Computational Intelligence Methods for Medical Image Understanding, Visualization, and Interaction

Ph.DDOCTOR OF PHILOSOPH

Intelligent Biosignal Processing in Wearable and Implantable Sensors

This reprint provides a collection of papers illustrating the state-of-the-art of smart processing of data coming from wearable, implantable or portable sensors. Each paper presents the design, databases used, methodological background, obtained results, and their interpretation for biomedical applications. Revealing examples are brain–machine interfaces for medical rehabilitation, the evaluation of sympathetic nerve activity, a novel automated diagnostic tool based on ECG data to diagnose COVID-19, machine learning-based hypertension risk assessment by means of photoplethysmography and electrocardiography signals, Parkinsonian gait assessment using machine learning tools, thorough analysis of compressive sensing of ECG signals, development of a nanotechnology application for decoding vagus-nerve activity, detection of liver dysfunction using a wearable electronic nose system, prosthetic hand control using surface electromyography, epileptic seizure detection using a CNN, and premature ventricular contraction detection using deep metric learning. Thus, this reprint presents significant clinical applications as well as valuable new research issues, providing current illustrations of this new field of research by addressing the promises, challenges, and hurdles associated with the synergy of biosignal processing and AI through 16 different pertinent studies. Covering a wide range of research and application areas, this book is an excellent resource for researchers, physicians, academics, and PhD or master students working on (bio)signal and image processing, AI, biomaterials, biomechanics, and biotechnology with applications in medicine

Delivering Reliable AI to Clinical Contexts: Addressing the Challenge of Missing Data

Clinical data are essential in the medical domain, ensuring quality of care and improving decision-making. However, their heterogeneous and incomplete nature leads to an ubiquity of data quality problems, particularly missing values. Inevitable challenges arise in delivering reliable Decision Support Systems (DSSs), as missing data yield negative effects on the learning process of Machine Learning models. The interest in developing missing value imputation strategies has been growing, in an endeavour to overcome this issue. This dissertation aimed to study missing data and their relationships with observed values, and to lateremploy that information in a technique that addresses the predicaments posed by incomplete datasets in real-world scenarios. Moreover, the concept of correlation was explored within the context of missing value imputation, a promising but rather overlooked approach in biomedical research. First, a comprehensive correlational study was performed, which considered key aspects from missing data analysis. Afterwards, the gathered knowledge was leveraged to create three novel correlation-based imputation techniques. Thesewere not only validated on datasets with a controlled and synthetic missingness, but also on real-world medical datasets. Their performance was evaluated against competing imputation methods, both traditional and state-of-the-art. The contributions of this dissertation encompass a systematic view of theoretical concepts regarding the analysis and handling of missing values. Additionally, an extensive literature review concerning missing data imputation was conducted, which comprised a comparative study of ten methods under diverse missingness conditions. The proposed techniques exhibited similar results when compared to their competitors, sometimes even superior in terms of imputation precision and classification performance, evaluated through the Mean Absolute Error and the Area Under the Receiver Operating Characteristic curve, respectively. Therefore, this dissertation corroborates the potential of correlation to improve the robustness of DSSs to missing values, and provides answers to current flaws shared by correlation-based imputation strategies in real-world medical problems.Dados clínicos são essenciais para assegurar cuidados médicos de qualidade e melhorar a tomada de decisões. Contudo, a sua natureza heterogénea e incompleta cria uma ubiquidade de problemas de qualidade, nomeadamente pela existência de valores em falta. Esta condição origina desafios inevitáveis para a disponibilização de Sistemas de Apoio à Decisão (SADs) fiáveis, já que dados em falta acarretam efeitos negativos no treino de modelos de Aprendizagem Automática. O interesse no desenvolvimento de estratégias de imputação de valores em falta tem vindo a crescer, num esforço para superar esta adversidade. Esta dissertação visou estudar o problema dos dados em falta através das relações que estes apresentam com os valores observados. Esta informação foi depois utilizada no desenvolvimento de técnicas para colmatar os problemas impostos por dados incompletos em cenários reais. Ademais, o conceito de correlação foi explorado no contexto da imputação de valores em falta, já que, apesar de promissor, tem vindo a ser negligenciado em investigação biomédica. Em primeiro lugar, foi realizado um estudo correlacional abrangente que contemplou aspetos fundamentais da análise de dados em falta. Posteriormente, o conhecimento recolhido foi aplicado na criação de três novas técnicas de imputação baseadas na correlação. Estas foram validadas não só em conjuntos de dados com incompletude controlada e sintética, mas também em conjuntos de dados médicos reais. O seu desempenho foi avaliado e comparado a métodos de imputação tanto tradicionais como de estado-de-arte. As contribuições desta dissertação passam pela sistematização de conceitos teóricos relativos à análise e tratamento de dados em falta. Adicionalmente, realizou-se uma extensa revisão da literatura referente à imputação de dados, que compreendeu um estudo comparativo de dez métodos sob diversas condições de incompletude. As técnicas propostas exibiram resultados semelhantes aos dos restantes métodos, por vezes até superiores em termos de precisão da imputação e de performance da classificação. Assim, esta dissertação corrobora o potencial da utilização da correlação na melhoria da robustez de SADs a dados em falta, e fornece respostas a algumas das atuais falhas partilhadas por estratégias de imputação baseadas em correlação quando aplicadas a casos médicos reais

