Perspective Chapter: Artificial Intelligence in Multiple Sclerosis

In recent times, the words artificial intelligence, machine learning, and deep learning have been making a lot of buzz in different domains and especially in the healthcare sector. In disease areas like multiple sclerosis (MS), these intelligent systems have great potential in aiding the detection and prediction of disease progression and disability, identification of disease subtypes, monitoring, treatment, and novel drug-target identification. The different imaging techniques used to date in multiple sclerosis, various algorithms such as convolutional neural network, Support Vector Machine, long short-term memory networks, JAYA, Random Forest, Naive Bayesian, Sustain, DeepDTnet, and DTINet used in the various domains of multiple sclerosis are explored, along with used cases. Hence it is important for healthcare professionals to have knowledge on artificial intelligence for achieving better healthcare outcomes

Applications of machine learning to diagnosis and treatment of neurodegenerative diseases

Globally, there is a huge unmet need for effective treatments for neurodegenerative diseases. The complexity of the molecular mechanisms underlying neuronal degeneration and the heterogeneity of the patient population present massive challenges to the development of early diagnostic tools and effective treatments for these diseases. Machine learning, a subfield of artificial intelligence, is enabling scientists, clinicians and patients to address some of these challenges. In this Review, we discuss how machine learning can aid early diagnosis and interpretation of medical images as well as the discovery and development of new therapies. A unifying theme of the different applications of machine learning is the integration of multiple high-dimensional sources of data, which all provide a different view on disease, and the automated derivation of actionable insights

Building trajectories through clinical data to model disease progression

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Clinical trials are typically conducted over a population within a defined time period in order to illuminate certain characteristics of a health issue or disease process. These cross-sectional studies provide a snapshot of these disease processes over a large number of people but do not allow us to model the temporal nature of disease, which is essential for modeling detailed prognostic predictions. Longitudinal studies, on the other hand, are used to explore how these processes develop over time in a number of people but can be expensive and time-consuming, and many studies only cover a relatively small window within the disease process. This thesis describes the application of intelligent data analysis techniques for extracting information from time series generated by different diseases. The aim of this thesis is to identify intermediate stages in a disease process and sub-categories of the disease exhibiting subtly different symptoms. It explores the use of a bootstrap technique that fits trajectories through the data generating “pseudo time-series”. It addresses issues including: how clinical variables interact as a disease progresses along the trajectories in the data; and how to automatically identify different disease states along these trajectories, as well as the transitions between them. The thesis documents how reliable time-series models can be created from large amounts of historical cross-sectional data and a novel relabling/latent variable approach has enabled the exploration of the temporal nature of disease progression. The proposed algorithms are tested extensively on simulated data and on three real clinical datasets. Finally, a study is carried out to explore whether we can “calibrate” pseudo time-series models with real longitudinal data in order to improve them. Plausible directions for future research are discussed at the end of the thesis

Unsupervised Behaviour Analysis and Magnification (uBAM) using Deep Learning

Motor behaviour analysis is essential to biomedical research and clinical diagnostics as it provides a non-invasive strategy for identifying motor impairment and its change caused by interventions. State-of-the-art instrumented movement analysis is time- and cost-intensive, since it requires placing physical or virtual markers. Besides the effort required for marking keypoints or annotations necessary for training or finetuning a detector, users need to know the interesting behaviour beforehand to provide meaningful keypoints. We introduce unsupervised behaviour analysis and magnification (uBAM), an automatic deep learning algorithm for analysing behaviour by discovering and magnifying deviations. A central aspect is unsupervised learning of posture and behaviour representations to enable an objective comparison of movement. Besides discovering and quantifying deviations in behaviour, we also propose a generative model for visually magnifying subtle behaviour differences directly in a video without requiring a detour via keypoints or annotations. Essential for this magnification of deviations even across different individuals is a disentangling of appearance and behaviour. Evaluations on rodents and human patients with neurological diseases demonstrate the wide applicability of our approach. Moreover, combining optogenetic stimulation with our unsupervised behaviour analysis shows its suitability as a non-invasive diagnostic tool correlating function to brain plasticity.Comment: Published in Nature Machine Intelligence (2021), https://rdcu.be/ch6p

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig

Early Detection of Neurodegenerative Diseases from Bio-Signals: A Machine Learning Approach

Given the fact that people, especially in advanced countries, are living longer due to the advancements in medical sciences which resulted in the prevalence of age-related diseases like Alzheimer’s and dementia. The occurrence of such diseases continues to increase and ultimately the cost of caring for these groups will become unsustainable. Addressing this issue has reached a critical point and failing to provide a strategic way forward will negatively affect patients, national health services and society as a whole.Three distinctive development stages of neurodegenerative diseases (Retrogenesis, Cognitive Impairment and Gait Impairment) motivated me to divide this research work into two main parts. To fully achieve the purpose of early detection/diagnosis, I aimed at analysing the gait signals as well as EEG signals, separately, as both of these signals severely get affected by any neurological disease.The first part of this research work focuses on the discrimination analysis of gait signals of different neurodegenerative diseases (Parkinson’s, Huntington, and Amyotrophic Lateral Sclerosis) and also of control subjects. This involves relevant feature extraction, solving the issues of imbalanced datasets and missing entries and lastly classification of multiclass datasets. For the classification and discrimination of gait signals, eleven (11) classifiers are selected representing linear, non-linear and Bayes normal classification techniques. Results revealed that three classifiers have provided us with higher accuracy rate which are UDC, LDC and PARZEN with 65%, 62.5% and 60% accuracy, respectively. Further, I proposed and developed a new classifier fusion strategy that combined classification algorithms with combining rules (voting, product, mean, median, maximum and minimum). It generates better results and classifies subjects more accurately than base-level classifiers.The last part of this research work is based on the rectification and computation of EEG signals of mild Alzheimer’s disease patients and control subjects. To detect the perturbation in EEG signals of Alzheimer’s patients, three neural synchrony measurement techniques; phase synchrony, magnitude squared coherence and cross correlation are applied on three different databases of mild Alzheimer’s disease (MiAD) patients and healthy subjects. I have compared right and left temporal parts of brain with rest of the brain area (frontal, central and occipital), as temporal regions are relatively the first ones to be affected by Alzheimer’s. Two novel methods are proposed to compute the neural synchronization of the brain; Average synchrony measure and PCA based synchrony measure. These techniques are evaluated for three different datasets of MiAD patients and control subjects using the Wilcoxon ranksum test (Mann-Whitney U test). Results demonstrated that PCA based method helped us to find more significant features that can be used as biomarkers for the early diagnosis of Alzheimer’s

Machine learning for classification and prediction of brain diseases: recent advances and upcoming challenges

International audiencePurpose of review. Machine learning (ML) is an artificial intelligence technique that allows computers to perform a task without being explicitly programmed. ML can be used to assist diagnosis and prognosis of brain disorders. While the earliest papers date from more than ten years ago, research increases at a very fast pace. Recent findings. Recent works using ML for diagnosis have moved from classification of a given disease versus controls to differential diagnosis. Intense research has been devoted to the prediction of the future patient state. While a lot of earlier works focused on neuroimaging as data source, the current trend is on the integration of multimodal. In terms of targeted diseases, dementia remains dominant, but approaches have been developed for a wide variety of neurological and psychiatric diseases. Summary. ML is extremely promising for assisting diagnosis and prognosis in brain disorders. Nevertheless, we argue that key challenges remain to be addressed by the community for bringing these tools in clinical routine: good practices regarding validation and reproducible research need to be more widely adopted; extensive generalization studies are required; interpretable models are needed to overcome the limitations of black-box approaches

The Value of Seizure Semiology in Epilepsy Surgery: Epileptogenic-Zone Localisation in Presurgical Patients using Machine Learning and Semiology Visualisation Tool

Background Eight million individuals have focal drug resistant epilepsy worldwide. If their epileptogenic focus is identified and resected, they may become seizure-free and experience significant improvements in quality of life. However, seizure-freedom occurs in less than half of surgical resections. Seizure semiology - the signs and symptoms during a seizure - along with brain imaging and electroencephalography (EEG) are amongst the mainstays of seizure localisation. Although there have been advances in algorithmic identification of abnormalities on EEG and imaging, semiological analysis has remained more subjective. The primary objective of this research was to investigate the localising value of clinician-identified semiology, and secondarily to improve personalised prognostication for epilepsy surgery. Methods I data mined retrospective hospital records to link semiology to outcomes. I trained machine learning models to predict temporal lobe epilepsy (TLE) and determine the value of semiology compared to a benchmark of hippocampal sclerosis (HS). Due to the hospital dataset being relatively small, we also collected data from a systematic review of the literature to curate an open-access Semio2Brain database. We built the Semiology-to-Brain Visualisation Tool (SVT) on this database and retrospectively validated SVT in two separate groups of randomly selected patients and individuals with frontal lobe epilepsy. Separately, a systematic review of multimodal prognostic features of epilepsy surgery was undertaken. The concept of a semiological connectome was devised and compared to structural connectivity to investigate probabilistic propagation and semiology generation. Results Although a (non-chronological) list of patients’ semiologies did not improve localisation beyond the initial semiology, the list of semiology added value when combined with an imaging feature. The absolute added value of semiology in a support vector classifier in diagnosing TLE, compared to HS, was 25%. Semiology was however unable to predict postsurgical outcomes. To help future prognostic models, a list of essential multimodal prognostic features for epilepsy surgery were extracted from meta-analyses and a structural causal model proposed. Semio2Brain consists of over 13000 semiological datapoints from 4643 patients across 309 studies and uniquely enabled a Bayesian approach to localisation to mitigate TLE publication bias. SVT performed well in a retrospective validation, matching the best expert clinician’s localisation scores and exceeding them for lateralisation, and showed modest value in localisation in individuals with frontal lobe epilepsy (FLE). There was a significant correlation between the number of connecting fibres between brain regions and the seizure semiologies that can arise from these regions. Conclusions Semiology is valuable in localisation, but multimodal concordance is more valuable and highly prognostic. SVT could be suitable for use in multimodal models to predict the seizure focus