enabling model is proposed using inverse analysis and its application in the detection of Abdominal Aortic Aneurysm (AAA) and its severity, with the help of a virtual patient database. This enabling model detected artificially generated AAA with an accuracy as high as 99.91% and classified its severity with acceptable accuracy of 97.79%. Further, for active digital twin, a truly active model is proposed for continuous cardiovascular state monitoring. It is tested on a small cohort of five patients from a publicly available database for three 10-minute periods, wherein this model satisfactorily replicated and forecasted patients’ cardiovascular state. In addition to the three forms of human digital twins for the cardiovascular system, an additional work on patient prioritisation in pneumonia patients for ITU care using data-driven digital twin is also proposed. The severity indices calculated by these models are assessed using the standard benchmark of Area Under Receiving Operating Characteristic Curve (AUROC). The results indicate that using these models, the ITU and mechanical ventilation can be prioritised correctly to an AUROC value as high as 0.89

Echo Particle Image/Tracking Velocimetry: Technical Development and In Vivo Applications in Cardiovascular and Cerebrovascular Flows

Contrast-enhanced ultrasound (CEUS) imaging utilizes intravascular echogenic microbubbles (1-5μm in diameter) to visualize the blood flow in various organs. In this dissertation, we develop and implement techniques for analyzing the motions of microbubbles to quantify cardiovascular and cerebrovascular flows. Obtaining accurate bubble center locations from noisy CEUS images is a primary challenge. Since the bubble trace is typically modeled as a point scatter convolved with a point spread function (PSF), techniques including blind deconvolution, supervised, and self-supervised learning are introduced and calibrated for identifying the PSF and locating the bubble center. The enhanced CEUS images enable echo particle image velocimetry (echo-PIV) for characterizing 2D cardiovascular flows, and the global-optimized Kalman filter-based echo particle tracking velocimetry (echo-PTV) for determining bubble trajectories which are subsequently used for mapping the cerebral and ocular microcirculation at a spatial resolution of 20μm. These techniques are applied to two applications. First, echo-PIV is used for monitoring the aortic root flow in an adult pig undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO), a life support technology whose parameters can be optimized based on the aortic root hemodynamics. Phase-averaged and instantaneous flow fields show that, for the pig with severe myocardial ischemia, the cardiac ejection velocity, velocity-time integral, and mean arterial pressure (MAP) reach their peak at an ECMO flow rate of 3.0L/min, indicating an optimal flow rate that provides adequate support. Second, we investigate non-invasive methods for estimating intracranial pressure (ICP), a critical parameter for hydrocephalus patients that cannot be invasively measured safely. Echo-PTV is used to map cerebral and ocular microcirculation of pediatric hydrocephalus porcine models for inferring ICP. Results show that accounting for pulse pressure, highly correlated relationships between ICP and cortical microcirculation density are obtained with correlation coefficients beyond 0.85. For cerebral ischemia, nondimensionalized cortical micro-perfusion decreases by an order of magnitude when the ICP exceeds 50% of MAP. Moreover, retinal microcirculation also shows a highly correlated relationship with ICP when accounting for pulse pressure. These findings suggest that CEUS-based microcirculation measurement is a plausible noninvasive method for evaluating the ICP and detecting brain ischemia

Learning Better Clinical Risk Models.

Risk models are used to estimate a patient’s risk of suffering particular outcomes throughout clinical practice. These models are important for matching patients to the appropriate level of treatment, for effective allocation of resources, and for fairly evaluating the performance of healthcare providers. The application and development of methods from the field of machine learning has the potential to improve patient outcomes and reduce healthcare spending with more accurate estimates of patient risk. This dissertation addresses several limitations of currently used clinical risk models, through the identification of novel risk factors and through the training of more effective models. As wearable monitors become more effective and less costly, the previously untapped predictive information in a patient’s physiology over time has the potential to greatly improve clinical practice. However translating these technological advances into real-world clinical impacts will require computational methods to identify high-risk structure in the data. This dissertation presents several approaches to learning risk factors from physiological recordings, through the discovery of latent states using topic models, and through the identification of predictive features using convolutional neural networks. We evaluate these approaches on patients from a large clinical trial and find that these methods not only outperform prior approaches to leveraging heart rate for cardiac risk stratification, but that they improve overall prediction of cardiac death when considered alongside standard clinical risk factors. We also demonstrate the utility of this work for learning a richer description of sleep recordings. Additionally, we consider the development of risk models in the presence of missing data, which is ubiquitous in real-world medical settings. We present a novel method for jointly learning risk and imputation models in the presence of missing data, and find significant improvements relative to standard approaches when evaluated on a large national registry of trauma patients.PhDComputer Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113326/1/alexve_1.pd