Quantifying cognitive and mortality outcomes in older patients following acute illness using epidemiological and machine learning approaches

Introduction: Cognitive and functional decompensation during acute illness in older people are poorly understood. It remains unclear how delirium, an acute confusional state reflective of cognitive decompensation, is contextualised by baseline premorbid cognition and relates to long-term adverse outcomes. High-dimensional machine learning offers a novel, feasible and enticing approach for stratifying acute illness in older people, improving treatment consistency while optimising future research design. Methods: Longitudinal associations were analysed from the Delirium and Population Health Informatics Cohort (DELPHIC) study, a prospective cohort ≥70 years resident in Camden, with cognitive and functional ascertainment at baseline and 2-year follow-up, and daily assessments during incident hospitalisation. Second, using routine clinical data from UCLH, I constructed an extreme gradient-boosted trees predicting 600-day mortality for unselected acute admissions of oldest-old patients with mechanistic inferences. Third, hierarchical agglomerative clustering was performed to demonstrate structure within DELPHIC participants, with predictive implications for survival and length of stay. Results: i. Delirium is associated with increased rates of cognitive decline and mortality risk, in a dose-dependent manner, with an interaction between baseline cognition and delirium exposure. Those with highest delirium exposure but also best premorbid cognition have the “most to lose”. ii. High-dimensional multimodal machine learning models can predict mortality in oldest-old populations with 0.874 accuracy. The anterior cingulate and angular gyri, and extracranial soft tissue, are the highest contributory intracranial and extracranial features respectively. iii. Clinically useful acute illness subtypes in older people can be described using longitudinal clinical, functional, and biochemical features. Conclusions: Interactions between baseline cognition and delirium exposure during acute illness in older patients result in divergent long-term adverse outcomes. Supervised machine learning can robustly predict mortality in in oldest-old patients, producing a valuable prognostication tool using routinely collected data, ready for clinical deployment. Preliminary findings suggest possible discernible subtypes within acute illness in older people

Deep learning approaches to multimodal MRI brain age estimation

Brain ageing remains an intricate, multifaceted process, marked not just by chronological time but by a myriad of structural, functional, and microstructural changes that often lead to discrepancies between actual age and the age inferred from neuroimaging. Machine learning methods, and especially Convolutional Neural Networks (CNNs), have proven adept in capturing patterns relating to ageing induced changes in the brain. The differences between the predicted and chronological ages, referred to as brain age deltas, have emerged as useful biomarkers for exploring those factors which promote accelerated ageing or resilience, such as pathologies or lifestyle factors. However, previous studies relied overwhelmingly on structural neuroimaging for predictions, overlooking rich details inherent in other MRI modalities, such as potentially informative functional and microstructural changes. This research, utilising the extensive UK Biobank dataset, reveals that 57 different maps spanning structural, susceptibility-weighted, diffusion, and functional MRI modalities can not only predict an individual's chronological age, but also encode unique ageing-related details. Through the use of both 3D CNNs and the novel 3D Shifted Window (SWIN) Transformers, this work uncovered associations between brain age deltas and 191 different non-imaging derived phenotypes (nIDPs), offering a valuable insight into factors influencing brain ageing. Moreover, this work found that ensembling data from multiple maps results in higher prediction accuracies. After a thorough comparison of both linear and non-linear multi-modal ensembling methods, including deep fusion networks, it was found that linear methods, such as ElasticNet, generally outperform their more complex non-linear counterparts. In addition, while ensembling was found to strengthen age prediction accuracies, it was found to weaken nIDP associations in certain circumstances where ensembled maps might have opposing sensitivities to a particular nIDP, thus reinforcing the need for guided selections of the ensemble components. Finally, while both CNNs and SWINs show comparable brain age prediction precision, SWIN networks stand out for their robustness against data corruption, while also proving a degree of inherent explainability. Overall, the results presented herein demonstrate that other 3D maps and modalities, which have not been considered previously for the task of brain age prediction, encode different information about the ageing brain. This research lays the foundation for further explorations into how different factors, such as off-target drug effects, impact brain ageing. It also ushers in possibilities for enhanced clinical trial design, diagnostic approaches, and therapeutic monitoring grounded in refined brain age prediction models

