REGISTRATION AND SEGMENTATION OF BRAIN MR IMAGES FROM ELDERLY INDIVIDUALS

Quantitative analysis of the MRI structural and functional images is a fundamental component in the assessment of brain anatomical abnormalities, in mapping functional activation onto human anatomy, in longitudinal evaluation of disease progression, and in computer-assisted neurosurgery or surgical planning. Image registration and segmentation is central in analyzing structural and functional MR brain images. However, due to increased variability in brain morphology and age-related atrophy, traditional methods for image registration and segmentation are not suitable for analyzing MR brain images from elderly individuals. The overall goal of this dissertation is to develop algorithms to improve the registration and segmentation accuracy in the geriatric population. The specific aims of this work includes 1) to implement a fully deformable registration pipeline to allow a higher degree of spatial deformation and produce more accurate deformation field, 2) to propose and validate an optimum template selection method for atlas-based segmentation, 3) to propose and validate a multi-template strategy for image normalization, which characterizes brain structural variations in the elderly, 4) to develop an automated segmentation and localization method to access white matter integrity (WMH) in the elderly population, and finally 5) to study the default-mode network (DMN) connectivity and white matter hyperintensity in late-life depression (LLD) with the developed registration and segmentation methods. Through a series of experiments, we have shown that the deformable registration pipeline and the template selection strategies lead to improved accuracy in the brain MR image registration and segmentation, and the automated WMH segmentation and localization method provides more specific and more accurate information about volume and spatial distribution of WMH than traditional visual grading methods. Using the developed methods, our clinical study provides evidence for altered DMN connectivity in LLD. The correlation between WMH volume and DMN connectivity emphasizes the role of vascular changes in LLD's etiopathogenesis

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Effective Brain Connectivity for fNIRS with Fuzzy Cognitive Maps in Neuroergonomics

Effective connectivity (EC) amongst functional near-infrared spectroscopy (fNIRS) signals is a quantitative measure of the strength of influence between brain activity associated with different regions of the brain. Evidently, accurate deciphering of EC gives further insight into the understanding of the intricately complex nature of neuronal interactions in the human brain. This work presents a novel approach to estimate EC in the human brain signals using enhanced fuzzy cognitive maps (FCMs). The proposed method presents a regularized methodology of FCMs, called effective FCMs (E-FCMs), with improved accuracy for predicting EC between real, and synthetic fNIRS signals. Essentially, the revisions made in the FCM methodology include a more powerful prediction formula for FCM combined with independent tuning of the transformation function parameter. A comparison of EC in fNIRS signals obtained from E-FCM with that obtained from standard FCM, general linear model (GLM) parameters that power Dynamic Causal Modelling (DCM), and Granger Causality (GC) manifests the greater prowess of the proposed E-FCM over the aforementioned methods. For real fNIRS data, an empirical investigation is also made to gain an insight into the role of oxyhemoglobin and deoxyhemoglobin (oxy-Hb, deoxy-Hb) in representing the cognitive activity. We believe this work has profound implications for neuroergonomics research communities

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

The Human Connectome Project's neuroimaging approach

Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease

Construction of embedded fMRI resting state functional connectivity networks using manifold learning

We construct embedded functional connectivity networks (FCN) from benchmark resting-state functional magnetic resonance imaging (rsfMRI) data acquired from patients with schizophrenia and healthy controls based on linear and nonlinear manifold learning algorithms, namely, Multidimensional Scaling (MDS), Isometric Feature Mapping (ISOMAP) and Diffusion Maps. Furthermore, based on key global graph-theoretical properties of the embedded FCN, we compare their classification potential using machine learning techniques. We also assess the performance of two metrics that are widely used for the construction of FCN from fMRI, namely the Euclidean distance and the lagged cross-correlation metric. We show that the FCN constructed with Diffusion Maps and the lagged cross-correlation metric outperform the other combinations

Automatic Autism Spectrum Disorder Detection Using Artificial Intelligence Methods with MRI Neuroimaging: A Review

Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, the process of diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist the specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We conclude by suggesting future approaches to detecting ASDs using AI techniques and MRI neuroimaging

Dimensionality reduction and unsupervised learning techniques applied to clinical psychiatric and neuroimaging phenotypes