Personalized data analytics for internet-of-things-based health monitoring

The Internet-of-Things (IoT) has great potential to fundamentally alter the delivery of modern healthcare, enabling healthcare solutions outside the limits of conventional clinical settings. It can offer ubiquitous monitoring to at-risk population groups and allow diagnostic care, preventive care, and early intervention in everyday life. These services can have profound impacts on many aspects of health and well-being. However, this field is still at an infancy stage, and the use of IoT-based systems in real-world healthcare applications introduces new challenges. Healthcare applications necessitate satisfactory quality attributes such as reliability and accuracy due to their mission-critical nature, while at the same time, IoT-based systems mostly operate over constrained shared sensing, communication, and computing resources. There is a need to investigate this synergy between the IoT technologies and healthcare applications from a user-centered perspective. Such a study should examine the role and requirements of IoT-based systems in real-world health monitoring applications. Moreover, conventional computing architecture and data analytic approaches introduced for IoT systems are insufficient when used to target health and well-being purposes, as they are unable to overcome the limitations of IoT systems while fulfilling the needs of healthcare applications. This thesis aims to address these issues by proposing an intelligent use of data and computing resources in IoT-based systems, which can lead to a high-level performance and satisfy the stringent requirements. For this purpose, this thesis first delves into the state-of-the-art IoT-enabled healthcare systems proposed for in-home and in-hospital monitoring. The findings are analyzed and categorized into different domains from a user-centered perspective. The selection of home-based applications is focused on the monitoring of the elderly who require more remote care and support compared to other groups of people. In contrast, the hospital-based applications include the role of existing IoT in patient monitoring and hospital management systems. Then, the objectives and requirements of each domain are investigated and discussed. This thesis proposes personalized data analytic approaches to fulfill the requirements and meet the objectives of IoT-based healthcare systems. In this regard, a new computing architecture is introduced, using computing resources in different layers of IoT to provide a high level of availability and accuracy for healthcare services. This architecture allows the hierarchical partitioning of machine learning algorithms in these systems and enables an adaptive system behavior with respect to the user's condition. In addition, personalized data fusion and modeling techniques are presented, exploiting multivariate and longitudinal data in IoT systems to improve the quality attributes of healthcare applications. First, a real-time missing data resilient decision-making technique is proposed for health monitoring systems. The technique tailors various data resources in IoT systems to accurately estimate health decisions despite missing data in the monitoring. Second, a personalized model is presented, enabling variations and event detection in long-term monitoring systems. The model evaluates the sleep quality of users according to their own historical data. Finally, the performance of the computing architecture and the techniques are evaluated in this thesis using two case studies. The first case study consists of real-time arrhythmia detection in electrocardiography signals collected from patients suffering from cardiovascular diseases. The second case study is continuous maternal health monitoring during pregnancy and postpartum. It includes a real human subject trial carried out with twenty pregnant women for seven months

Advances in transfer learning methods based on computational intelligence

Traditional machine learning and data mining have made tremendous progress in many knowledge-based areas, such as clustering, classification, and regression. However, the primary assumption in all of these areas is that the training and testing data should be in the same domain and have the same distribution. This assumption is difficult to achieve in real-world applications due to the limited availability of labeled data. Associated data in different domains can be used to expand the availability of prior knowledge about future target data. In recent years, transfer learning has been used to address such cross-domain learning problems by using information from data in a related domain and transferring that data to the target task. The transfer learning methodology is utilized in this work with unsupervised and supervised learning methods. For unsupervised learning, a novel transfer-learning possibilistic c-means (TLPCM) algorithm is proposed to handle the PCM clustering problem in a domain that has insufficient data. Moreover, TLPCM overcomes the problem of differing numbers of clusters between the source and target domains. The proposed algorithm employs the historical cluster centers of the source data as a reference to guide the clustering of the target data. The experimental studies presented here were thoroughly evaluated, and they demonstrate the advantages of TLPCM in both synthetic and real-world transfer datasets. For supervised learning, a transfer learning (TL) technique is used to pre-train a CNN model on posture data and then fine-tune it on the sleep stage data. We used a ballistocardiography (BCG) bed sensor to collect both posture and sleep stage data to provide a non-invasive, in-home monitoring system that tracks changes in the subjects' health over time. The quality of sleep has a significant impact on health and life. This study adopts a hierarchical and none-hierarchical classification structure to develop an automatic sleep stage classification system using ballistocardiogram (BCG) signals. A leave-one-subject-out cross-validation (LOSO-CV) procedure is used for testing classification performance in most of the experiments. Convolutional Neural Networks (CNNs), Long Short-Term Memory (LSTM), and Deep Neural Networks DNNs are complementary in their modeling capabilities, while CNNs have the advantage of reducing frequency variations, LSTMs are good at temporal modeling. Polysomnography (PSG) data from a sleep lab was used as the ground truth for sleep stages, with the emphasis on three sleep stages, specifically, awake, rapid eye movement (REM), and non-REM sleep (NREM). Moreover, a transfer learning approach is employed with supervised learning to address the cross-resident training problem to predict early illness. We validate our method by conducting a retrospective study on three residents from TigerPlace, a retirement community in Columbia, MO, where apartments are fitted with wireless networks of motion and bed sensors. Predicting the early signs of illness in older adults by using a continuous, unobtrusive nursing home monitoring system has been shown to increase the quality of life and decrease care costs. Illness prediction is based on sensor data and uses algorithms such as support vector machine (SVM) and k-nearest neighbors (kNN). One of the most significant challenges related to the development of prediction algorithms for sensor networks is the use of knowledge from previous residents to predict new ones' behaviors. Each day, the presence or absence of illness was manually evaluated using nursing visit reports from a homegrown electronic medical record (EMR) system. In this work, the transfer learning SVM approach outperformed three other methods, i.e., regular SVM, one-class SVM, and one-class kNN.Includes bibliographical references (pages 114-127)