Complexity-Based Measures Inform Effects of Tai Chi Training on Standing Postural Control: Cross-Sectional and Randomized Trial Studies

Background: Diminished control of standing balance, traditionally indicated by greater postural sway magnitude and speed, is associated with falls in older adults. Tai Chi (TC) is a multisystem intervention that reduces fall risk, yet its impact on sway measures vary considerably. We hypothesized that TC improves the integrated function of multiple control systems influencing balance, quantifiable by the multi-scale “complexity” of postural sway fluctuations. Objectives: To evaluate both traditional and complexity-based measures of sway to characterize the short- and potential long-term effects of TC training on postural control and the relationships between sway measures and physical function in healthy older adults. Methods: A cross-sectional comparison of standing postural sway in healthy TC-naïve and TC-expert (24.5±12 yrs experience) adults. TC-naïve participants then completed a 6-month, two-arm, wait-list randomized clinical trial of TC training. Postural sway was assessed before and after the training during standing on a force-plate with eyes-open (EO) and eyes-closed (EC). Anterior-posterior (AP) and medio-lateral (ML) sway speed, magnitude, and complexity (quantified by multiscale entropy) were calculated. Single-legged standing time and Timed-Up–and-Go tests characterized physical function. Results: At baseline, compared to TC-naïve adults (n = 60, age 64.5±7.5 yrs), TC-experts (n = 27, age 62.8±7.5 yrs) exhibited greater complexity of sway in the AP EC (P = 0.023), ML EO (P<0.001), and ML EC (P<0.001) conditions. Traditional measures of sway speed and magnitude were not significantly lower among TC-experts. Intention-to-treat analyses indicated no significant effects of short-term TC training; however, increases in AP EC and ML EC complexity amongst those randomized to TC were positively correlated with practice hours (P = 0.044, P = 0.018). Long- and short-term TC training were positively associated with physical function. Conclusion: Multiscale entropy offers a complementary approach to traditional COP measures for characterizing sway during quiet standing, and may be more sensitive to the effects of TC in healthy adults. Trial Registration ClinicalTrials.gov NCT0134036

Utilizing Temporal Information in The EHR for Developing a Novel Continuous Prediction Model

Type 2 diabetes mellitus (T2DM) is a nation-wide prevalent chronic condition, which includes direct and indirect healthcare costs. T2DM, however, is a preventable chronic condition based on previous clinical research. Many prediction models were based on the risk factors identified by clinical trials. One of the major tasks of the T2DM prediction models is to estimate the risks for further testing by HbA1c or fasting plasma glucose to determine whether the patient has or does not have T2DM because nation-wide screening is not cost-effective. Those models had substantial limitations on data quality, such as missing values. In this dissertation, I tested the conventional models which were based on the most widely used risk factors to predict the possibility of developing T2DM. The AUC was an average of 0.5, which implies the conventional model cannot be used to screen for T2DM risks. Based on this result, I further implemented three types of temporal representations, including non-temporal representation, interval-temporal representation, and continuous-temporal representation for building the T2DM prediction model. According to the results, continuous-temporal representation had the best performance. Continuous-temporal representation was based on deep learning methods. The result implied that the deep learning method could overcome the data quality issue and could achieve better performance. This dissertation also contributes to a continuous risk output model based on the seq2seq model. This model can generate a monotonic increasing function for a given patient to predict the future probability of developing T2DM. The model is workable but still has many limitations to overcome. Finally, this dissertation demonstrates some risks factors which are underestimated and are worthy for further research to revise the current T2DM screening guideline. The results were still preliminary. I need to collaborate with an epidemiologist and other fields to verify the findings. In the future, the methods for building a T2DM prediction model can also be used for other prediction models of chronic conditions

Nutrition for Musculoskeletal Health

The maintenance of optimal musculoskeletal health is increasingly recognized as a key element for promoting overall health and fostering independent living in advanced age. Growing evidence indicates that nutrition, together with an active lifestyle, plays a central role in supporting musculoskeletal health both aging and in the setting of specific disease conditions. This Special Issue of Nutrients, entitled “Nutrition for Musculoskeletal Health”, includes original research and review contributions highlighting the relevance of nutrition to musculoskeletal health during aging and in the context of specific diseases. The overarching theme of the Special Issue is addressed through a multidisciplinary set of articles embracing clinical, basic science, and translational studies