Identifying evolving multivariate dynamics in individual and cohort time series, with application to physiological control systems

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 117-125).Physiological control systems involve multiple interacting variables operating in feedback loops that enhance an organism's ability to self-regulate and respond to internal and external disturbances. The resulting multivariate time-series often exhibit rich dynamical patterns, which are altered under pathological conditions. However, model identification for physiological systems is complicated by measurement artifacts and changes between operating regimes. The overall aim of this thesis is to develop and validate computational tools for identification and analysis of structured multivariate models of physiological dynamics in individual and cohort time-series. We first address the identification and stability of the respiratory chemoreflex system, which is key to the pathogenesis of sleep-induced periodic breathing and apnea. Using data from both an animal model of periodic breathing, as well as human recordings from clinical sleep studies, we demonstrate that model-based analysis of the interactions involved in spontaneous breathing can characterize the dynamics of the respiratory control system, and provide a useful tool for quantifying the contribution of various dynamic factors to ventilatory instability. The techniques have suggested novel approaches to titration of combination therapies, and clinical evaluations are now underway. We then study shared multivariate dynamics in physiological cohort time-series, assuming that the time-series are generated by switching among a finite collection of physiologically constrained dynamical models. Patients whose time-series exhibit similar dynamics may be grouped for monitoring and outcome prediction. We develop a novel parallelizable machine-learning algorithm for outcome-discriminative identification of the switching dynamics, using a probabilistic dynamic Bayesian network to initialize a deterministic neural network classifier. In validation studies involving simulated data and human laboratory recordings, the new technique significantly outperforms the standard expectation-maximization approach for identification of switching dynamics. In a clinical application, we show the prognostic value of assessing evolving dynamics in blood pressure time-series to predict mortality in a cohort of intensive care unit patients. A better understanding of the dynamics of physiological systems in both health and disease may enable clinicians to direct therapeutic interventions targeted to specific underlying mechanisms. The techniques developed in this thesis are general, and can be extended to other domains involving multi-dimensional cohort time-series.by Shamim Nemati.Ph.D

Learning Tasks for Multitask Learning: Heterogenous Patient Populations in the ICU

Machine learning approaches have been effective in predicting adverse outcomes in different clinical settings. These models are often developed and evaluated on datasets with heterogeneous patient populations. However, good predictive performance on the aggregate population does not imply good performance for specific groups. In this work, we present a two-step framework to 1) learn relevant patient subgroups, and 2) predict an outcome for separate patient populations in a multi-task framework, where each population is a separate task. We demonstrate how to discover relevant groups in an unsupervised way with a sequence-to-sequence autoencoder. We show that using these groups in a multi-task framework leads to better predictive performance of in-hospital mortality both across groups and overall. We also highlight the need for more granular evaluation of performance when dealing with heterogeneous populations.Comment: KDD 201

Combining mobile-health (mHealth) and artificial intelligence (AI) methods to avoid suicide attempts: the Smartcrises study protocol

The screening of digital footprint for clinical purposes relies on the capacity of wearable technologies to collect data and extract relevant information’s for patient management. Artificial intelligence (AI) techniques allow processing of real-time observational information and continuously learning from data to build understanding. We designed a system able to get clinical sense from digital footprints based on the smartphone’s native sensors and advanced machine learning and signal processing techniques in order to identify suicide risk. Method/design: The Smartcrisis study is a cross-national comparative study. The study goal is to determine the relationship between suicide risk and changes in sleep quality and disturbed appetite. Outpatients from the Hospital Fundación Jiménez Díaz Psychiatry Department (Madrid, Spain) and the University Hospital of Nimes (France) will be proposed to participate to the study. Two smartphone applications and a wearable armband will be used to capture the data. In the intervention group, a smartphone application (MEmind) will allow for the ecological momentary assessment (EMA) data capture related with sleep, appetite and suicide ideations. Discussion: Some concerns regarding data security might be raised. Our system complies with the highest level of security regarding patients’ data. Several important ethical considerations related to EMA method must also be considered. EMA methods entails a non-negligible time commitment on behalf of the participants. EMA rely on daily, or sometimes more frequent, Smartphone notifications. Furthermore, recording participants’ daily experiences in a continuous manner is an integral part of EMA. This approach may be significantly more than asking a participant to complete a retrospective questionnaire but also more accurate in terms of symptoms monitoring. Overall, we believe that Smartcrises could participate to a paradigm shift from the traditional identification of risks factors to personalized prevention strategies tailored to characteristics for each patientThis study was partly funded by Fundación Jiménez Díaz Hospital, Instituto de Salud Carlos III (PI16/01852), Delegación del Gobierno para el Plan Nacional de Drogas (20151073), American Foundation for Suicide Prevention (AFSP) (LSRG-1-005-16), the Madrid Regional Government (B2017/BMD-3740 AGES-CM 2CM; Y2018/TCS-4705 PRACTICO-CM) and Structural Funds of the European Union. MINECO/FEDER (‘ADVENTURE’, id. TEC2015–69868-C2–1-R) and MCIU Explora Grant ‘aMBITION’ (id. TEC2017–92552-EXP), the French Embassy in Madrid, Spain, The foundation de l’avenir, and the Fondation de France. The work of D. Ramírez and A. Artés-Rodríguez has been partly supported by Ministerio de Economía of Spain under projects: OTOSIS (TEC2013–41718-R), AID (TEC2014–62194-EXP) and the COMONSENS Network (TEC2015–69648-REDC), by the Ministerio de Economía of Spain jointly with the European Commission (ERDF) under projects ADVENTURE (TEC2015– 69868-C2–1-R) and CAIMAN (TEC2017–86921-C2–2-R), and by the Comunidad de Madrid under project CASI-CAM-CM (S2013/ICE-2845). The work of P. Moreno-Muñoz has been supported by FPI grant BES-2016-07762

Machine learning in critical care: state-of-the-art and a sepsis case study

Background: Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This challenge entails the daunting task of extracting usable knowledge from these data using algorithmic methods. In the medical context this may for instance realized through the design of medical decision support systems for diagnosis, prognosis and patient management. The intensive care unit (ICU), and by extension the whole area of critical care, is becoming one of the most data-driven clinical environments. Results: The increasing availability of complex and heterogeneous data at the point of patient attention in critical care environments makes the development of fresh approaches to data analysis almost compulsory. Computational Intelligence (CI) and Machine Learning (ML) methods can provide such approaches and have already shown their usefulness in addressing problems in this context. The current study has a dual goal: it is first a review of the state-of-the-art on the use and application of such methods in the field of critical care. Such review is presented from the viewpoint of the different subfields of critical care, but also from the viewpoint of the different available ML and CI techniques. The second goal is presenting a collection of results that illustrate the breath of possibilities opened by ML and CI methods using a single problem, the investigation of septic shock at the ICU. Conclusion: We have presented a structured state-of-the-art that illustrates the broad-ranging ways in which ML and CI methods can make a difference in problems affecting the manifold areas of critical care. The potential of ML and CI has been illustrated in detail through an example concerning the sepsis pathology. The new definitions of sepsis and the relevance of using the systemic inflammatory response syndrome (SIRS) in its diagnosis have been considered. Conditional independence models have been used to address this problem, showing that SIRS depends on both organ dysfunction measured through the Sequential Organ Failure (SOFA) score and the ICU outcome, thus concluding that SIRS should still be considered in the study of the pathophysiology of Sepsis. Current assessment of the risk of dead at the ICU lacks specificity. ML and CI techniques are shown to improve the assessment using both indicators already in place and other clinical variables that are routinely measured. Kernel methods in particular are shown to provide the best performance balance while being amenable to representation through graphical models, which increases their interpretability and, with it, their likelihood to be accepted in medical practice.Peer ReviewedPostprint (published version

Generating synthetic mixed-type longitudinal electronic health records for artificial intelligent applications

The recent availability of electronic health records (EHRs) have provided enormous opportunities to develop artificial intelligence (AI) algorithms. However, patient privacy has become a major concern that limits data sharing across hospital settings and subsequently hinders the advances in AI. Synthetic data, which benefits from the development and proliferation of generative models, has served as a promising substitute for real patient EHR data. However, the current generative models are limited as they only generate single type of clinical data for a synthetic patient, i.e., either continuous-valued or discrete-valued. To mimic the nature of clinical decision-making which encompasses various data types/sources, in this study, we propose a generative adversarial network (GAN) entitled EHR-M-GAN that simultaneously synthesizes mixed-type timeseries EHR data. EHR-M-GAN is capable of capturing the multidimensional, heterogeneous, and correlated temporal dynamics in patient trajectories. We have validated EHR-M-GAN on three publicly-available intensive care unit databases with records from a total of 141,488 unique patients, and performed privacy risk evaluation of the proposed model. EHR-M-GAN has demonstrated its superiority over state-of-the-art benchmarks for synthesizing clinical timeseries with high fidelity, while addressing the limitations regarding data types and dimensionality in the current generative models. Notably, prediction models for outcomes of intensive care performed significantly better when training data was augmented with the addition of EHR-M-GAN-generated timeseries. EHR-M-GAN may have use in developing AI algorithms in resource-limited settings, lowering the barrier for data acquisition while preserving patient privacy

A Machine Learning Approach to Monitor the Emergence of Late Intrauterine Growth Restriction

Late intrauterine growth restriction (IUGR) is a fetal pathological condition characterized by chronic hypoxia secondary to placental insufficiency, resulting in an abnormal rate of fetal growth. This pathology has been associated with increased fetal and neonatal morbidity and mortality. In standard clinical practice, late IUGR diagnosis can only be suspected in the third trimester and ultimately confirmed at birth. This study presents a radial basis function support vector machine (RBF-SVM) classification based on quantitative features extracted from fetal heart rate (FHR) signals acquired using routine cardiotocography (CTG) in a population of 160 healthy and 102 late IUGR fetuses. First, the individual performance of each time, frequency, and nonlinear feature was tested. To improve the unsatisfactory results of univariate analysis we firstly adopted a Recursive Feature Elimination approach to select the best subset of FHR-based parameters contributing to the discrimination of healthy vs. late IUGR fetuses. A fine tuning of the RBF-SVM model parameters resulted in a satisfactory classification performance in the training set (accuracy 0.93, sensitivity 0.93, specificity 0.84). Comparable results were obtained when applying the model on a totally independent testing set. This investigation supports the use of a multivariate approach for the in utero identification of late IUGR condition based on quantitative FHR features encompassing different domains. The proposed model allows describing the relationships among features beyond the traditional linear approaches, thus improving the classification performance. This framework has the potential to be proposed as a screening tool for the identification of late IUGR fetuses