Tensor Analysis and Fusion of Multimodal Brain Images

Current high-throughput data acquisition technologies probe dynamical systems with different imaging modalities, generating massive data sets at different spatial and temporal resolutions posing challenging problems in multimodal data fusion. A case in point is the attempt to parse out the brain structures and networks that underpin human cognitive processes by analysis of different neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the multimodal, multi-scale nature of neuroimaging data is well reflected by a multi-way (tensor) structure where the underlying processes can be summarized by a relatively small number of components or "atoms". We introduce Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network notation in order to analyze these models. These diagrams not only clarify matrix and tensor EEG and fMRI time/frequency analysis and inverse problems, but also help understand multimodal fusion via Multiway Partial Least Squares and Coupled Matrix-Tensor Factorization. We show here, for the first time, that Granger causal analysis of brain networks is a tensor regression problem, thus allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI recordings shows the potential of the methods and suggests their use in other scientific domains.Comment: 23 pages, 15 figures, submitted to Proceedings of the IEE

Neural Connectivity with Hidden Gaussian Graphical State-Model

The noninvasive procedures for neural connectivity are under questioning. Theoretical models sustain that the electromagnetic field registered at external sensors is elicited by currents at neural space. Nevertheless, what we observe at the sensor space is a superposition of projected fields, from the whole gray-matter. This is the reason for a major pitfall of noninvasive Electrophysiology methods: distorted reconstruction of neural activity and its connectivity or leakage. It has been proven that current methods produce incorrect connectomes. Somewhat related to the incorrect connectivity modelling, they disregard either Systems Theory and Bayesian Information Theory. We introduce a new formalism that attains for it, Hidden Gaussian Graphical State-Model (HIGGS). A neural Gaussian Graphical Model (GGM) hidden by the observation equation of Magneto-encephalographic (MEEG) signals. HIGGS is equivalent to a frequency domain Linear State Space Model (LSSM) but with sparse connectivity prior. The mathematical contribution here is the theory for high-dimensional and frequency-domain HIGGS solvers. We demonstrate that HIGGS can attenuate the leakage effect in the most critical case: the distortion EEG signal due to head volume conduction heterogeneities. Its application in EEG is illustrated with retrieved connectivity patterns from human Steady State Visual Evoked Potentials (SSVEP). We provide for the first time confirmatory evidence for noninvasive procedures of neural connectivity: concurrent EEG and Electrocorticography (ECoG) recordings on monkey. Open source packages are freely available online, to reproduce the results presented in this paper and to analyze external MEEG databases

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

Frameworks to Investigate Robustness and Disease Characterization/Prediction Utility of Time-Varying Functional Connectivity State Profiles of the Human Brain at Rest

Neuroimaging technologies aim at delineating the highly complex structural and functional organization of the human brain. In recent years, several unimodal as well as multimodal analyses of structural MRI (sMRI) and functional MRI (fMRI) neuroimaging modalities, leveraging advanced signal processing and machine learning based feature extraction algorithms, have opened new avenues in diagnosis of complex brain syndromes and neurocognitive disorders. Generically regarding these neuroimaging modalities as filtered, complimentary insights of brain’s anatomical and functional organization, multimodal data fusion efforts could enable more comprehensive mapping of brain structure and function. Large scale functional organization of the brain is often studied by viewing the brain as a complex, integrative network composed of spatially distributed, but functionally interacting, sub-networks that continually share and process information. Such whole-brain functional interactions, also referred to as patterns of functional connectivity (FC), are typically examined as levels of synchronous co-activation in the different functional networks of the brain. More recently, there has been a major paradigm shift from measuring the whole-brain FC in an oversimplified, time-averaged manner to additional exploration of time-varying mechanisms to identify the recurring, transient brain configurations or brain states, referred to as time-varying FC state profiles in this dissertation. Notably, prior studies based on time-varying FC approaches have made use of these relatively lower dimensional fMRI features to characterize pathophysiology and have also been reported to relate to demographic characterization, consciousness levels and cognition. In this dissertation, we corroborate the efficacy of time-varying FC state profiles of the human brain at rest by implementing statistical frameworks to evaluate their robustness and statistical significance through an in-depth, novel evaluation on multiple, independent partitions of a very large rest-fMRI dataset, as well as extensive validation testing on surrogate rest-fMRI datasets. In the following, we present a novel data-driven, blind source separation based multimodal (sMRI-fMRI) data fusion framework that uses the time-varying FC state profiles as features from the fMRI modality to characterize diseased brain conditions and substantiate brain structure-function relationships. Finally, we present a novel data-driven, deep learning based multimodal (sMRI-fMRI) data fusion framework that examines the degree of diagnostic and prognostic performance improvement based on time-varying FC state profiles as features from the fMRI modality. The approaches developed and tested in this dissertation evince high levels of robustness and highlight the utility of time-varying FC state profiles as potential biomarkers to characterize, diagnose and predict diseased brain conditions. As such, the findings in this work argue in favor of the view of FC investigations of the brain that are centered on time-varying FC approaches, and also highlight the benefits of combining multiple neuroimaging data modalities via data fusion

Multimodal Data Fusion: An Overview of Methods, Challenges and Prospects

International audienceIn various disciplines, information about the same phenomenon can be acquired from different types of detectors, at different conditions, in multiple experiments or subjects, among others. We use the term "modality" for each such acquisition framework. Due to the rich characteristics of natural phenomena, it is rare that a single modality provides complete knowledge of the phenomenon of interest. The increasing availability of several modalities reporting on the same system introduces new degrees of freedom, which raise questions beyond those related to exploiting each modality separately. As we argue, many of these questions, or "challenges" , are common to multiple domains. This paper deals with two key questions: "why we need data fusion" and "how we perform it". The first question is motivated by numerous examples in science and technology, followed by a mathematical framework that showcases some of the benefits that data fusion provides. In order to address the second question, "diversity" is introduced as a key concept, and a number of data-driven solutions based on matrix and tensor decompositions are discussed, emphasizing how they account for diversity across the datasets. The aim of this paper is to provide the reader, regardless of his or her community of origin, with a taste of the vastness of the field, the prospects and opportunities that it holds

Scalable Machine Learning Methods for Massive Biomedical Data Analysis.

Modern data acquisition techniques have enabled biomedical researchers to collect and analyze datasets of substantial size and complexity. The massive size of these datasets allows us to comprehensively study the biological system of interest at an unprecedented level of detail, which may lead to the discovery of clinically relevant biomarkers. Nonetheless, the dimensionality of these datasets presents critical computational and statistical challenges, as traditional statistical methods break down when the number of predictors dominates the number of observations, a setting frequently encountered in biomedical data analysis. This difficulty is compounded by the fact that biological data tend to be noisy and often possess complex correlation patterns among the predictors. The central goal of this dissertation is to develop a computationally tractable machine learning framework that allows us to extract scientifically meaningful information from these massive and highly complex biomedical datasets. We motivate the scope of our study by considering two important problems with clinical relevance: (1) uncertainty analysis for biomedical image registration, and (2) psychiatric disease prediction based on functional connectomes, which are high dimensional correlation maps generated from resting state functional MRI.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111354/1/takanori_1.pd