Unsupervised learning and other multivariate analysis techniques are increasingly recognized in neuropsychiatric research. Here, finite mixture models and random forests were applied to clinical observations of patients with major depression to detect and validate treatment response subgroups. Further, independent component analysis and agglomerative hierarchical clustering were combined to build a brain parcellation solely on structural covariance information of magnetic resonance brain images. Übersetzte Kurzfassung: Unüberwachtes Lernen und andere multivariate Analyseverfahren werden zunehmend auf neuropsychiatrische Fragestellungen angewendet. Finite mixture Modelle wurden auf klinische Skalen von Patienten mit schwerer Depression appliziert, um Therapieantwortklassen zu bilden und mit Random Forests zu validieren. Unabhängigkeitsanalysen und agglomeratives hierarchisches Clustering wurden kombiniert, um die strukturelle Kovarianz von Magnetresonanz­tomographie-Bildern für eine Hirnparzellierung zu nutzen

Normative model for the diagnosis of neuropsychiatric disorders using deep learning methods

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2021The diagnosis of neuropsychiatric disorders (NPDs) is still exclusively dependent on the analysis of the signs and symptoms of the patients since there are no biomarkers useful for clinical practice. Considering that several signs and symptoms are shared among different NPDs, the diagnosis is sometimes incorrect. Therefore, therapeutic approaches do not always succeed, which has an impact on the quality of life of neuropsychiatric patients. Furthermore, NPDs have a global economic and demographic impact. For this reason, technological solutions, such as DL, have been researched for the optimization of diagnosis, in the non-technological field of neuropsychiatry. However, the most promising studies on the diagnosis of NPDs with deep learning (DL) are based on binary classification, which may not be the most adequate approach to deal with the continuous spectrum of NPDs. Here, a DL-based normative model was developed to investigate functional connectivity abnormalities, that may contribute to the development of a novel diagnostic procedure. This method is here used to evaluate how patients deviate from a normal pattern learned by a group of healthy people. To create and evaluate the normative model, resting-state functional magnetic resonance imaging (rs-fMRI) data from three different databases were used. In order to maximise the balance between the amount and the quality of the data, conditions were defined to restrict the variability of the scan parameters. Subsequently, rs-fMRI data were trimmed to the lowest number of time points presented in the sample (150). Then, standard preprocessing steps were performed, including removal of the first 4 volumes of functional data, motion correction, spatial smoothing, and high pass filtering. Single-session independent component analysis (ICA) was run, and the FSL-FIX tool was used to clean noise and artefacts. The functional images were then registered to the T1-weighted brain extracted structural images, and finally to the Montreal Neurosciences Institute 152 standard space. Dual regression was applied using fourteen resting-state functional brain networks (FBN) previously identified in the literature. The Pearson’s correlation coefficient between the extracted blood oxygen level-dependent (BOLD) time series of each FBN was calculated, and a 14x14 network connectivity matrix was generated for each subject. The second part of the project consisted of the creation and optimization of a normative model. The normative model consisted of an autoencoder (AE) with three hidden layers. The AE was trained only in healthy subjects and was tested in both healthy subjects and neuropsychiatric patients, including schizophrenia (SCZ), bipolar disorder (BD), and attention deficit hyperactivity disorder (ADHD) patients. The hypothesis was that the model would “fail” on reconstructing data from neuropsychiatric patients. To evaluate the model performance, graph theory metrics were applied. Besides, the mean squared error was calculated for each feature (correlation between pairs of FBN) to evaluate which regions were worse reconstructed for each group of subjects. The pipeline for NPDs was tested for a SCZ case study, with the addition of a clustering algorithm. The results of this dissertation revealed that the proposed pipeline was able to identify patterns of functional connectivity abnormality that characterize different NPDs. Moreover, the results found for the two SCZ groups of patients were similar, which demonstrated that the normative model here presented was also generalizable. However, the group-level differences did not withstand individual-level analysis, implying that NPDs are highly heterogeneous. These findings support the idea that a precision-based medical approach, focusing on the specific functional network changes of individual patients, may be more beneficial than the traditional group-based diagnostic classification. A personalised diagnosis would allow for personalised therapy, improving the quality of life of neuropsychiatric patients

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions